The Tinnitus Retraining Therapy Trial (TRTT): study protocol for a randomized controlled

trial
Abstract
Background:
Subjective tinnitus is the perception of sound in the absence of a corresponding external
sound for which there is no known medical etiology. For a minority of individuals with
tinnitus, the condition impacts their ability to lead a normal lifestyle and is severely
debilitating. There is no known cure for tinnitus, so current therapy focuses on reducing the
effect of tinnitus on the patients quality of life. Tinnitus retraining therapy (TRT) uses
nonpsychiatric tinnitus-specific educational counseling and sound therapy in a habituationbased protocol to reduce the patients tinnitus evoked negative reaction to, and awareness of,
the tinnitus, with the ultimate goal of reducing the tinnitus impact on the patients quality of
life. Some studies support the efficacy of TRT, but no trial to date has compared TRT with
the current standard of care or evaluated the separate contributions of TRT counseling and
sound therapy. The Tinnitus Retraining Therapy Trial (TRTT) is a randomized, double-blind,
placebo controlled, multicenter trial for individuals with intolerable tinnitus.
Methods/design:
The TRTT is enrolling activeduty and retired military personnel and their dependents with
functionally adequate hearing sensitivity and severe tinnitus at US Air Force, Navy, and Army
medical centers. Eligible study participants are randomized to TRT, partial TRT, or standard
care to determine the efficacy of TRT and its components (TRT counseling and sound
therapy). The primary outcome is change in score on the Tinnitus Questionnaire assessed
longitudinally between baseline and follow up (3, 6, 12, and 18 months following
treatment). Secondary outcomes include subscale score changes in the Tinnitus Questionnaire,
overall and subscale score changes in the Tinnitus Functional Index and Tinnitus Handicap
Inventory, and change in the visual analog scale of the TRT Interview Form. Audiological
outcomes include tinnitus pitch and loudness match and measures of loudness discomfort levels.
The incidence of depression as a safety measure is assessed at each visit using the Beck
Depression Inventory Fast Screen.
Trial registration: Clinicaltrials.gov NCT01177137.
Keywords: Randomized clinical trial, Tinnitus, Tinnitus retraining therapy

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Background
Tinnitus is the perception of sound in the absence of a corresponding external sound for
which there is no apparent cause. The precise mechanisms underlying subjective
tinnitus are currently unknown. Almost everyone experiences some degree of tinnitus at
some time, including sensations of ringing, buzzing, whistling, or hissing. The majority
of persons experiencing tinnitus do not report undue distress associated with the
tinnitus or require professional help. The prevalence of continuous subjective tinnitus
among adults ranges from 10.1 to 14.5%, but only about 20% of these individuals require professional help for the treatment of their tin- nitus. For some of these
individuals, the impact of tinnitus is severely debilitating, impairing their wellbeing
and ability to lead a normal lifestyle.
Currently, there is no reliable means of curing tinnitus at its source. Evidence from
Cochrane reviews of tinnitus treatment trials indicates that no medical or nonmedical
treatment is more effective than placebo in eliminating tinnitus. Consequently, current
efforts to treat tinnitus focus on reducing the effect of tinnitus on health-related quality
of life. Cognitive behavioral therapy, which challenges negative feelings associated with
tinnitus and thus seeks to reduce the patients focus on tinnitus and the corresponding
distress, has some efficacy, as demonstrated in a Cochrane review. Tinnitus retraining
therapy (TRT) also aims to reduce the focus of the individual on his or her tinnitus and
its impact on health related quality of life. Tinnitus retraining therapy involves
nonpsychiatric tinnitusspecific educational counseling and low-level sound therapy to
habituate the patients associated negative emotional reactions (for example, annoyance,
or anxiety) to tinnitus, the perception of tinnitus (awareness) and, ultimately, the impact
of the tinnitus on the patients life.
Tinnitus retraining therapy is based on a neurophysiological model of tinnitus . The
model hypothesizes that the distress associated with tinnitus arises from abnormal
subconscious nonauditory mechanisms, mediated primarily by the limbic and
autonomic nervous systems. Preliminary evidence from various uncontrolled studies of
individuals, who received full or partial TRT as part of their treatment for tinnitus,
consistently supports the therapeutic benefits of the full TRT protocol. When the TRT
protocol is closely followed, typical rates of clinical success, as judged by a minimum
of 20% im- provement in two or more impact-on-life scales, ap- proach or exceed 80%
improvement. A recent Cochrane systematic review of TRT found only one randomized
trial that adhered to the TRT protocol as developed by Jastreboff and Hazell . This trial
com- pared TRT with a tinnitus masking intervention. The investigators found that
both treatments were efficacious in treating tinnitus over a treatment period of 18
months, but that TRT resulted in greater im- provement in patients with greater tinnitus
severity at baseline. However, the Cochrane reviewers noted the presence of design
flaws that could have resulted in biased findings. Results from three smaller trials have
subsequently been published. Bauer and Brozoski found that both TRT and general

counseling were effi- cacious in reducing the annoyance and impact of tin- nitus over
18 months, and that the effect size was greater for TRT (1.13) than for general
counseling (0.78). In a second trial [16], a comparison of accept- ance and
commitment therapy with TRT showed that acceptance and commitment therapy
yielded a signifi- cantly larger reduction in tinnitus impact than did TRT at 10 weeks,
6 months, and 18 months of treatment. Lastly, Tyler et al. evaluated masking versus
TRT sound therapy and no sound therapy in study participants provided with an
equivalent to TRT counseling. This trial reported a positive effect of either sound
therapy or masking compared with counseling alone, but had a high proportion of
dropouts in all treatment arms .
Thus, although the current literature provides some support for the efficacy of TRT, no
trial has compared TRT with the current standard of care. The existing tri- als all
compared TRT with a treatment with unknown efficacy. In addition, no trial has
evaluated the separate contributions of the component parts of TRT, specifically
tinnitus-specific educational counseling and sound therapy. To address these gaps, we
are conducting a randomized, placebcontrolled, multicenter trial of TRT, the Tinnitus
Retraining Therapy Trial (TRTT), by com- paring TRT with the current standard of
care in military hospitals, while parsing out the separate effects of TRT counseling and
sound therapy. A full description of the rationale for the TRTT has been published
previously; this paper describes the design and methods used in the trial.
Methods / design
The primary objective of the TRTT is to assess the effi- cacy of TRT as a treatment for
severe tinnitus. Our spe- cific goals are to evaluate the efficacy of TRT and its
component parts in habituating the perceived magnitude (sensation), perception
(awareness), and negative emo- tional reactions (for example, annoyance, anxiety) to
tin- nitus, and to measure TRT treatment effect on the impact of tinnitus on each
participants health-related quality of life.

