Tinnitus Retraining Therapy Trial

The Tinnitus Retraining Therapy Trial (TRTT), funded by the National Institute of Deafness
and Other Communication Disorders, is a multi-center randomized clinical trial testing the
efficacy of tinnitus retraining therapy (TRT) versus standard-of-care (SC) treatment in
individuals who have self-perceived intolerable tinnitus. TRT is a non-medical intervention
that uses directive counseling (DC) and low-level sound therapy (ST) achieved through sound
generators (SGs) to habituate the patient's associated negative emotional reactions
(annoyance) to tinnitus, its perception (awareness) and, ultimately, its impact on the
participant's life. Study participants will include active and retired military personnel of
the U. S. Armed Forces and their dependents who suffer from severe tinnitus. The study will
be conducted at flagship Air Force, and Navy Medical Centers.

This trial will evaluate the efficacy of TRT and its components (DC and ST) versus the
standard of care (SC) as administered in the military by comparing the efficacy of:

- (1) TRT (DC and ST achieved using conventional sound generators) versus SC;

- (2) TRT versus partial TRT (DC and placebo sound generators) to evaluate the separate
effect of sound therapy, under the assumption that placebo noise generator will not
provide any meaningful sound therapy beyond that found in SC;

- (3) partial TRT versus SC to evaluate the separate effect of DC.

Eligibility will be determined at the Baseline Eligibility Visit, which will consist of a
medical and tinnitus history, physical examination, and baseline
audiological/tinnitus/hyperacusis evaluation. Study participants will also complete a series
of quality of life and psychological profile tests. Study Audiologists will administer the
randomly assigned treatment. Follow-up visits at Clinical Centers will take place at 3, 6,
12, and 18 months and include completion of tinnitus outcome questionnaires at all visits.
Psychometric testing and audiological/tinnitus/hyperacusis evaluation will take place at the
6, 12, and 18 month visits. Evaluation of audiometric pure tone and loudness discomfort level
also will take place at treatment visits.

The primary outcome to be measured in the TRTT will be change in scores on the Tinnitus
Questionnaire (TQ) longitudinally assessed between baseline and follow-up (i.e., at 3, 6, 12
and 18 months following treatment). Secondary outcomes include changes in the sub-scales of
the TQ, change in scores from the Tinnitus Handicap Inventory (THI), Tinnitus Functional
Index (TFI), Hearing Handicap Inventory (HHI), and TRT visual analogue scales, and change in
the Digit Symbol Substitution Test (DSST). Psychometric secondary outcomes also include
change in psychoacoustic variables related to the tinnitus sensation, including tinnitus
pitch and loudness match, and loudness discomfort level.

The TRTT is designed to have sufficient power to detect a minimal clinically important
difference in the Tinnitus Questionnaire (TQ) i.e., a 10 point difference between TRT and SC
groups on change in TQ global scores longitudinally assessed over the course of follow-up and
a 7-point difference on TQ score by TRT components, DC and ST.

Inclusion Criteria:

- Age 18 years or above

- Subjective severe tinnitus, defined as a score on the Tinnitus Questionnaire (TQ)
greater than or equal to 40

- Eligible for care at a Department of Defense Clinical Center

- Speaks English well enough to complete a series of questionnaires and benefit from
counseling

Exclusion Criteria:

- Involvement in pending tinnitus-related financial claims or litigation except that
associated with usual Veterans' Administration retirement claims

- Tinnitus of less than 12 months duration

- Treatment for tinnitus within previous 12 months

- Routine unavoidable exposure to hazardous noise

- Use of a cancer chemotherapeutic drug within previous 12 months

- Treatment for head or neck injury within previous 24 months

- Treatment for an emotional, psychological, or psychiatric condition within previous 12
months resulting in inability to participate in the trial or complete all followup
visits, as assessed by best clinical judgment

- Requirement for use of an ototoxic drug

- Hearing impairment, defined by audiometric thresholds > 30 dB HL at and below 2,000 Hz
and > 40 dB HL at 4,000 and 8,000 Hz

- Required use of hearing aids

- Fluctuating hearing loss at a level that would interfere with the reliability of study
results

- One or more prominent spontaneous otoacoustic emissions, defined as the presence of a
spontaneous otoacoustic emission spike that is 3 or more times larger than the
measured variation in amplitude across the remaining frequency range and/or if the
emission corresponds in pitch to the tinnitus pitch

- Pulsatile somatosounds suggesting presence of abnormal vasculature or high blood
pressure contributing to the tinnitus

- Feigning tinnitus or hearing loss

- Evidence by audiological testing of a treatable etiology of the tinnitus, such as
conductive hearing impairment as shown by pure-tone thresholds, abnormal acoustic
immittance, abnormal stapedial reflex test, or abnormal auditory brainstem response

- Predisposing disease with tinnitus symptoms amenable to medical or surgical
intervention, including but not limited to; chronic otitis media, otosclerosis,
vestibular disorder or dizziness, Eustachian tube, middle ear, or inner ear disease,
Lyme disease or ear autoimmune disease, malocclusion or temporomandibular joint
disease, uncontrolled allergies, aberrant ear, head, or neck blood vasculature or
glomus tumor, neurological condition such as multiple sclerosis or ear-related
demyelinating disease, perilymphatic fistula, or facial weakness or paralysis

- Meniere's disease

- Uncontrolled diabetes, defined as blood glucose consistently ≥ 200 mg/dl or an HBA1c
above 8%

- Evidence from any laboratory study that suggests an etiology for the tinnitus that is
treatable, including, but not limited to, abnormal thyroid stimulating hormone (TSH)
or thyroid hormone (T3 or T4) levels, positive fluorescent treponemal antibody (FTA)
test, or positive Lyme titer

- Evidence of a tumor contributing to the tinnitus, including an acoustic neuroma (or
vestibular schwannoma), cerebellopontine angle tumor, skull base tumor, or any other
type of tumor that the examining physician believes is responsible for the tinnitus

- Diagnosis of traumatic head or brain injury requiring treatment

- Diagnosis of an emotional, psychological, or psychiatric condition requiring treatment
and resulting in inability to participate in the trial or complete all followup
visits, as assessed by best clinical judgment

- Inability or unwillingness of patient to comply with study requirements

- Unwillingness of Clinical Center Director to randomize the patient to treatment due to
the presence of any condition, physical, mental or social, which is likely to affect
the patient returning for follow-up visits on schedule or which is likely to impair
his or her performance on the functional tests

- Inability or unwillingness of patient to provide informed consent