Tinnitus Retraining Therapy Trial

Study Overview
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Brief Summary
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The primary purpose of the Tinnitus Retraining Therapy Trial (TRTT) is to assess the efficacy of tinnitus retraining therapy (TRT) as a treatment for severe debilitating tinnitus. TRT is a non-medical intervention that uses directive counseling (DC) and sound therapy (ST)to habituate the patient's associated negative emotional reactions to tinnitus, its perception, and ultimately, its impact on the patient's life.

Detailed Description
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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.

Official Title
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Tinnitus Retraining Therapy Trial

Conditions
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Subjective Tinnitus

Intervention / Treatment
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* Device: Conventional sound generator (SG)
* Device: Placebo sound generator (placebo SG)
* Behavioral: Standard of Care (SC)
* Behavioral: Directive Counseling (DC)
* Behavioral: Directive Counseling (DC)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TRT<br>TRT includes treatment with a conventional sound generator (SG) and directive counseling (DC) | Device: Conventional sound generator (SG)<br>* Conventional SGs: Tranquil model sound generators (General Hearing Instruments, Inc.) are either inside or outside-the-ear devices that generate low-level noise, which is set at or just below the patient's mixing point (i.e., the noise level that just blends with the study participant's tinnitus)<br>Behavioral: Directive Counseling (DC)<br>* Directive Counseling (DC): two-hour educational session during which the patient is given information regarding the nature of the tinnitus problem and related problems such as hearing loss and sound intolerance; visual aids to review the audiological/tinnitus/ hyperacusis evaluation, provide instruction on anatomy and physiology of hearing and tinnitus, introduce the Jastreboff neurophysiological model of tinnitus and related concepts of habituation, and describe and recommend the use of ST and environmental sound in the habituation process.<br>|
| Other: Partial TRT<br>Partial TRT includes treatment with a placebo sound generator (placebo SG) and directive counseling (DC). | Device: Placebo sound generator (placebo SG)<br>* Tranquil model placebo sound generators (General Hearing Instruments, Inc.) are either inside or outside-the-ear devices that generate a sound different from the active devices.<br>Behavioral: Directive Counseling (DC)<br>* Directive Counseling (DC): two-hour educational session during which the patient is given information regarding the nature of the tinnitus problem and related problems such as hearing loss and sound intolerance; visual aids to review the audiological/tinnitus/ hyperacusis evaluation, provide instruction on anatomy and physiology of hearing and tinnitus, introduce the Jastreboff neurophysiological model of tinnitus and related concepts of habituation, and describe and recommend the use of ST and environmental sound in the habituation process.<br>|
| Other: Standard of Care (SC)<br>The standard of care arm includes care as typically delivered in US military medical centers | Behavioral: Standard of Care (SC)<br>* The standard of care treatment will be similar to that typically provided to patients with severe tinnitus at participating military medical centers and as described in the American Speech-Language-Hearing Association (ASHA) Preferred Practice Patterns in Audiology (ASHA, 2006). Tinnitus management will be based on the patient's complaints, history, audiologic evaluation, and self-assessment. The goal of the tinnitus management is to reduce negative cognitive, affective, physical, and behavioral reactions to tinnitus and to improve the patient's well-being and quality of life. Specific treatment recommendations will be individualized to reflect the participant's concerns and abilities, as well as his or her engagement in the decision-making process regarding treatment options.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Tinnitus Questionnaire (TQ) From Baseline to 3, 6, 12, and 18 Months | The TQ is a tinnitus-specific health-related quality of life instrument with 52 statements that the respondent marks as true, partly true, or not true. The TQ is scored from 0 to 102, with higher scores indicating more of an impact of the tinnitus on quality of life. Subscales include emotional distress, intrusiveness, auditory perceptual difficulties, sleep disturbance,and somatic complaints. | Baseline to 3, 6, 12, and 18 months follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Tinnitus Functional Index (TFI) From Baseline to 3, 6, 12, and 18 Months | The TFI is a tinnitus-specific health -related quality of life instrument. Subscales include intrusiveness, reduced sense of control, cognitive interference, sleep disturbance, auditory difficulties (related to tinnitus), relaxation interference, reduced quality of life, and emotional distress. The total and each subscale score ranges from 0 to 100 with higher scores indicated a greater impact of tinnitus on quality of life. | Baseline and 3, 6, 12, and 18 months | 
| Change in Tinnitus Handicap Inventory (THI) Score From Baseline to 3, 6, 12, and 18 Months Follow-up | Change in THI score from baseline to 3 months follow-up. The THI is a tinnitus-specific health-related quality of life instrument. Subscales include the functional (scored 0 to 44), emotional (scored 0 to 36) and catastrophic (scored 0 to 20). The total score ranges from 0 to 100 with higher scores indicating a greater impact of tinnitus on quality of life. | Baseline and 3. 6. 12. and 18 months | 