Recruitment
The TRTT is currently being conducted at US Air Force, Navi, and Army medical centers
with active-duty and retired military personnel and their dependents. Recruit- ment
began in August 2011 at six clinical centers. One center withdrew from recruitment in
January 2013, and two additional Army medical centers are currently under- going

certification to participate as clinical centers. As of 1 September 2014, clinical centers

have enrolled 136 of the planned 228 study participants.
Eligible study participants have subjective annoying tinnitus of at least one years
duration for which there is no identified medical etiology. They have normal hearing
sensitivity of no worse than mild hearing loss through 4,000 Hz that does not require the
use of hearing aids. Eligible participants had not received treatment for their tinnitus
within the previous year. Specific inclusion and exclusion criteria include the following:
Eligibility criteria for TRTT
Kriteria Inklusi

Age 18 or older.
Primary complaint of continuous, chronic subjective tinnitus for at least one year.
Score on the Tinnitus Questionnaire of 40 or more.
Functionally normal hearing sensitivity by audiometric thresholds 30 dB hearing
loss at and below 2000 Hz and 40 dB hearing loss at 4000 Hz.
Able to understand counseling and comprehend and complete English language
questionnaires.
Willing and able to give informed consent.
Exclusion criteria
Predisposing disease with tinnitus symptoms amenable to medical or surgical
intervention.
Clinical treatment for tinnitus within previous year.
Evidence of malingering or exaggeration of tinnitus or hearing symptoms.
Emotional, psychological, or psychiatric condition precluding full participation
or follow-up.
Active involvement in tinnitus-related litigation.
Diagnosis of pulsatile tinnitus, somatosounds, or objective tinnitus (that is,
spontaneous otoacoustic emissions) that could be responsible for the tinnitus
problem.
Brain or head trauma requiring treatment 24 months before randomization.
Inability to complete audiological testing or other testing required by the clinical
trial protocol.
Study candidates must also be willing and able to provide informed consent to
allow determination of eligi- bility and randomization to treatment for the TRTT.
Before entry into the TRTT, eligible candidates must confirm willingness to be
randomized to an assigned treatment.

Interventions of the TRTT

In the TRTT, participants have an equal probability of assignment to one of three
groups:
1. Full TRT, including tinnitus-specific educational counseling and sound therapy
implemented with ear-level sound generators.
2. Partial TRT, including tinnitus-specific educational counseling and sound therapy
implemented with placebo sound generators.
3. Standard care, as administered in military hospitals, based on surveys of clinicians
at participating clinics and guidelines of the American Speech-Language Hearing
Association [19].
Differences between TRT and standard care are itemized in Table 1 and described in
detail below.
Tinnitus-specific educational counseling
Tinnitus specific educational counseling, as implemented in the TRTT, is based on the
general principles and methodology described by Jastreboff and Hazell, which was the
most comprehensive description of the practice of TRT at the time the trial was
designed. The overall goals of TRT counseling are to educate the participant about his
or her tinnitus condition, initiate tinnitus habituation, and, ultimately, neutralize the
par- ticipants negative emotional associations with his or her tinnitus. The TRT has
two primary subgoals:
(1) habituation of tinnitus-evoked negative reaction (for example, annoyance, anxiety,
or panic related to tinnitus) and
(2) habituation of the perception (awareness of tinnitus). Negative emotional reactions
arise from distress induced by tinnitus; TRT counseling aims to provide information to
reframe (that is, demystify) the participants conscious beliefs and begin to neutralize
the participants negative emotional associations with the tinnitus condition,
facilitating habituation of the re- action. Habituation of the perception of the tinnitus
signal often occurs after a sufficient level of habituation of the reaction is achieved,
and this phase of treatment is facilitated by sound therapy.
The components of the initial TRT counseling session include the following:
Explanation of the results of the audiological/ tinnitus/hyperacusis clinical
evaluation, with an emphasis on the relation of the tinnitus to the clinical
findings.

 Description of the anatomy and physiology of the normal and impaired auditory
system, noting that

Table 1 Comparison of tinnitus retraining therapy and standard care in the TRTT
Topic or concept

Tinnitus retraining therapy (tinnitus counseling and

sound therapy)

Goal of counseling

Introduce the concept of habituation to facilitate

habituation of reaction and secondly, habituation of perception. The
goal is for the participant to move to a state where tinnitus is no
longer an issue.

Short-term goals

Reframe the way the participant views the tinnitus problem by

understanding what it is and what it is not; neutralize negative
emotional associations by understanding the mechanisms that
provoke the emotional reaction to the tinnitus.

Standard care
Reduce negative cognitive, affective, physical and behavioral reactions to tinnitus; improve
the participants wellbeing and quality of life.
Empathize with and validate the participants feelings, provide reassurance, promote self-efficacy
and engage participant in tinnitus management.
Baseline interview and factors that exacerbate tinnitus

Description of the anatomy and physiology of the normal and impaired auditory system

Processing at the level of the brain

Review completed TRT Interview Form, which informs counselor about impact of tinnitus or
decreased sound tolerance on such activities as concentration, sleep, quiet recreational activities,
work, restaurant use, sports, concert attendance, or socializing. This information is then discussed
during counseling and at follow-up appointments.

Explain structures of outer, middle, and inner ear with special attention to the cochlear
structures, function of inner and outer hair cells, and afferent and efferent nerve fibers, using
three-dimensional model of an ear, diagrams, and photos. Emphasize that hearing is perceived
at the brain, not at the ear, which serves only as a transformer, changing mechanical into
electrochemical energy that the brain processes as sound.
Explain that the cortical area of the brain is responsible for the perception of sound, with
monitoring by at least five pre-cortical or subconscious lower levels to filter out irrelevant
sounds and enhance new or dangerous signals based on personal characteristics and situation.
Describe, with examples, ways in which the brain processes signals, including sensory contrast,
selective perception, prioritization, and relationship with tinnitus.
Elicit participants story to identify problem areas.
Describe in general terms outer and inner ear and some description of nerve pathway
Not described.
Explanation of tinnitus Explain key points of Jastreboffs neurophysiological
model of tinnitus, using basic charts, to demonstrate the importance of
the activation of subcortical, limbic and autonomic systems in tinnitus
becoming intrusive.
Sound therapy

Implement sound therapy with sound generators with low-level,

relatively broad-band, sound set to level where sound just begins to
mix with tinnitus sound. Recommend environmental sound and to
avoid silence at all times.

Hearing protection

Recommend use of appropriate noise protection in

hazardous situations, with caveat that participant should not overuse
sound protection. Advise an increase in the volume of the sound
generator in slightly noisier settings or the wearing of muffs over
sound generators to avoid silence.

Sleep

Recommend use of environmental sound throughout the night with

tabletop sound machines or sound pillows that have neutral sound that
can be adjusted to soft, but audible, volume (not television or talk
radio). Discuss etiology of sleep disorders as they relate to tinnitus.

