Bi-modal stimulation in the treatment of tinnitus: a study protocol for an exploratory trial to optimise stimulation parameters and patient subtyping

Abstract

IntroductionTinnitus is the perception of sound in the absence of a corresponding external acoustic stimulus. Bimodal neuromodulation is emerging as a promising treatment for this condition. The main objectives of this study are to investigate the relevance of interstimulus timing and the choices of acoustic and tongue stimuli for a proprietary bimodal (auditory and somatosensory) neuromodulation device, as well as to explore whether specific subtypes of patients are differentially responsive to this novel intervention for reducing the symptoms of chronic tinnitus.Methods and analysisThis is a two-site, randomised, triple-blind, exploratory study of a proprietary neuromodulation device with a pre–post and 12-month follow-up design. Three different bimodal stimulation parameter sets will be examined. The study will enrol 342 patients, split 80:20 between two sites (Dublin, Ireland and Regensburg, Germany), to complete 12 weeks of treatment with the device. Patients will be allocated to one of three arms using a stepwise stratification according to four binary categories: tinnitus tonality, sound level tolerance (using loudness discomfort level of <60 dB SL as an indicator for hyperacusis), hearing thresholds and presence of a noise-induced audiometric profile. The main indicators of relative clinical efficacy for the three different parameter sets are two patient-reported outcomes measures, the Tinnitus Handicap Inventory and the Tinnitus Functional Index, after 12 weeks of intervention. Clinical efficacy will be further explored in a series of patient subtypes, split by the stratification variables and by presence of a somatic tinnitus. Evidence for sustained effects on the psychological and functional impact of tinnitus will be followed up for 12 months. Safety data will be collected and reported. A number of feasibility measures to inform future trial design include: reasons for exclusion, completeness of data collection, attrition rates, patient’s adherence to the device usage as per manufacturer’s instructions and evaluation of alternative methods for estimating tinnitus impact and tinnitus loudness.Ethics and disseminationThis study protocol is approved by the Tallaght Hospital/St. James’s Hospital Joint Research Ethics Committee in Dublin, Ireland, and by the Ethics Committee of the University Clinic Regensburg, Germany. Findings will be disseminated to relevant research, clinical, health service and patient communities through publications in peer-reviewed and popular science journals and presentations at scientific and clinical conferences.Trial registration numberThe trial is registered on ClinicalTrials.gov (NCT02669069) Pre-results.

Non-Invasive Neuromodulation for Tinnitus

“…In another approach, sounds are simultaneously applied with electrical stimulation of the tongue [41,42]. This approach is based on the idea that tinnitus is caused by auditory deafferentation and bimodal stimulation may compensate for the auditory deafferentation by stimulating the somatosensory system.…”

“…This approach is based on the idea that tinnitus is caused by auditory deafferentation and bimodal stimulation may compensate for the auditory deafferentation by stimulating the somatosensory system. The combined application of sounds and electrical stimulation to the tongue was investigated in two large trials (involving more than 500 patients) and the results have not been published yet [41,42].…”

Bimodal neuromodulation combining sound and tongue stimulation reduces tinnitus symptoms in a large randomized clinical study

“…On the basis of the positive efficacy and safety outcomes in a previous human pilot study presenting sound and tongue stimulation to treat tinnitus (31), along with supporting animal data (17), we pursued a double-blind randomized clinical study (ClinicalTrials. gov, NCT02669069) (41) to further evaluate different parameter settings of bimodal neuromodulation in a broad tinnitus population. Bimodal stimulation was delivered using a medical device (referred to as MBT in the study; marketed as Lenire) that pairs sound with electrical stimulation of the tongue (Fig.…”

Noninvasive Bimodal Neuromodulation for the Treatment of Tinnitus: Protocol for a Second Large-Scale Double-Blind Randomized Clinical Trial to Optimize Stimulation Parameters

“…This study protocol is designed to confirm and potentially enhance, through further stimulation optimization, the clinical efficacy demonstrated in a recently completed clinical trial (Treatment Evaluation of Neuromodulation for Tinnitus - Stage A1 [TENT-A1]) that evaluated bimodal neuromodulation in 326 tinnitus participants. The TENT-A1 protocol has been previously published [59]. TENT-A1 was a double-blind, two-site randomized study that evaluated the relative efficacy and safety of three different settings for acoustic and trigeminal stimulation (ie, settings related to acoustic frequencies and background noise, electrical stimulation patterns on the tongue with a 32-site surface electrode array, and intermodality delays).…”