Clinical Trial of Sound-Based Versus Behavioral Therapy for Tinnitus
Phase: NA
Conditions: Tinnitus
Sponsor: VA National Center for Rehabilitative Auditory Research

 
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COVER PAGE 
 
 
Official Title 
Clinical Trial of Sound-Based Versus Behavioral Therapy for Tinnitus 
 
 
NCT number 
NCT03022084 
 
 
Document Date 
Last IRB approval date 13 MAR 2018 

 
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Research Protocol 
 
 
Title: Clinical Trial of Sound-Based versus Behavioral Therapy for Tinnitus 
 
Investigators  
PI: James A. Henry, Ph.D.  
Co-PI: Sarah Theodoroff, Ph.D. 
 
Specific Aims 
The purpose of this study is to determine if a customized therapy, Acoustic Coordinated 
Reset (CR) Neuromodulation (also referred to as Desyncra) reduces tinnitus-related 
distress with comparable efficacy as for Cognitive Behavioral Therapy (CBT) for people 
who have bothersome tinnitus. 
 
Inclusion Criteria 
 Age ≥18 years  
 Primary and persistent tinnitus [defined by AAO-HNSF guidelines (Tunkel et al, 
2014); 6 months or longer in duration] 
 Tonal tinnitus  
 Dominant tinnitus frequency measured between 0.2 and 10 kHz 
 Tinnitus Questionnaire (TQ) score ≥30 at screening (to confirm moderate to 
severe tinnitus) 
 No current participation in other tinnitus therapy program 
 Willing and able to listen to the acoustic prescription for 4-6 hours daily during the 
trial 
 Able to pass the Tone Audibility Assessment with factor of 1.1   
 
Exclusion Criteria 
 Secondary/somatic tinnitus due to a suspected underlying disease (defined by 
AAO-HNSF guidelines) 
 Atonal, pulsatile, intermittent, or occasional tinnitus (determined by self-report 
and by the Tinnitus Screener) 
 Any hearing threshold >70 dB HL from .25-8 kHz, unless subject passes the 
Tone Audibility Assessment screening with a factor of 1.1 
 Any health or other problems that may prevent the person from completing the 
study procedures as determined by investigator 
 Participant reports current (within the past week) suicidal ideation and/or 
homicidal ideation 
 Use of medication that may trigger tinnitus [e.g., quinine derivatives, 
aminoglycoside antibiotics, daily high dose non-steroidal anti-inflammatory drugs 
≥1000 mg, salicylates (when not prescribed as a low dose for cardiac health), 
loop diuretics and chemotherapy agents like cis-platin] at the discretion of the 
Principal Investigator 
 Conductive hearing loss defined as an air-bone gap of 15 dB or greater at more 

 
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than two frequencies in one ear 
 Visible congenital or traumatic deformity of the ear 
 History of active drainage from the ear within the past 90 days 
 History of sudden or rapidly progressive hearing loss within the past 90 days 
 Inability to read and respond appropriately to instructions that appear on the 
computer screen, and/or to perform all of the study procedures 
 
Desyncra Group. Subjects randomized to the Desyncra group will be fit with the 
devices. The Research Audiologists will be trained by a Desyncra representative to 
dispense the Desyncra for Tinnitus Therapy System according to company guidelines. 
The devices are fitted and programmed based on the subject’s tinnitus characteristics 
and hearing ability at the first visit and the subject will use the device for 4-6 hours per 
day for 24 weeks.  
 
In the case of a subject reporting his/her tinnitus has completely vanished, the subject 
will be instructed to reduce the amount of time using the therapy device to 1 hour per 
day. In the event that the tinnitus perception comes back, the subject would increase 
the amount of time using the device back to 4-6 hours per day. 
 
If a subject’s tinnitus characteristics become outside the range where tinnitus is 
treatable (e.g., too-high or too-low tinnitus pitch), the clinician may stop therapy for up to 
2 weeks. Any changes in the therapy schedule will be documented accordingly.  
 
CBT Group. Subjects randomized to this group will receive CBT consistent with best 
practice guidelines. Subjects will attend 6 CBT therapy sessions over the course of 8 
weeks following baseline performed by a psychotherapist as per the recommendations 
outlined in the AAO-HNSF guideline (Tunkel et al 2014).  
 