Provide general description, with assurances that tinnitus is common, does not predict hearing
loss, and does not damage health
Recommend environmental sound.
Recommend use of appropriate noise protection in hazardous situations. No recommendation
for or against routine sound protection.
Discuss general guidelines for sleep health and, if necessary for sleep health, recommend
use of environmental sound, if an issue. If not an issue, not discussed.

Concentration

Discuss, if an issue.

Discuss ways to shift attention,

increase attention span, and
avoid distraction, if an
issue; if not an issue, not
discussed.

Stress

Discuss, if an issue.

Discuss
methods
to
facilitate relaxation, if an
issue; if not an issue, no

Discussion of the role of the central auditory system and higher cortical processes
to interpret an auditory signal and how this processing relates to the participants
tinnitus perception.
Description of the Jastreboff neurophysiological model of tinnitus [6], which is the
centerpiece and focus of TRT counseling in informing the participant about the
conscious and subconscious processes involved in the generation and habituation of
the tinnitus. These key processes and components of the model as used in the TRTT
were summarized by Formby and Scherer [18], and considered in depth by
Jastreboff and Hazell [20].
Setting goals with and for the individual participant, by discussing progress made
towards habituation without trying to control or actively monitor the process.
Participants are counseled individually or with family members. The study audiologist
uses a standardized flipchart and visual aids during the TRT counseling ses- sion to
illustrate and explain the participants audio- logical/tinnitus/hyperacusis results,
auditory anatomy and physiology, how the physiological processes relate to tinnitus,
the Jastreboff model of tinnitus, and other key concepts of TRT. The counseling
audiologist also completes a checklist to ensure practitioner fidelity to the TRTT
treatment protocol for tinnitus-specific edu- cational counseling. In the initial TRT
counseling ses- sion, which lasts for approximately two hours, the audiologist presents
information designed to help the participant change the way in which he or she views
his or her tinnitus or decreased sound tolerance (hyperacu- sis), addresses the
individual participants concerns, and recommends strategies to help the participant
achieve the long-term goal of habituation to the tinnitus. Suffi- cient time is allowed to
answer the participants ques- tions and to ensure that he or she understands all
information presented, including the treatment goal of reducing the impact of tinnitus
and, if present, manage- ment of decreased sound tolerance, in his or her life.
Follow-up contacts with participants receiving tinnitus- specific educational
counseling in the TRTT are held at a second treatment visit one month following the
initial counseling session and at 3, 6, 12, and 18 months at the clinical center. Follow-

up sessions vary in length from 15 minutes to an hour, depending on the individual

par- ticipants needs; audiologists reinforce topics covered in the initial TRT
counseling session and discuss results of follow-up interviews and tests.
Sound therapy
Sound therapy was also implemented for TRT following the basic principles and
methodology outlined by Jastreboff and Hazell. An integral part of TRT, sound therapy
aims to facilitate habituation of the perception or awareness of the tinnitus signal by
decreasing the contrast between the tinnitus signal and background sounds. Sound
therapy is believed to decrease the perception of the tinnitus signal by reducing the
gain within the auditory pathways, which further facilitates habituation of the
awareness of the tinnitus signal. Sound therapy for TRT may be implemented in any
form that achieves an enriched sound environment. The most direct, consistent, and
convenient strategy for implementing sound therapy for tinnitus participants with little
or no hearing loss is the use of a low level, relatively broadband, neutral sound,
produced by opencanal bilateral earlevel sound generators. This approach allows sound
therapy from the sound generators to be supplemented with environmental sound. We
have chosen this method of implementing sound ther- apy for the TRTT because it
allows us to standardize the sound therapy administered and to isolate sound therapy
by comparing participants using conventional and placebo sound generators.
In the TRTT, all participants are in TRT Category 1, indicating tinnitus of high
severity and no other significant hearing problems; Category 3, indicating the presence
of hyperacusis; or Category 4, with hyperacusis as the dominant complaint and
exacerbation of symptoms for a prolonged period of time. For the TRTT, hyperacusis
was not an exclusion criterion, but a prospective participant with severely debilitating
hyperacusis could be excluded at the discretion of the study audiologist if he or she
believed that sound therapy was essential for managing the hyperacusis, thus
forestalling assignment of the prospective participant to standard car
The TRTT is using a digital equivalent sound generator of the Tranquil model,
manufactured by General Hearing Instruments, Inc.. Using these sound generators
allows standardization of sound therapy across participants and provides the
opportunity to achieve a double blind placebo for sound therapy in the TRTT. General
Hearing Instruments, Inc., provide both conventional and placebo sound generators
for the TRTT.
The sound generators include data logging capability to monitor sound therapy use
and compliance by the study participant, and sound level exposure to determine the
nature of the primary sound exposure (that is, environmental sound or sound from the
sound generators) at any point in time. The sound generator is housed in either a
behind- the-ear or an in the ear device, both of which offer adjustment of the output
volume to a zero (fully quiet) noise floor. Placebo sound generators have a physical

appear- ance identical to the conventional instrument so that neither study personnel nor
study participants are aware of which sound treatment the participant is receiving. The
sound output of the placebo device is designed to be identical to the conventional
device upon initial insertion into the outer ear, but after the first 40 minutes of use, the
level of sound gradually fades to silence. Double-blinding of the study audiologist and
study participant is made possible by a novel re-setting feature of the sound generators.
Specifically, the placebo device re-sets within 3 seconds to the full output level, as set at
the beginning of initial use, whenever the device is removed from the ear. Thus, if either
the study audiologist or study participant rechecks the placebo output sound level, it
will be heard again at the same level as was set initially and the decay process will
begin anew. This decaying auditory process of the placebo sound generator output
mimics normal auditory per- ceptual adaptation to the sea-shell like noise emitted by
both the conventional and placebo sound generators. The expectation of this normal
perceptual adaptation to the noise is crucial for the success of the placebo sound
generator, and reinforced by instructions to all study participants assigned to sound
therapy using sound generators.
Fitting and activation of sound generators takes place after the TRT counseling
session, and typically requires about one hour. This treatment step includes instruction
to the participant on use of and care for the instruments, correct volume settings,
schedule of use, and insertion and removal of instruments. The instrument volume is
set using programmable software. The audiologist and study participant work together
initially to set the sound generator volume for the ear with the most troublesome
tinnitus. Then the volume is set for the opposite ear, aiming to match the output of both
ears to achieve equal loudness just below the mixing point. In the TRTT, the mixing
point is defined as that volume setting at which the noise from the sound generators
just starts to mix or blend with the participants most bothersome tinnitus sound. The
noise from the sound generator should not change the characteristic of the tinnitus, be
annoying, or mask the tinnitus. Participants are also instructed not to set the volume of
the sound generator too close to the threshold of hearing when first setting the volume,
to avoid augmentation of the tinnitus percept, which might occur because of the
phenomenon of stochastic resonance. During the fitting session, the audiologist
informs the study participant that the sound generated by the sound generators to
achieve effective sound therapy is typically soft, and the noise may not always be heard,
es- pecially in noisy environments. Study participants have a range of 6 dB for resetting
the output levels of their sound generators, enabling them to adjust the volume for
perceived changes in the loudness of the tinnitus from day to day, to maintain a
constant level of effective sound. The audiologist routinely instructs the participant to
set the volume of the sound generators when they are first inserted into the ears and not
to adjust the sound generators afterwards. Study participants are instructed to use the
sound generator as much as possible (even all day), or at least for a minimum of 8 hours
over the course of the day.