| Change in Tinnitus Retraining Therapy Interview Visual Analogue Scales at 3, 6, 12, and 18 Months Follow-up | 10 point visual analog scale asking How much of a problem is tinnitus? on a scale from 0 no problem at all to 10 as much as you can imagine | Baseline to 6, 12, and 18 months follow-up | 
| Change in Tinnitus Questionnaire Emotional Distress Sub-scale Scores From Baseline to 3, 6, 12, and 18 Months. | Change in Tinnitus Questionnaire emotional distress sub-scale from baseline to follow-up. Sub-scale scores range from 0 to 38 with higher scores representing greater emotional distress. | Baseline to 3, 6, 12, and 18 months follow-up | 
| Change in Tinnitus Questionnaire Intrusiveness Sub-scale Scores. | Change in Tinnitus Questionnaire intrusiveness sub-scale from baseline to follow-up. Sub-scale scores range from 0 to 14 with higher scores representing greater intrusiveness of the tinnitus. | Baseline to 3, 6, 12, and 18 months follow-up | 
| Change in Tinnitus Questionnaire Auditory Perceptual Difficulties Sub-scale Scores. | Change in Tinnitus Questionnaire auditory perceptual sub-scale from baseline to follow-up. Sub-scale scores range from 0 to 14 with higher scores representing greater auditory difficulties. | Baseline to 3, 6, 12, and 18 months follow-up | 
| Change in Tinnitus Questionnaire Sleep Disturbance Sub-scale Scores. | Change in Tinnitus Questionnaire sleep disturbance sub-scale from baseline to follow-up. Sub-scale scores range from 0 to 8 with higher scores representing greater sleep disturbance. | Baseline to 3, 6, 12, and 18 months follow-up | 
| Change in Tinnitus Questionnaire Somatic Complaint Sub-scale Scores. | Change in Tinnitus Questionnaire somatic complaint sub-scale from baseline to follow-up. Sub-scale scores range from 0 to 8 with higher scores representing greater somatic complaints. | Baseline to 3, 6, 12, and 18 months follow-up | 
| Change in Tinnitus Functional Index Intrusiveness Sub-scale Scores. | Change in Tinnitus Functional Index intrusiveness sub-scale from baseline to follow-up. Sub-scale scores range from 0 to 100 with higher scores representing greater intrusiveness of the tinnitus. | Baseline to 3, 6, 12, and 18 months follow-up | 
| Change in Tinnitus Functional Index Reduced Sense of Control Sub-scale Scores. | Change in Tinnitus Functional Index reduced sense of control sub-scale from baseline to follow-up. Sub-scale scores range from 0 to 100 with higher scores representing greater reduction of control. | Baseline to 3, 6, 12, and 18 months follow-up | 
| Change in Tinnitus Functional Index Cognitive Interference Sub-scale Scores. | Change in Tinnitus Functional Index cognitive interference sub-scale from baseline to follow-up. Sub-scale scores range from 0 to 100 with higher scores representing greater cognitive interference. | Baseline to 3, 6, 12, and 18 months follow-up | 
| Change in Tinnitus Functional Index Sleep Disturbance Sub-scale Scores. | Change in Tinnitus Functional Index sleep disturbance sub-scale from baseline to follow-up. Sub-scale scores range from 0 to 100 with higher scores representing greater sleep disturbance. | Baseline to 3, 6, 12, and 18 months follow-up | 
| Change in Tinnitus Functional Index Auditory Difficulties Sub-scale Scores. | Change in Tinnitus Functional Index auditory difficulties sub-scale from baseline to follow-up. Sub-scale scores range from 0 to 100 with higher scores representing greater auditory difficulties. | Baseline to 3, 6, 12, and 18 months follow-up | 
| Change in Tinnitus Functional Index Relaxation Interference Sub-scale Scores. | Change in Tinnitus Functional Index relaxation interference sub-scale from baseline to follow-up. Sub-scale scores range from 0 to 100 with higher scores representing greater relaxation interference. | Baseline to 3, 6, 12, and 18 months follow-up | 
| Change in Tinnitus Functional Index Emotional Distress Sub-scale Scores. | Change in Tinnitus Functional Index emotional distress sub-scale from baseline to follow-up. Sub-scale scores range from 0 to 100 with higher scores representing greater emotional distress. | Baseline to 3, 6, 12, and 18 months follow-up | 
| Change in Tinnitus Functional Index Reduced Quality of Life Sub-scale Scores. | Change in Tinnitus Functional Index reduced quality of life sub-scale from baseline to follow-up. Sub-scale scores range from 0 to 100 with higher scores representing greater reduction in quality of life. | Baseline to 3, 6, 12, and 18 months follow-up | 
| Change in Tinnitus Handicap Inventory Functional Sub-scale Scores. | Change in Tinnitus Handicap Inventory functional sub-scale from baseline to follow-up. Sub-scale scores range from 0 to 44 with higher scores representing greater functional difficulties. | Baseline to 3, 6, 12, and 18 months follow-up | 
| Change in Tinnitus Handicap Inventory Emotional Sub-scale Scores. | Change in Tinnitus Handicap Inventory emotional sub-scale from baseline to follow-up. Sub-scale scores range from 0 to 36 with higher scores representing greater emotional distress. | Baseline to 3, 6, 12, and 18 months follow-up | 
| Change in Tinnitus Handicap Inventory Catastrophic Sub-scale Scores. | Change in Tinnitus Handicap Inventory catastrophic sub-scale from baseline to follow-up. Sub-scale scores range from 0 to 20 with higher scores representing greater catastrophic effect of the tinnitus. | Baseline to 3, 6, 12, and 18 months follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tinnitus, tinnitus retraining therapy, standard of care, directive counseling, sound therapy, tinnitus questionnaire, tinnitus handicap inventory