Step-by-Step Guidance on Conducting the Study 
Recruitment 
 Post ads at the VA Portland Health Care System (VAPORHCS; e.g., audiology, 
primary care, women’s health clinics) and in the surrounding community 
 Place ads in newspaper (paper and/or online); post online advertising; contact 
previous participants who consented to contribute their information into data 
repositories  
 Mail recruitment letters to heath care clinics and facilities in Oregon and 
Washington (USA) 
 
Telephone Screening 
 Screen candidates over the phone using screening script; if eligible, gather 
information from candidate and schedule initial appointment 
 
Visit 1: In-Person Screening/Baseline  
 Administer informed consent 

 
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 HIPAA authorization 
 Administer questionnaires 
 Study staff may opt to use the Sound Finder with candidates (classifies tinnitus 
as tonal vs. noisy perception) 
 Audiologic testing 
 Tinnitus pitch matching procedure using procedure specified by Desyncra Inc. 
 
Visit 2 (1 week after screening completed, approximately ±1 week) 
 All subjects will complete the pitch matching procedure and questionnaires  
 Subjects in the Desyncra group will have their device adjusted according to 
manufacturer guidelines 
 Subjects in the CBT group will complete their 1st CBT session 
 Subjects are paid $40 for attending the visit 
 
Follow-up to Visit 2 for subjects randomized to the Desyncra arm 
 An audiologist will call subjects randomized to the Desyncra arm approximately 1 
to 2 weeks after Visit 2 to follow-up and see how the subject is doing with the 
sound-based therapy 
 
Visit 3 (4 weeks after screening completed, approximately ±1 week) 
 All subjects will complete the questionnaires  
 Subjects in the Desyncra group will complete the pitch matching procedure and 
have their device adjusted according to manufacturer guidelines 
 Subjects in the CBT group will complete their 4th CBT session 
 Subjects are paid $40 for attending the visit  
 
Visit 4 (8 weeks after screening completed, approximately ±2 weeks) 
 All subjects will complete the pitch matching procedure and questionnaires 
 Subjects in the Desyncra group will have their device adjusted according to 
manufacturer guidelines 
 Subjects in the CBT group will complete their 6th and final CBT session 
 Subjects are paid $40 for attending the visit 
 
Visit 5 (16 weeks after screening completed, approximately ±2 weeks) 
 All subjects will complete the questionnaires 
 Subjects in the Desyncra group will complete the pitch matching procedure and 
have their device adjusted according to manufacturer guidelines 
 Subjects are paid $40 for attending the visit 
 
Visit 6 (24 weeks after screening completed, approximately ±2 weeks) 
 All subjects will complete the pitch matching procedure and questionnaires 
 All subjects will complete an exit interview 
 Subjects in the Desyncra group will discontinue use of the device 
 Subjects are paid $40 for attending the visit 

 
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Visit 7 (28 weeks after screening completed, approximately ±2 weeks) 
 All subjects will complete the pitch matching procedure and questionnaires 
 Subjects are paid $40 for attending this final visit 
 Desyncra group will have the opportunity to keep their devices 
 CBT group will have the opportunity to be fit with and receive the Desyncra 
device  
 Any participant who keeps the Desyncra device will be given information on how 
to receive assistance from a local provider or company representative for device-
related concerns 
 
Statistical Analysis Plan 
A Bayesian approach to the analysis of outcome data will be used. Based on 
simulations across several conditions, we anticipate requiring a total of no more than 
200 subjects to have at least 80% power to identify a significant benefit of Desyncra 
therapy compared to CBT. 
 
Data from this study will be provided to the NCRAR Data Manager who will develop and 
maintain a database with all study data. Either the Data Manager or other study 
personnel (e.g. Research Assistant) will enter the data. The Data Manager will perform 
double entry of the data and check for any errors, which will be remediated. After the 
study is complete and all data are entered and verified, the Data Manager will conduct 
preliminary analyses of the data to determine if there are any differences in outcomes 
between groups. These analyses will be overseen by the NCRAR Biostatistician who 
will conduct further analyses as necessary.  
 
A preliminary analysis will be conducted after a total of ~30 subjects have been 
randomized and completed the 16 week follow-up visit. The first formal interim analysis 
will be conducted after a total of ~30 subjects have been randomized and completed the 
24 week follow-up visit or ~16 subjects per treatment arm. A second formal interim 
analysis will occur after a total of ~72 subjects have been randomized (~31 subjects per 
treatment arm) and completed the 24-week follow-up. The primary endpoint of this 
study occurs 24 weeks after being dispensed the Desyncra device at which time the 
primary outcome measure, the TQ, is repeated.  
 
The efficacy of Desyncra will be assessed by contrasting the Desyncra and CBT 
subjects’ change from baseline on the TQ outcome. The δ parameters describe the 
overall change from baseline common to both treatment arms. The φ parameters 
describe the benefits of Desyncra over CBT in this study. We assume that the TQ 
observations are Gaussian random variables with population mean defined above plus 
a subject-specific random intercept θi, and with residual standard deviation σ.