The use of environmental sound enrichment at all times, including when

participants use sound generators, is also strongly recommended during TRT, both
during tinnitus-specific educational counseling and while fitting the sound generators.
Avoidance of silence at all times is a primary tenet of TRT. Exposure to a low level of
envir- onmental sound, using a tabletop sound machine, CD player, sound pillow, or
other device, preferably with a volume control (so that the volume is not set too
low), is emphasized for augmenting sleep when the sound generators are not worn.
Use of a television or radio is discouraged because either can attract the attention of
the participant and impair initial efforts to fall asleep or stay asleep through the night.
Exposure to low-level en- vironmental sound is also recommended during any period
of time when the sound generators cannot be worn.
During the second treatment visit and at all subsequent follow-up visits, the
audiologist re-checks the sound gen- erator volume settings with the study
participant to ensure that the appropriate volume levels are being maintained and
the sound generators are functioning properly. In addition, the study participant
may come to the clinic at any time between visits, to adjust the sound generator
vol- ume setting to maintain the appropriate sound level in re- lation to his or her
tinnitus.
Standard care
The standard care protocol developed for the TRTT is con- sistent with information
typically provided to participants with severe tinnitus at participating military medical
centers and with professional guidelines for tinnitus management, as outlined in the
document Preferred Practice Patterns For the Profession of Audiology, produced by the
American Speech-Language-Hearing Association [19]. Tinnitus man- agement in standard
care is based on the individual par- ticipants complaints, history, audiological evaluation,
and self-assessment. Standard care aims to reduce negative cognitive, affective, physical,
and behavioral reactions to tinnitus and improve the participants wellbeing and healthrelated quality of life. The following topics are ad- dressed during standard care
counseling:

 Cause, source, and audiological significance of tinnitus.

Use of hearing protection in noise.
Use of environmental sounds or sound therapy devices (not including ear-level
sound generators) to reduce tinnitus perception.
Identification of factors that may exacerbate tinnitus.
Adaptive coping behaviors.
Stress reduction.
Strategies to minimize sleep difficulties related to tinnitus.
The audiologist begins standard care by eliciting the participants narrative and
establishing a mutual under- standing of the participants tinnitus problem. The audiologist reiterates effective ways in which the participant has coped with tinnitus in the
past and emphasizes ways to minimize the tinnitus impact in the future. The discussion is tailored to the individuals specific complaints, problem situations, coping
strategies, personal prefer- ences, and feasibility. Specific topics that may be covered
include:
Environmental sounds, including a demonstration of available devices (for
example, CD players with nature sounds, sound pillows), excluding ear-level sound
generators or other programmable sound therapy treatments.
Stress reduction, including a discussion of relaxation exercise programs (for
example, Tai Chi, yoga, meditation, progressive muscle relaxation, and visual
imagery) with handouts and performance of a short relaxation exercise, such as
visual imagery or progressive muscle relaxation.
Sleep, including a review of normal sleep patterns and factors that affect sleeping,
such as stress and emotional upheaval, environmental variables (noise, light,
temperature), irregular schedules, jet lag, medications, caffeine, nicotine, and
alcohol. The audiologist will assist the study participant in
identifying variables that impact his or her specific sleep difficulties and provide
a set of recommenda- tions for enhancing sleep.
Concentration and factors that affect concentration, including noise, temperature,
distractions, lighting, hunger, fatigue, health, boredom, stress, depression, and
tinnitus. The audiologist will recommend various steps to increase concentration
and demonstrate attention-shifting exercises.
Not all standard care topics are covered in detail for
all participants; rather, topics
are selected based on those issues or problems that affect the individual participant.

Reinforcement counseling is conducted one month after the initial treatment session,
to review the specific recom- mendations that were made during the initial counseling
visit and to promote self-efficacy by reinforcing the study participants awareness that
he or she can manage tinnitus by incorporating those recommendations into daily
living. The follow-up counseling session will typically range from 15 to 30 minutes,
with the audiologist emphasizing the importance of the consistent use of
environmental sound devices and recommended coping strategies for problem
situations.
Monitoring treatment adherence
In the TRTT, audiologists are encouraged to perform both TRT and standard care
counseling for a number of rea- sons. Primarily, we wished to avoid a differential
counselor effect that could contribute to the treatment effect in that some audiologists
might be better counselors overall than others. Also, we recognized that there could be
a possible counselor effect in that some audiologists might prefer to deliver TRT
counseling over standard care or vice-versa. Alternatively, an audiologist might be
biased a priori in the belief that TRT counseling or standard care is the su- perior
treatment. Secondly, we required that at least one audiologist remain blinded to the
counseling intervention, that is, the noncounseling audiologist would be blinded and
responsible for measuring follow-up audiological or other outcomes. Accordingly,
because of scheduling issues and the limited number of audiologists available to
partici- pate in the study at some clinics, it was necessary to have all audiologists
trained in both counseling methods. The latter was an important consideration for
military partici- pation in the TRTT. Lastly, if either type of counseling proved
superior, we reasoned that it would be advanta- geous for the audiologists to have been
trained in the superior method so that he or she could offer the coun- seling in his or
her practice subsequent to the comple- tion of the trial.
To maintain the validity of the TRTT, however, it is crit- ical that adherence to
protocol is strictly followed for the counseling components of TRT counseling and
standard

care. Because there is some overlap in the topics covered in the TRT counseling and
standard care (for example, recommendation for exposure to ambient low-level
envir- onmental noise), there is a real possibility of treatment contamination.
Consequently, four procedures were im- plemented to facilitate compliance with the
treatment protocol.
Audiologists must be certified to complete either TRT counseling or standard care
prior to providing counseling for a study participant in the trial. Certification
requires submission of a voice recording that is reviewed and, if acceptable,
approved by the protocol monitor. Audiologists providing unacceptable voice
recordings cannot conduct counseling sessions in the trial.
Audiologists are required to use treatment-specific visual aids during the
counseling session that are matched to TRT counseling or standard care.
Audiologists must complete a checklist during each study TRT counseling or
standard care session by ticking topics covered or discussed in that session.
All treatment sessions are voice recorded. Files generated by voice recorders are
submitted along with the relevant checklist for review for compliance with the
assigned treatment study protocol. Recordings of the first two treatment sessions of
each type of counseling conducted by an individual audiologist are reviewed for
adherence to protocol. If no deficiencies are noted in these sessions, then one
recording from among the next five counseling sessions is randomly selected for
review as long as adherence to the treatment protocol is maintained
by that
audiologist. Nonadherence to the treatment protocol at any one session will be
followed by retraining and subsequent review of the next two sessions conducted by
that audiologist. Continuing noncompliance results in decertification of that
audiologist, who will not be allowed to conduct any further counseling sessions in
the trial.
Randomization
Randomization is stratified by clinical center and occurs in blocks of random multiples
of three in the TRTT. The random order of the allocation assignments for each clinic is
generated using a computer-generated random permu- tation. After final determination
of eligibility, clinic staff accesses the TRTT website to obtain a randomization assignment, designated either TRT or standard care.
Sound generators are identified in the TRTT using se- quential serial numbers, with
conventional or placebo sound generators identified by serial number. Prior to the
study start, General Hearing Instruments, Inc., pro- vided a block of 600 serial
numbers (300 pairs) to the data coordinating center, to identify specific devices to

