Unification of Treatments and Interventions for Tinnitus Patients (UNITI): a study protocol for a multi-center randomized clinical trial
Authors: Schoisswohl Stefan , Langguth Berthold , Schecklmann Martin , Bernal-Robledano Alberto , Boecking Benjamin , Cederroth Christopher R. , Chalanouli Dimitra , Cima Rilana , Denys Sam , Dettling-Papargyris Juliane , Escalera-Balsera Alba , Espinosa-Sanchez Juan Manuel , Gallego-Martinez Alvaro , Giannopoulou Efi , Hidalgo-Lopez Leyre , Hummel Michael , Kikidis Dimitris , Koller Michael , Lopez-Escamez Jose A. , Marcrum Steven C. , Markatos Nikolaos , Martin-Lagos Juan , Martinez-Martinez Maria , Martinez-Martinez Marta , Ferron Maria Mata , Mazurek Birgit , Mueller-Locatelli Nicolas , Neff Patrick , Oppel Kevin , Perez-Carpena Patricia , Robles-Bolivar Paula , Rose Matthias , Schiele Tabea , Schiller Axel , Simoes Jorge , Stark Sabine , Staudinger Susanne , Stege Alexandra , Verhaert Nicolas , Schlee Winfried 
Published: December 2021

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.