UNification of Treatments and Interventions for TInnitus Patients - Randomized Clinical Trial (UNITI-RCT)

Overview

The study includes a 12-week treatment trial for chronic tinnitus patients using 4 different types of interventions (hearing aids, sound therapy, structured counseling, cognitive behavioral therapy) either as a single treatment or a combination of two treatments. There are several aims of the study: compare 1) single vs. combined treatments, 2) single treatments vs. other treatments, 3) ear and brain based interventions, 4) analyzing data of the clinical trial in combination with other recorded data (genetic and proteomic data, audiology data) to develop in silico models of tinnitus and a decision support system with the aim to aid in treatment decisions. This randomized controlled trial is harmonized over five clinical centers in Europe with the aim to include 100 patients per center and is part of the UNITI-project (UNification of treatments and Interventions for TInnitus patients) funded by the European Union's Horizon 2020 programme (grant agreement number 848261).

The study will be conducted as a randomized controlled trial (RCT), which investigates the effect of four different tinnitus therapy approaches applied over a time period of 12 weeks as a single or rather a combinatory treatment in 100 chronic tinnitus patients. The protocol of the RCT is harmonized over five clinical centers across Europe with each center responsible for study procedures (regulations with respect to CGP, GDPR etc.) themselves. Thus, the present protocol is for the Regensburg part of the study. Used therapies are - hearing aid (HA), sound therapy (ST), structured counseling (SC) and cognitive behavioral therapy for tinnitus (CBT4T). HA fitting will be conducted with CE-marked hearing aids from Signia Hearing Aids (Sivantos Pte. Ltd., Singapore, Republic of Singapore/ WSAudiology, Lynge, Denmark) with respect to patients hearing profile according to a standardized procedure. ST will be performed via a specifically developed mobile application (according to the European regulations for medical software (IEC 62304, IEC 82304)). Patients can select among 64 standardized or individualized (according to their tinnitus characteristics) sounds presented at a maximum loudness of 85 dB. A standardized SC protocol will be provided via a mobile application (preferably), URL-links, e-mail or in printed form over a 12-week treatment period including 12 chapters (one per week). CBT4T will be held on a weekly basis in groups not bigger than 6 patients á 1.5-2 hours. All interventions will be carried out by staff with corresponding expertise (e.g., audiologist or psychologists) or specially trained study assistants by these experts. Prior to the start of the study, potential participants will be online pre-screened with respect to inclusion and exclusion criteria. If the potential candidates are appropriate for a participation, they will be invited for a first visit on-site for a detailed screening of inclusion and exclusion criteria, and of health-related, tinnitus-specific, audiological examinations and electrophysiological measurements (auditory brainstem response, auditory middle latency response). Based on their determined hearing profile the decision will be made, whether there is an indication for the application of a HA. Accordingly, the sample of patients will be stratified into two groups: patients with an HA indication and those without an indication. If such a HA indication does not exist, patients will alternatively receive ST. Within these two groups (hearing aid indication - yes or no), patients will be randomly allocated to the intervention arms consisting of single and combinational interventions. Single therapy: * HA (in the group stratified for hearing aids) * ST * SC * CBT4T Combinational therapy: * HA + ST (in the group stratified for hearing aids) * HA + SC (in the group stratified for hearing aids) * HA + CBT4T (in the group stratified for hearing aids) * ST + SC * ST + CBT4T * SC + CBT4T Screening and baseline as well as treatment start can be performed on the same day. In this case relevant assessments are only performed once. In addition, blood samples can be obtained during screening, baseline or a separate visit before treatment begin. Blood sampling is voluntary and does not have influence on participation of the study. After the baseline visit the respective intervention will start (at latest 4 weeks after the baseline, otherwise baseline measurements will be repeated) and last for 12 weeks. During an interim assessment after 6 weeks of treatment participants have to complete health-related and tinnitus-specific questionnaires again plus additional assessments of adverse events. Interventions will end after 12 weeks with a repetition of measurements made during baseline and another evaluation of adverse events. A follow-up measurement is planned 9 months after the first visit (baseline measurement). Moreover, an additional voluntary follow-up assessment can be done 12 months after the first visit. Each visit will have a duration of approximately 2-3 hours. Our primary outcome will focus on changes in tinnitus distress measured via the Tinnitus Handicap Inventory (THI; (Newman et al., 1996)). Participants can choose to cancel their participation in the study at any point without reasons or any disadvantages except the missing treatment. Intervention for a single participant can be cancelled in the case of a significant deterioration of tinnitus symptoms. Slight worsening might be possible but expected to short-term. In case of worsening, participants receive support by trained medical and psychological experts. Prior to the start of the study, it will be registered in clinicaltrials.gov. For detailed information about the study procedure, interventions and used measurement please see the attached "UNITI - clinical investigation plan". Sample A planned sample size of N = 100 patients in Regensburg will be recruited from the clinic and polyclinic for ear, nose and throat medicine as well as from the clinic and polyclinic for psychiatry and psychotherapy both part of the University of Regensburg. Additional recruitment strategies such as marketing via newspaper etc. are planned.