be used in the TRTT. The data coordinating center randomly designated serial
numbers to be used for con- ventional or placebo sound generators, and provided
General Hearing Instruments, Inc., with a copy of these assignments. General
Hearing Instruments, Inc., then manufactured the standard or placebo sound
generators as specified for each assigned serial number.
At the beginning of the study, the TRTT used behind- the-ear devices. General
Hearing Instruments, Inc., sent a sufficient number of pairs of sound generators to
the data coordinating center to supply clinics with the first six ran- domized
treatment assignments. For assignment to TRT, the data coordinating center placed
the sound generators within a box, matching the serial number of the sound
generators to the sound generator type (standard or pla- cebo) for randomized
treatment assignment (TRT or par- tial TRT). Standard care assignments comprised
a box that contained a sheet of paper noting assignment to standard care. Early in
the trial, it became obvious that for some study participants, the in-use sensor
detection tech- nology for the behind-the-ear devices failed at an un- acceptable rate
for both conventional and placebo sound generators. The decision was made to
move from behind- the-ear sound generators to nonoccluding in-the-ear de- vices.
The data coordinating center continues to send boxed kits to the clinical centers, but
instead of including sound generators in the box, the data coordinating center places
a form in the box for the clinic to use to order sound generators directly from
General Hearing Instru- ments, Inc.; the form includes the serial number for that
assignment. By including the serial number, General Hearing Instruments, Inc., is
notified which type of sound generator (conventional or placebo) to manufacture for
that study participant, while clinic staff remain unaware of the assignment.
Outcomes
The TRTT is using patient-reported outcome question- naires, completed on paper, to
assess tinnitus-specific health-related quality of life, general health-related qual- ity of
life, and relevant psychological measures. All ques- tionnaires are standardized
instruments with well documented psychometric properties. The TRTT also collects
information on audiological measures of tinnitus pitch and loudness match and
loudness discomfort levels. Additionally, the TRTT assesses the presence of depression at each study visit as a possible adverse event.
The TRTT uses three different tinnitus-specific health- related quality of life
measurement tools: the Tinnitus Questionnaire [21]; the Tinnitus Functional Index [22];
and the Tinnitus Handicap Inventory [23]. In addition, the overall impact of tinnitus is
assessed using the ten- point visual analog scale of the TRT Interview Form [24].
Each instrument is administered at baseline and at 3-, 6-, 12-, and 18-month follow-up
visits. The three tinnitus-specific health-related quality of life instruments (Tinnitus
Questionnaire, Tinnitus Functional Index, and Tinnitus Handicap Inventory) are also
administered at 30, 42, and 54 months by mail for study participants agreeing to
extended follow-up, to assess whether any treatment effect is maintained over time.

The primary outcome measure selected for the TRTT is change in score on the
Tinnitus Questionnaire, assessed longitudinally from baseline to the 18-month followup visit. The 52-item Tinnitus Questionnaire features a three- point response scale, five
subscales, and excellent validity and generalizability properties [21]. The subscales: are
psy- chological distress, intrusiveness, hearing difficulties, sleep disturbances, and
somatic complaints. The baseline score of the Tinnitus Questionnaire determines
eligibility (score 40) for the TRTT and provides a value for comparison at follow-up.
The Tinnitus Functional Index is an instrument re- cently developed by a group of
experienced tinnitus in- vestigators funded by the Tinnitus Research Consortium [22]. It
has 25 items and an eight-factor structure, in- cluding intrusiveness, reduced sense of
control, cognitive interference, sleep disturbance, auditory difficulties (re- lated to
tinnitus), relaxation interference, reduced quality of life, and emotional distress. Each
question on the in- strument has a ten-point response scale (ranging from no effect to
extreme effect). The Tinnitus Functional Index has been validated for assessing
responsiveness (that is, changes in outcomes related to treatment).
The Tinnitus Handicap Inventory, developed by Newman et al. [23], consists of 25 items
and has three factors, in- cluding functional, emotional, and catastrophic, evaluated using a
three-point response scale.
The TRTT will also measure the overall treatment ef- fect of the study interventions
using the ten-point visual analog scale of the TRT Interview Form, which asks the study
participant to rate the impact of tinnitus on his or her life from not at all to as much
as you can imagine.
Because tinnitus may affect the ability of study partici- pants to concentrate, the TRTT
is also measuring cogni- tive function with the Digit Symbol Substitution Test [25].
This test assesses the ability of an individual to focus attention on a task. Indirectly, this
measure as- sesses the ability of the study participant to ignore the tinnitus signal while
completing a task requiring atten- tion and psychomotor skill. The Digit Symbol
Substitu- tion Test is administered by study staff at baseline, and at the 6- and 18month visits.
The TRTT collects information using two additional health-related quality of life
instruments, the Hearing Handicap Inventory [26] and the EuroQoL [27]. The Hearing
Handicap Inventory is a ten-item instrument
[26] used in the TRTT to assess the impact of hearing loss on overall and tinnitusrelated health-related quality of life. The EuroQoL consists of five items that assess
difficulty in performing activities of daily living [27]. It uses a three-part Likert scale
and a visual analog scale that ranges from 0 (worst imaginable health) to 100 (best
imaginable health state). The Hearing Handicap In- ventory and the EuroQoL are
completed at baseline and at 6- and 18-months follow-up visits.
The TRTT is administering three psychological instru- ments, the State-Trait Anxiety
Inventory [28], the Posi- tive and Negative Affect Schedule [29], and the Life Events
Checklist [30], to assess personality traits or life events that might be associated with

