The statistical analysis plan for the unification of treatments and interventions for tinnitus patients randomized clinical trial (UNITI-RCT).

BACKGROUND: Tinnitus is a leading cause of disease burden globally. Several therapeutic strategies are recommended in guidelines for the reduction of tinnitus distress; however, little is known about the potentially increased effectiveness of a combination of treatments and personalized treatments for each tinnitus patient. METHODS: Within the Unification of Treatments and Interventions for Tinnitus Patients project, a multicenter, randomized clinical trial is conducted with the aim to compare the effectiveness of single treatments and combined treatments on tinnitus distress (UNITI-RCT). Five different tinnitus centers across Europe aim to treat chronic tinnitus patients with either cognitive behavioral therapy, sound therapy, structured counseling, or hearing aids alone, or with a combination of two of these treatments, resulting in four treatment arms with single treatment and six treatment arms with combinational treatment. This statistical analysis plan describes the statistical methods to be deployed in the UNITI-RCT. DISCUSSION: The UNITI-RCT trial will provide important evidence about whether a combination of treatments is superior to a single treatment alone in the management of chronic tinnitus patients. This pre-specified statistical analysis plan details the methodology for the analysis of the UNITI trial results. TRIAL REGISTRATION: ClinicalTrials.gov NCT04663828 . The trial is ongoing. Date of registration: December 11, 2020. All patients that finished their treatment before 19 December 2022 are included in the main RCT analysis.

Pilot study of a smartphone-based tinnitus therapy using structured counseling and sound therapy: A multiple-baseline design with ecological momentary assessment.

Tinnitus affects a considerable part of the population and develops into a severe disorder in some sufferers. App-based interventions are able to provide low-threshold, cost-effective, and location-independent care for tinnitus patients. Therefore, we developed a smartphone app combining structured counseling with sound therapy and conducted a pilot study to evaluate treatment compliance and symptom improvement (trial registration: DRKS00030007). Outcome variables were Ecological Momentary Assessment (EMA) measured tinnitus distress and loudness and Tinnitus Handicap Inventory (THI) at baseline and final visit. A multiple-baseline design with a baseline phase (only EMA) followed by an intervention phase (EMA and intervention) was applied. 21 patients with chronic tinnitus (≥ 6 months) were included. Overall compliance differed between modules (EMA usage: 79% of days, structured counseling: 72%, sound therapy: 32%). The THI score improved from baseline to final visit indicating a large effect (Cohens d = 1.1). Tinnitus distress and loudness did not improve significantly from baseline phase to the end of intervention phase. However, 5 of 14 (36%) improved clinically meaningful in tinnitus distress (ΔDistress ≥ 10) and 13 of 18 (72%) in THI score (ΔTHI ≥ 7). The positive relationship between tinnitus distress and loudness weakened over the course of the study. A trend but no level effect for tinnitus distress could be demonstrated by a mixed effect model. The improvement in THI was strongly associated with the improvement scores in EMA of tinnitus distress (r = -0.75; 0.86). These results indicate that app-based structured counseling combined with sound therapy is feasible, has an impact on tinnitus symptoms and reduces distress for several patients. In addition, our data suggest that EMA could be used as a measurement tool to detect changes in tinnitus symptoms in clinical trials as has already been shown in other areas of mental health research.

The Influence of Diet on Tinnitus Severity: Results of a Large-Scale, Online Survey.

Optimization of dietary intake is an essential component in the multidimensional effort to prevent and manage chronic disease. Recently, demand has increased for nutrition-focused management strategies for chronic tinnitus. The primary aim of this study was to evaluate 10 dietary items for their association with changes in subjective tinnitus severity. A secondary aim was to develop an algorithm to better identify those individuals who might benefit from dietary modification strategies. A total of 5017 anonymous users of the TinnitusTalk forum completed an online survey regarding how various dietary items affected the severity of their tinnitus. Results suggest that, while intake of caffeine [positive effect (PE): 0.4%; negative effect (NE): 16.2%], alcohol (PE: 2.7%; NE: 13.3%, and salt (PE: 0.1%; NE: 9.9%) was most likely to influence tinnitus severity, it did so only for a small proportion of participants and reported effects were most commonly mild. Further, though a classification algorithm was able to leverage participant demographic, comorbidity, and tinnitus characteristics to identify those individuals most likely to benefit from dietary modification above chance levels, further efforts are required to achieve significant clinical utility. Taken together, these results do not support dietary modification as a primary treatment strategy for chronic tinnitus in the general population, though clinically meaningful effects might be observable in certain individuals.

UNITI Mobile-EMI-Apps for a Large-Scale European Study on Tinnitus.

More and more observational studies exploit the achievements of mobile technology to ease the overall implementation procedure. Many strategies like digital phenotyping, ecological momentary assessments or mobile crowdsensing are used in this context. Recently, an increasing number of intervention studies makes use of mobile technology as well. For the chronic disorder tinnitus, only few long-running intervention studies exist, which use mobile technology in a larger setting. Tinnitus is characterized by its heterogeneous patient's symptom profiles, which complicates the development of general treatments. In the UNITI project, researchers from different European countries try to unify existing treatments and interventions to cope with this heterogeneity. One study arm (UNITI Mobile) exploits mobile technology to investigate newly implemented interventions types, especially within the pan-European setting. The goals are to learn more about the validity and usefulness of mobile technology in this context. Furthermore, differences among the countries shall be investigated. Practically, two native intervention apps have been developed for UNITI and the mobile study arm, which pose features not presented so far in other apps of the authors. Along the implementation procedure, it is discussed whether these features might leverage similar types of studies in future. Since instruments like the mHealth evidence reporting and assessment checklist (mERA), developed by the WHO mHealth technical evidence review group, indicate that aspects shown for UNITI Mobile are important in the context of health interventions using mobile phones, our findings may be of a more general interest and are therefore being discussed in the work at hand.