Clinical trial NCT01177137: Tinnitus Retraining Therapy Trial
Official title: Tinnitus Retraining Therapy Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Subjective Tinnitus
Keywords: tinnitus
tinnitus retraining therapy
standard of care
directive counseling
sound therapy
tinnitus questionnaire
tinnitus handicap inventory
Lead sponsor: Johns Hopkins Bloomberg School of Public Health
Sponsor class: OTHER
Collaborators: name: National Institute on Deafness and Other Communication Disorders (NIDCD)
name: University of Alabama, Tuscaloosa
name: David Grant U.S. Air Force Medical Center
name: 59th Medical Wing
name: United States Naval Medical Center, San Diego
name: United States Naval Medical Center, Portsmouth
name: Naval Hospital Camp Pendleton
name: Walter Reed National Military Medical Center
First posted: 2010-08-06
Enrollment: 151
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Tinnitus Questionnaire (TQ) From Baseline to 3, 6, 12, and 18 Months
timeFrame: Baseline to 3, 6, 12, and 18 months follow-up
Secondary outcomes:
measure: Change in Tinnitus Functional Index (TFI) From Baseline to 3, 6, 12, and 18 Months
timeFrame: Baseline and 3, 6, 12, and 18 months
measure: Change in Tinnitus Handicap Inventory (THI) Score From Baseline to 3, 6, 12, and 18 Months Follow-up
timeFrame: Baseline and 3. 6. 12. and 18 months
measure: Change in Tinnitus Retraining Therapy Interview Visual Analogue Scales at 3, 6, 12, and 18 Months Follow-up
timeFrame: Baseline to 6, 12, and 18 months follow-up
measure: Change in Tinnitus Questionnaire Emotional Distress Sub-scale Scores From Baseline to 3, 6, 12, and 18 Months.
timeFrame: Baseline to 3, 6, 12, and 18 months follow-up
measure: Change in Tinnitus Questionnaire Intrusiveness Sub-scale Scores.
timeFrame: Baseline to 3, 6, 12, and 18 months follow-up
measure: Change in Tinnitus Questionnaire Auditory Perceptual Difficulties Sub-scale Scores.
timeFrame: Baseline to 3, 6, 12, and 18 months follow-up
measure: Change in Tinnitus Questionnaire Sleep Disturbance Sub-scale Scores.
timeFrame: Baseline to 3, 6, 12, and 18 months follow-up
measure: Change in Tinnitus Questionnaire Somatic Complaint Sub-scale Scores.
timeFrame: Baseline to 3, 6, 12, and 18 months follow-up
measure: Change in Tinnitus Functional Index Intrusiveness Sub-scale Scores.
timeFrame: Baseline to 3, 6, 12, and 18 months follow-up
measure: Change in Tinnitus Functional Index Reduced Sense of Control Sub-scale Scores.
timeFrame: Baseline to 3, 6, 12, and 18 months follow-up
measure: Change in Tinnitus Functional Index Cognitive Interference Sub-scale Scores.
timeFrame: Baseline to 3, 6, 12, and 18 months follow-up
measure: Change in Tinnitus Functional Index Sleep Disturbance Sub-scale Scores.
timeFrame: Baseline to 3, 6, 12, and 18 months follow-up
measure: Change in Tinnitus Functional Index Auditory Difficulties Sub-scale Scores.
timeFrame: Baseline to 3, 6, 12, and 18 months follow-up
measure: Change in Tinnitus Functional Index Relaxation Interference Sub-scale Scores.
timeFrame: Baseline to 3, 6, 12, and 18 months follow-up
measure: Change in Tinnitus Functional Index Emotional Distress Sub-scale Scores.
timeFrame: Baseline to 3, 6, 12, and 18 months follow-up
measure: Change in Tinnitus Functional Index Reduced Quality of Life Sub-scale Scores.
timeFrame: Baseline to 3, 6, 12, and 18 months follow-up
measure: Change in Tinnitus Handicap Inventory Functional Sub-scale Scores.
timeFrame: Baseline to 3, 6, 12, and 18 months follow-up
measure: Change in Tinnitus Handicap Inventory Emotional Sub-scale Scores.
timeFrame: Baseline to 3, 6, 12, and 18 months follow-up
measure: Change in Tinnitus Handicap Inventory Catastrophic Sub-scale Scores.
timeFrame: Baseline to 3, 6, 12, and 18 months follow-up
Other outcomes:
Locations:
city: Camp Pendleton
country: United States
facility: Naval Hospital Camp Pendleton
state: California
city: San Diego
country: United States
facility: Naval Medical Center
state: California
city: Travis Air Force Base
country: United States
facility: David Grant Medical Center
state: California
city: Bethesda
country: United States
facility: Walter Reed National Military Medical Center
state: Maryland
city: Lackland Air Force Base
country: United States
facility: Wilford Hall Medical Center
state: Texas
city: Portsmouth
country: United States
facility: Portsmouth Naval Medical Center
state: Virginia
Study officials:
affiliation: The University of Alabama, Tuscaloosa
name: C. Craig Formby, PhD
role: STUDY_CHAIR
affiliation: Johns Hopkins Bloomberg School of Public Health
name: Roberta W Scherer, PhD
role: STUDY_DIRECTOR
References:
citation: Scherer RW, Formby C, Gold S, Erdman S, Rodhe C, Carlson M, Shade D, Tucker M, Sensinger LM, Hughes G, Conley GS, Downey N, Eades C, Jylkka M, Haber-Perez A, Harper C, Russell SK, Sierra-Irizarry B, Sullivan M; Tinnitus Retraining Therapy Trial Research Group. The Tinnitus Retraining Therapy Trial (TRTT): study protocol for a randomized controlled trial. Trials. 2014 Oct 15;15:396. doi: 10.1186/1745-6215-15-396.
citation: Formby C, Scherer R; TRTT Study Group. Rationale for the tinnitus retraining therapy trial. Noise Health. 2013 Mar-Apr;15(63):134-42. doi: 10.4103/1463-1741.110299.
citation: Formby C, Yang X, Scherer RW. Contributions of Counseling and Sound Generator Use in Tinnitus Retraining Therapy: Treatment Response Dynamics Assessed in a Secondary Analysis of a Randomized Trial. J Speech Lang Hear Res. 2022 Feb 9;65(2):816-828. doi: 10.1044/2021_JSLHR-21-00210. Epub 2022 Jan 24.
citation: Scherer RW, Erdman SA, Gold S, Formby C; TRTT Research Group. Treatment fidelity in the Tinnitus Retraining Therapy Trial. Trials. 2020 Jul 23;21(1):670. doi: 10.1186/s13063-020-04530-9.
citation: Tinnitus Retraining Therapy Trial Research Group; Scherer RW, Formby C. Effect of Tinnitus Retraining Therapy vs Standard of Care on Tinnitus-Related Quality of Life: A Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2019 Jul 1;145(7):597-608. doi: 10.1001/jamaoto.2019.0821.
citation: Scherer RW, Sensinger LD, Sierra-Irizarry B, Formby C; TRTT Research Group. Lessons learned conducting a multi-center trial with a military population: The Tinnitus Retraining Therapy Trial. Clin Trials. 2018 Oct;15(5):429-435. doi: 10.1177/1740774518777709. Epub 2018 May 23.