treatment efficacy. These instruments are administered at baseline and at 6- and 18month follow-up visits. In addition, the TRTT is administering the Beck Depression
Inventory Fast Screen [31] at baseline and all follow-up visits, as a safety screen for
depression.
The State-Trait Anxiety Inventory is a self-report measure of trait anxiety (or anxiety
proneness) and state anxiety (that is, transitory anxiety experienced under specific
conditions). Participants complete both subscales of the State-Trait Anxiety Inventory
at baseline and the state subscale at 6- and 18-month follow-up visits. The Positive
and Negative Affect Schedule con- sists of 20 adjectives describing feelings or
emotions (for example: excited, scared, irritable, nervous), that might change with
treatment benefits. To assess life events that could result in stress and anxiety
impacting wellbeing and possibly treatment efficacy, the TRTT also adminis- ters the
Life Events Checklist.
The Beck Depression Inventory Fast Screen is used as a screen for depression. The
TRTT requires a threshold score of 4 or more, or endorsement (a response of 2 or
3) of suicidal thoughts or wishes, to determine the need for further mental health
evaluation. Repeated measures of the Beck Depression Inventory Fast Screen over
the course of the TRTT will permit study participants to be monitored for the onset
of serious depression as a pos- sible consequence of treatment or other contributing
factors.
Audiological outcomes
Audiological outcomes measured in the TRTT include pure-tone audiometric
thresholds, speech recognition thresholds, tinnitus pitch and loudness match, and loudness discomfort levels. Pure-tone and speech audiometry are used in the TRTT to
evaluate changes in the partici- pants hearing sensitivity and are performed at baseline
and at 6-, 12-, and 18-month follow-up visits. Tinnitus pitch match, which identifies
the frequency or frequency range that most closely matches the pitch of the participants tinnitus, and tinnitus loudness match, which

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matches the intensity of the participants most trouble- some tinnitus, will be performed
at baseline, and at 6-, 12-, and 18-month follow-up visits. Loudness discomfort level is
a measure of the sound level at which an individ- ual first judges the loudness of a
sound to cause discom- fort. Loudness discomfort levels set the functional upper limit
of the listeners dynamic range, that is, the range between the hearing threshold and the
loudest comfort- ably tolerated sound. In the TRTT, loudness discomfort levels are used
to determine whether intolerance to sound (hyperacusis) is abnormal and associated
with the participants tinnitus. If hyperacusis is present, the loudness discomfort levels
are used to determine the steps required to modify the level of sound set in the sound
generators by the audiologist. Loudness discom- fort levels are measured at every study
visit. The audi- ologist performing the audiometric tests for an individual study
participant is blinded to that partici- pants treatment assignment.
Efficacy outcomes
The primary objective of the TRTT is to assess the efficacy of TRT, achieved
through TRT counseling and sound ther- apy (provided by conventional sound
generators), as a treatment for severe debilitating tinnitus. The primary outcome to
be measured in the TRTT is the difference in score on the Tinnitus Questionnaire
between baseline and follow-up, assessed longitudinally, after 3, 6, 12, and 18
months of treatment. The TRTT also will investigate the efficacy of sound therapy
by comparing Tinnitus Questionnaire scores of participants assigned to conventional sound generators with those assigned to placebo sound generators, where
both groups are assigned to TRT counseling. Further, the TRTT will investigate the
efficacy of TRT counseling by comparing Tinnitus Questionnaire scores in the
group of participants assigned to TRT coun- seling and sound therapy achieved with
placebo devices versus Tinnitus Questionnaire scores for those in the group
assigned to standard care, with the assumption that the effect of placebo sound
therapy is negligible. Secondly, the TRTT will assess the efficacy of treatment by
measur- ing the difference between baseline and end-of-treatment Tinnitus
Questionnaire scores in the three treatment groups.
The secondary efficacy outcomes will compare groups by assessing end-of-treatment
and longitudinal changes in scores on the subscales of the Tinnitus Questionnaire; total
and subscales of the Tinnitus Functional Index and Tinnitus Handicap Inventory; TRT
visual analog scale; Digit Symbol Substitution Test; and psychoacoustic mea- sures of
tinnitus pitch and loudness match and loudness discomfort levels. Maintenance of
treatment efficacy will be assessed by comparing scores on the Tinnitus Question- naire,
Tinnitus Functional Index, and Tinnitus Handicap

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Inventory between baseline, the 18-month follow-up visit, and each extended followup visit at 30, 42, and 54 months.
Ethics
The TRTT will be conducted following the ethical prin- ciples of the Declaration of
Helsinki. This study received ethical approval from the institutional review boards of
the University of Alabama for the chairs office and at the Johns Hopkins Bloomberg
School of Public Health for the data coordinating center. Institutional review boards
approving the protocol and informed consent statement at clinical centers include: the
Walter Reed National Military Medical Center institutional review board, the 59th
Medical Wing institutional review board (Wilford Hall Ambulatory Surgical Center
and David Grant Medical Center), clinical investigation depart- ments at Naval
Medical Center San Diego and Naval Hospital Camp Pendleton, and the Naval
Medical Center Portsmouth institutional review board. No study partici- pant will be
enrolled in the study before informed con- sent is obtained and documented by a
signed informed consent statement.
Sample size
We based our sample-size calculation on the difference in Tinnitus Questionnaire
scores between baseline and
18 months of follow-up (end of treatment). We con- sulted experts familiar with the
Tinnitus Questionnaire to estimate the minimal clinically important difference
between study groups. Richard S. Hallam (who devel- oped the Tinnitus
Questionnaire) proposed, An effect size of 0.8 or perhaps 1.0 on the emotional
distress sub- scale is a reasonable criterion for [clinically] significant change,
(personal communication). An effect size of 0.8 to 1.0 on the full Tinnitus
Questionnaire would corres- pond to a change of approximately 10 to 13 points.
Wolfgang Hiller, a researcher with extensive experience with the Tinnitus
Questionnaire stated, A change of less than 5 to 6 points does not mean much,
(personal com- munication). Based on these considerations, we chose to design the
TRTT with sufficient power to detect a ten- point difference for the primary
comparison (that is, between TRT and standard care) and a seven-point dif- ference for
the secondary comparisons (that is, the sep- arate efficacies of sound therapy and TRT
counseling). We assumed a type-I error rate of 0.05, using a two- sided test and 80%
power for the secondary compari- sons. We further assumed that a standard
deviation of
12.5
would hold for all groups and that there would be 10% attrition. Accordingly, by
dividing an of 0.05 among the three comparisons and accounting for 10% attrition,
we estimated that a total of 228 study partici- pants (76 participants in each of the
three groups) will

