Unification of Treatments and Interventions for Tinnitus Patients (UNITI): a study protocol for a multi-center randomized clinical trial

Stefan Schoisswohl, Berthold Langguth, Martin Schecklmann, Alberto Bernal-Robledano, Benjamin Boecking, Christopher R Cederroth, Dimitra Chalanouli, Rilana Cima, Sam Denys, Juliane Dettling-Papargyris, Alba Escalera-Balsera, Juan Manuel Espinosa-Sanchez, Alvaro Gallego-Martinez, Efi Giannopoulou, Leyre Hidalgo-Lopez, Michael Hummel, Dimitris Kikidis, Michael Koller, Jose A Lopez-Escamez, Steven C Marcrum, Nikolaos Markatos, Juan Martin-Lagos, Maria Martinez-Martinez, Marta Martinez-Martinez, Maria Mata Ferron, Birgit Mazurek, Nicolas Mueller-Locatelli, Patrick Neff, Kevin Oppel, Patricia Perez-Carpena, Paula Robles-Bolivar, Matthias Rose, Tabea Schiele, Axel Schiller, Jorge Simoes, Sabine Stark, Susanne Staudinger, Alexandra Stege, Nicolas Verhaert, Winfried Schlee, Stefan Schoisswohl, Berthold Langguth, Martin Schecklmann, Alberto Bernal-Robledano, Benjamin Boecking, Christopher R Cederroth, Dimitra Chalanouli, Rilana Cima, Sam Denys, Juliane Dettling-Papargyris, Alba Escalera-Balsera, Juan Manuel Espinosa-Sanchez, Alvaro Gallego-Martinez, Efi Giannopoulou, Leyre Hidalgo-Lopez, Michael Hummel, Dimitris Kikidis, Michael Koller, Jose A Lopez-Escamez, Steven C Marcrum, Nikolaos Markatos, Juan Martin-Lagos, Maria Martinez-Martinez, Marta Martinez-Martinez, Maria Mata Ferron, Birgit Mazurek, Nicolas Mueller-Locatelli, Patrick Neff, Kevin Oppel, Patricia Perez-Carpena, Paula Robles-Bolivar, Matthias Rose, Tabea Schiele, Axel Schiller, Jorge Simoes, Sabine Stark, Susanne Staudinger, Alexandra Stege, Nicolas Verhaert, Winfried Schlee

Abstract

Background: Tinnitus represents a relatively common condition in the global population accompanied by various comorbidities and severe burden in many cases. Nevertheless, there is currently no general treatment or cure, presumable due to the heterogeneity of tinnitus with its wide variety of etiologies and tinnitus phenotypes. Hence, most treatment studies merely demonstrated improvement in a subgroup of tinnitus patients. The majority of studies are characterized by small sample sizes, unstandardized treatments and assessments, or applications of interventions targeting only a single organ level. Combinatory treatment approaches, potentially targeting multiple systems as well as treatment personalization, might provide remedy and enhance treatment responses. The aim of the present study is to systematically examine established tinnitus therapies both alone and in combination in a large sample of tinnitus patients. Further, it wants to provide the basis for personalized treatment approaches by evaluating a specific decision support system developed as part of an EU-funded collaborative project (Unification of treatments and interventions for tinnitus patients; UNITI project).

Methods/study design: This is a multi-center parallel-arm randomized clinical trial conducted at five different clinical sites over the EU. The effect of four different tinnitus therapy approaches (sound therapy, structured counseling, hearing aids, cognitive behavioral therapy) applied over a time period of 12 weeks as a single or rather a combinatory treatment in a total number of 500 chronic tinnitus patients will be investigated. Assessments and interventions are harmonized over the involved clinical sites. The primary outcome measure focuses on the domain tinnitus distress assessed via the Tinnitus Handicap Inventory.

Discussion: Results and conclusions from the current study might not only provide an essential contribution to combinatory and personalized treatment approaches in tinnitus but could also provide more profound insights in the heterogeneity of tinnitus, representing an important step towards a cure for tinnitus.

Trial registration: ClinicalTrials.gov NCT04663828 . Registered on 11 December 2020.

Keywords: Cognitive behavioral therapy; Hearing aids; Multi-center; RCT; Sound therapy; Structured counseling; Tinnitus; Treatment.

Conflict of interest statement

The authors declare that they have no conflict of interest associated with this publication and there has been no significant financial support that could influence the conduction of the RCT. The used hearing aid devices are provided by Sivantos Pte. Ltd/ WSAudiology. The devices for the measurement of acoustic evoked potentials are provided by Interacoustic A/S. There is no influence of any company or authority on the design, conduction, analysis, or any other details of this RCT. One employee of Sivantos Pte. Ltd/ WSAudiology is part of the External Advisory Board of the UNITI project [38], but has no influence on the conduction of the RCT. The results of the study are only made available to companies or external authorities via peer-reviewed publications.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Study procedure. An overview of all study visits/ measurement points plus the corresponding time periods between the visits is illustrated. For each study visit, a deviation of ± 7 days is allowed. In order to preselect potentially appropriate participants, an online pre-screening precedes the actual screening. Screening and baseline can be performed on the same day. Baseline has to be done at maximum 4 weeks before treatment start; otherwise, there will be an extraordinary visit. An additional follow-up visit 48 weeks after baseline can be conducted on a voluntary basis. Blood samples can be taken at any time point before treatment start (after informed consent) and is not mandatory for participation in the UNITI-RCT
Fig. 2
Fig. 2
Randomization. Eligible participants will be stratified according to their level of tinnitus distress and their level of hearing loss. In a first step, stratification will be conducted based on the THI score into a low and high tinnitus distress group. In the following step 2, participants’ hearing level will be used for stratification into one group with and one group without a hearing aid indication. Patients, who are already wearing a hearing aid for 3 months before screening are automatically allocated to the no hearing aid indication group. In a final step, participants will be randomly allocated to a treatment arm comprised of single or combinatory interventions

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