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be required to yield at least 80% power to detect a seven- point difference for analyses
of the TRT components, sound therapy and TRT counseling [32]. This sample size
provides for greater than 95% power for the primary ana- lysis (TRT versus standard
care). Our sample-size estimate is conservative because the primary outcome is a
longitu- dinal analysis, using data from follow-up visits at 3, 6, 12 and 18 months,
rather than a difference in score between two time points (that is, baseline and end of
treatment at 18 months).
Data management
The TRTT clinical center staff collect study data on paper data collection forms and
enter data online using the TRTT website. All data items are validated against criteria
specified in the data dictionary, including checks for consistency with other responses
and completeness during data entry. Data errors or inconsistencies are flagged and
displayed immediately online during the data entry process. Data flags require
immediate correction or may be set as warnings (missing data). Flags that require
im- mediate correction do not permit submission of the form without correction.
Warnings will not disallow submission of the form, but must be addressed in a timely
manner. Warnings are entered into an error log, and an error re- port is produced by the
system. Any variables that are marked as possibly in error are reported to the clinical
centers. In addition, errors are detected by data coordinat- ing center staff during routine
audits, in which data on copies of paper data collection forms are compared with data
already entered into the database. Sites make correc- tions in the TRTT website
database or verify that the in- formation entered is correct. Any new errors generated
during editing are added to the error log. Immediately fol- lowing completion of entry
of all expected data collection forms for an individual study participant, a set of crossform and cross-visit data queries will be run and the clinic queried for inconsistencies
detected. Official interim data- sets, containing data entered as of a given date, are created for monitoring purposes in conjunction with data and safety monitoring board
interim report generation. These datasets are archived for reference in duplicate
analysis.
Security measures include password protection for each user who is granted
privileges; access is based on need to know. All elements of the database are backed
up daily and weekly onto high-capacity cassette tapes, and monthly backups are
transferred to CD media. In addition to data kept on site, copies of weekly backups are
stored off site in a fireproof safe.
Statistical methods

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Initial analyses will be descriptive in nature, using means, standard deviations, and
proportions to describe
baseline characteristics of the study participants, both
combined and by intervention group. Distributions of continuous variables will be
examined for symmetry, and transforma- tions will be considered for seriously skewed
variables. For continuous variables, one-way analysis of variance will be used to
compare intervention groups on demographic and other baseline characteristics. For
dichotomous or other categorical variables, chi-square tests will be used to compare
intervention groups, and enrolled and excluded groups. Pearson correlation coefficients
will be calculated to assess the strength of the associations among the vari- ous outcome
measures and to examine associations of other covariates with outcome measures;
potential con- founding variables will be considered for inclusion in sec- ondary
analyses involving regression models.
The primary outcome variable will be change in the Tinnitus Questionnaire score,
using spaghetti plots for initial exploratory analyses and longitudinal data ana- lyses
for the primary analytic method. Indicator variables will identify treatment group, with
coefficients in the models representing the primary focus on group differ- ences. Mean
Tinnitus Questionnaire scores will be com- pared between two treatment groups using
generalized estimating equations. The basic model will account for effects of clinical
center, treating audiologist, treatment group, and, possibly, personality traits, as
measured by the State-Trait Anxiety Index or Positive and Negative Affect Schedule.
Other factors that might be included are scores from the Hearing Handicap Inventory
or early completion of treatment. Similar models will be run for the secondary
objectives. These variables in the models will be used to estimate the relation between
various personality characteristics and successful habituation to tinnitus. Interaction
terms between these participant characteristics and treatment groups will be included,
to assess whether the effect of TRT is greater for certain types of participant. Similar
analyses will assess whether age, sex, or other participant characteristics are predictive of successful habituation with or without TRT.
For the secondary efficacy analyses, we will compare Tinnitus Questionnaire mean
scores at 18-months follow- up (end of treatment) among treatment groups using
analysis of covariance, adjusting for baseline Tinnitus Questionnaire scores and
heterogeneity of tinnitus status in the study population. We will also adjust for
important baseline covariates and variables that may be unbalanced at baseline and
potentially related to Tinnitus Questionnaire score. We will also use generalized
estimating equations for this analysis.
We will use this approach with other outcome vari- ables, including the Tinnitus
Questionnaire subscales, global and subscale scores of the Tinnitus Functional Index,
Tinnitus Handicap Inventory, and visual analog scale
of the TRT Interview Form.
We will also compare

baseline audiometric measures, psychoacoustic variables of tinnitus pitch and loudness

match, and loudness dis- comfort levels to evaluate change across time in these
measures.
All analyses will be based on the principle of intention to treat (that is, in the
analysis study participants will be included in the group to which they were
randomized) regardless of whether they adhered to, or completed, the assigned
treatment. For the primary outcome, the only participants who will not be included
will be those for whom Tinnitus Questionnaire could not be assessed at any followup visit due to loss to follow-up. However, we anticipate that few, if any,
participants will be unable to complete at least one follow-up Tinnitus
Questionnaire measure. To account for missing values, we will use multiple
imputation, which assumes that missing data are missing at random.
Organization
Organizational units of the TRTT include a study chairs office, a data coordinating
center, clinical centers, and various committees. The National Institute on Deafness and
Other Communication Disorders (NIDCD) at the National Institutes of Health funds the
TRTT through a cooperative grant arrangement and provides a project officer.
Leadership in the TRTT is shared by the study chair and the director of the data
coordinating center.
The chairs office is responsible for the overall scientific and administrative aspects of
the trial. Study personnel at the chairs office include the study chair, TRT and standard
care training and protocol monitors, a human research protocol monitor, and an
administrative assistant. The chairs office is responsible for supervision of the overall
study by integrating the activities of the data coordinating center and clinical centers,
including recruitment and oversight of the clinical centers. The chairs office provides
assistance to clinical centers on protocol implementation and monitors clinical center
institutional review board ap- proval. It is charged with resolution of all technical and
scientific questions regarding clinical training and treat- ment issues and complications.
The study chair organizes and conducts TRT and standard care training sessions.
Together with the data coordinating center, the study chair implements quality
assurance measures to monitor treatment adherence in TRTT clinical centers. The data
coordinating center oversees scientific aspects of study de- sign, and serves as the focus
of study communications, training, and certification of clinical staff in trial procedures, protocol interpretation, data processing, data ana- lysis, and quality assurance
activities. Staff at the data coordinating center include the director, biostatistician,
director of information management, database program- mer, statistical programmer or
analyst, project coordinator, and research assistants. The data coordinating
center

prepares, maintains, and distributes study documents, data collection forms, and a
web-based data system to process data with computer-based randomization
schedules for each clinical center. The data coordinating center trains clinical center
staff on the study protocol, supervises TRTT data collection and processing, and
performs all study analyses. Quality control and assurance responsi- bilities include
certification of clinical center staff and routine monitoring of recruitment, data
processing, and adherence to study protocol. The data coordinating center is the
official TRTT archive for all study data, and will pre- pare a public use data set of
TRTT data.
Clinical center staff include at least two audiologists, a coordinator, an
otolaryngologist, or study physician, and a data system operator. Clinical centers are
responsible for participant recruitment, treatment administration, and follow-up
according to study protocol. Data man- agement activities at participating clinics
include proper completion of all data collection forms, transmission of that
information to the data coordinating center using the TRTT website accurately and
timely, and responses to requests for data clarification or correction.
The TRTT has three primary standing committees: a steering committee, an
executive committee, and a data and safety monitoring board.
Members of the steering committee include the study chair, data coordinating center
director, biostatistician, clinical center directors, and NIDCD project officer. The
steering committee is responsible for the review and ap- proval of trial procedures,
resolution of technical or op- erational issues, review of study progress and approval
of major changes to the study protocol. The steering committee is also responsible for
acting on advice from the data and safety monitoring board, appointment or
termination of subcommittees, review and approval of ancillary studies, and oversight
of publication of study findings.
The executive committee includes the study chair, data coordinating center director,
and NIDCD project officer, and is responsible for implementation of decisions made
by the steering committee and matters affecting the day- to-day operations of the trial.
The data and safety monitoring board is responsible for ensuring participant safety
and monitoring the over- all performance of the trial. This board reviews the study
data, as they are collected, for evidence of harmful or beneficial treatment effects. The
members of this com- mittee, appointed by the NIDCD, include a chair and three
additional voting members not affiliated with the study. This committee is the only
committee provided with evidence of treatment effects while the study is still in
progress. The data and safety monitoring board usu- ally meets twice a year, but
additional meetings are scheduled as necessary.

Dissemination policy
All TRTT papers that describe the main results of the TRTT (that is, comparisons of
treatment groups) will follow corporate or group authorship format, naming The
Tinnitus Retraining Therapy Trial Research Group as author, with individual
investigators and clinical cen- ter staff acknowledged. No comparison data will be
available prior to completion of the study and no clinic may publish data obtained from
their clinic independ- ently. Writing committees for TRTT papers will include at least
one representative from the chairs office, one from the data coordinating center, and
other study group members based on interest and expertise. All TRTT manuscripts
will be submitted to journals com- plying with the National Institutes of Health Public
Access Policy, and all publications will be archived in PubMed Central, as required by
this policy. Presenta- tions at conferences describing or presenting TRTT re- sults
follow the same guidelines and require clearance by the steering committee.
Public access to protocol and data
The TRTT data will become available to outside inves- tigators at the conclusion of the
trial and following publication of the main study findings. To protect the confidentiality
of participant data, only de-identified data will be made available for secondary
analysis. All second- ary users of data will be asked to sign a data use agree- ment that
stipulates: confidentiality and data security standards must be adhered to by the
recipient; data are
to be used for research purposes approved by the insti- tutional
review board only; no effort will be made to identify individual participants; and data
will not be transferred to other users by the recipient.
Discussion
This report describes a randomized clinical trial that will determine the efficacy of TRT
and its component parts, tinnitus-specific educational counseling and sound ther- apy,
compared with standard care, in a military popula- tion. Two features of the study
highlight efficiency in design. First, we designed the trial with three arms; two arms
differ only by whether placebo or conventional sound generators are used and the third
arm is standard care. This design allows us to make multiple compari- sons and parse
out the separate effects of the TRT com- ponents. In addition, we are conducting the
study in US military hospitals. We chose to conduct the study in this setting given the
higher prevalence of tinnitus among in- dividuals exposed to intense noises. Because
the military population is similar to the general population in all other aspects, we
believe that the study results will be generally applicable.

Because the TRTT is assessing tinnitus-specific health- related quality of life using
three commonly used instru- ments (Tinnitus Questionnaire, Tinnitus Functional Index,
and Tinnitus Handicap Inventory), we will be able to as- sess comparability across
these instruments. We will also assess whether the Digit Symbol Substitution Test is a
useful measure to assess the ability to concentrate in indi- viduals with tinnitus.
A unique feature of the TRTT is the development of a standardized protocol for both
TRT and standard care, as practiced in the military for persons suffering from severe
tinnitus. The TRTT developed a standardized tinnitus- specific educational counseling
component of TRT, com- prised of scripts, a flipchart, and visual aids to be used by all
audiologists at all clinical centers. This standardized treatment protocol allowed
different audiologists across military centers to learn and administer TRT as a treatment for severe tinnitus not only within the trial, but in their clinical practices. In
addition, the TRTT investigators engaged the assistance of General Hearing
Instruments, Inc., in the development of a placebo sound generator, enabling
measurement of the separate effects of the com- ponent parts of the TRT intervention,
tinnitus-specific educational counseling and sound therapy. Both placebo and
conventional sound generators can be used to assess participant compliance by
recording times when the de- vice is worn or not worn. This ability provides for the
monitoring of treatment fidelity. The TRTT investigators also developed a standard
care protocol to achieve uni- formity in the care of tinnitus by surveying clinical
centers before the trial began and incorporating current guideline recommendations
[19]. Standardization of TRT and stand- ard care for use in a multicenter randomized
clinical trial required the essential elements of each intervention to be identified and
standardized across different study audiolo- gists and treatment sites. The subsequent
streamlining and distillation of the essential components meant that all details were
mandated by protocol, but allowed for indi- vidual variation by audiologists within
strict adherence to the essential components. We hope that standardization of the
interventions for the TRTT will facilitate and exped- ite treatment outcomes in the trial
and eventually within the clinical community if either or both TRT and standard care
prove efficacious.
Trial status
The TRTT is currently in the process of recruiting study participants.
Abbreviations
NIDCD: National Institute on Deafness and Other Communication Disorders; TRT: tinnitus retraining
therapy; TRTT: Tinnitus Retraining Therapy Trial.
Competing interests No author has any financial or other competing interest.

Authors contributions
RWS participated in the design and coordination of the study and drafted the manuscript. CF
conceived the study, participated in the design and coordination of the study, and helped to
draft the manuscript. SG developed the standardized TRT protocol for the study. SE developed
the protocol for the standard care for the study. CR developed the biostatistical plan. MC
developed the psychometric aspects of the study design. DS developed the informatics for the
study. MT developed the template protocol for the institutional review board protocol and
consent statements. LMS developed the protocol for staff training and coordination of the study.
GH participated in the design and coordination of the study. GSC, ND, CE, MJ, AH-P, CH, SKR,
BS-I, and MS participated in the design and coordination of the study, assisted in
modifications to the design and methods required in a military medical facility, and
participated in the review and editing phase of the manuscript. All authors critically read and
approved the final manuscript.
Acknowledgements
The TRTT project and the preparation of this manuscript are supported by the NIDCD: awards
U01DC007411 to CF, TRTT study chair, and U01DC007422 to RS, director of the data
coordinating center. The sponsor had no role in the design, data collection, analysis, or writing
of the manuscript or decision to submit the manuscript for publication.
The views expressed in this article are those of the authors and do not necessarily reflect the
official policy or position of the Departments of the Navy and Air Force, Department of
Defense, or the United States Government. This work was prepared as part of official duties
performed by military service members and civilian employees participating in the TRTT
project. Title 17 USC. 105 provides that Copyright protection under this title is not available for
any work of the United States Government. Title 17 USC. 101 defines a United States
Government work as a work prepared by a military service member or employee of the United
States Government as part of that persons official duties.