Deep Repetitive Transcranial Magnetic Stimulation in the Treatment of Tinnitus

A two-week treatment study is planned to investigate the effectiveness of different deepTMS coils in the treatment of tinnitus. The study plans to enroll 60 patients with chronic subjective tinnitus. Recruitment will take place primarily through the affiliated interdisciplinary Tinnitus Center in Regensburg, as well as through posters or flyers at private practice physicians' offices and hearing aid specialists. After successful screening, standard audiological measurements (hearing threshold, tinnitus matching, etc.) and verification of the inclusion and exclusion criteria, study participants will be randomized into one of three treatment groups, each consisting of 20 patients: (1) 18 Hz deepTMS with the H1 coil; (2) 1 Hz deepTMS with the H4 coil; (3) 18 Hz placebo deepTMS with the H7 coil.

Two groups receive active deepTMS treatment, while the third group receives a placebo stimulation. The RCT version of the BrainsWay H7 coil is used for the placebo treatment. The placebo coil is integrated into the same stimulation helmet as the active treatment coil. The placebo stimulation generates acoustic and somatosensory stimuli comparable to those of the active stimulation but does not induce an electric field strong enough for therapeutic cortical stimulation.

The study plans to compare the H1 coil with the H4 coil. Furthermore, the treatment effects will be compared with a placebo treatment as well as with a matched historical control group of patients who were treated with conventional left temporal low-frequency rTMS at the Center for Neuromodulation at the University of Regensburg. The treatment phase corresponds to a standard rTMS treatment for tinnitus and consists of 10 weekday stimulation sessions over two weeks, with 2,000 pulses per session. Before treatment begins, each patient's individual resting motor threshold (RMT) is determined; this is used to set the stimulation intensity for the treatment. The stimulation intensity is gradually increased over the course of the first three treatment sessions from 100% to a maximum of 120% of the RMT. If the stimulation is perceived by the patients as too unpleasant or painful, the intensity is not increased further; treatment continues at the intensity level individually tolerated by each patient. Before and after the 2-week treatment period, patients are given several standardized tinnitus and health questionnaires, and standard audiological measurements are performed. In addition, a follow-up visit is scheduled ten weeks after the end of treatment to assess any potential lasting effects of the treatment. The following questionnaires are used:

* The European School for Interdisciplinary Tinnitus Research Screening Questionnaire (ESIT-SQ)
* Tinnitus Sample Case History Questionnaire (TSCHQ)
* Tinnitus Handicap Inventory (THI)
* Tinnitus Functional Index (TFI)
* Mini Tinnitus Questionnaire (mini-TQ)
* Tinnitus Analogscales
* Major Depression Inventory (MDI )
* WHO-Quality of Life (WHOQoL-BREF)
* Clinical Global Impression Scale - Improvement (CGI-I) The primary endpoint is defined as the change in the Tinnitus Handicap Inventory (THI) from baseline (before treatment begins) to the end of treatment, as well as a comparison of this change between the treatment groups. Participants are also asked to rate the loudness of their tinnitus before and after active or placebo stimulation, respectively, in order to assess short-term changes in tinnitus perception. Patients in the placebo group will be given the opportunity to receive active treatment after the study is completed. This consists of a 10-day treatment course with 2,000 pulses per session using the H7 coil and an 18 Hz protocol.

There are no plans to calculate the required sample size, as only a single-case trial using deepTMS for tinnitus has been conducted to date. In addition, different coil geometries are used compared to conventional TMS studies. Therefore, it is difficult to estimate the potential effect size.

• DeepTms (Device): 2 weeks deepTMS with different H-coils, 2000 pulses per session, Follow Up 10 weeks after treatment end

Primary outcomes

• Changes in Tinnitus Burden [12 weeks: from enrollment to the end of treatment after two weeks, plus Follow Up after 10 weeks]: Changes in Tinnitus Burden Measured Using the Tinnitus Handicap Inventory (THI) from Baseline to the End of Treatment, Including Group Comparisons. The THI consists of 25 items designed to evaluate the perceived impact of tinnitus on an individual's daily life. Each item provides three response options: 'No', 'Sometimes' and 'Yes', which are scored as 0, 2 and 4 points respectively. The total THI score is obtained by summing the scores of all items, resulting in a score that ranges from 0 to 100, with higher scores indicating greater perceived handicap due to tinnitus.

Secondary outcomes

• Tinnitus Functional Index (TFI) [12 weeks: from enrollment to end of treatment after 2 weeks, plus Follow Up after 10 weeks]: Changes in TFI: The TFI measures the functional impact of tinnitus and consists of 25 items. It includes 8 subscales: cognitive interference, auditory perceptual difficulties, intrusiveness, sleep disturbances, disturbances of relaxation, quality of life impairment, emotional distress, and reduced sense of control. The total score ranges from 0 and 100. A lower score indicates greater perceived distress due to tinnitus.
• Tinnitus loudness [12 weeks: from enrollment to end of treatment after 2 weeks, plus Follow Up after 10 weeks]: short-term changes in tinnitus loudness, ranging from 0% to 200% (0%=no tinnitus perception, 50% = half of the usually perceived tinnitus loudness, 100% usually perceived tinnitus loudness, 200%=twice as loud as usually perceived tinnitus loudness
• Clinical Global Inventory - Improvement Scale [end of treatment after two weeks, plus Follow Up after 10 weeks]: Within 1 question, patients are asked to rate the overall improvement of their tinnitus complaints compared to before the treatment has started on a 7-point Likert scale (1-"very much better," 2-"much better," 3-"minimally better," 4-"no change," 5-"minimally worse," 6-"much worse," 7-"very much worse").
• Mini-Tinnitus Questionnaire (Mini-TQ) [12 weeks: from enrollment to end of treatment after 2 weeks, plus Follow Up after 10 weeks]: The Mini-TQ is a validated, 12-item patient-reported outcome measure designed to assess tinnitus-related psychological distress and its impact on daily life. Each item is scored on a 3-point scale: true (2 points), partly true (1 point), or not true (0 points), yielding a total score of 0-24, with higher scores indicating greater tinnitus-related distress.
• Major Depression Inventory (MDI) [12 weeks: from enrollment to end of treatment after 2 weeks, plus Follow Up after 10 weeks]: The MDI is a validated 10-item self-report questionnaire assessing depressive symptoms. Items are rated from 0 (at no time) to 5 (all the time). For items 8 and 10, the higher sub-item score is used. The total score ranges from 0-50, with higher scores indicating greater depressive symptom severity.
• Tinnitus Analogue Scales [12 weeks: from enrollment to end of treatment after 2 weeks, plus Follow Up after 10 weeks]: Participants rate the loudness of their tinnitus (0-not at all loud; 10-extremely loud), the tinnitus-induced discomfort (0-no discomfort; 10-severe discomfort), annoyance (0-not at all annoying; 10-extremely annoying), unpleasantness (0-not at all unpleasant; 10-extremely unpleasant) as well as the possibility to ignore their tinnitus (0-very easy to ignore; 10-impossible to ignore) on a Visual Analog Scale (VAS).
• World Health Organization-Quality of Life instrument (WHOQOL-BREF) [12 weeks: from enrollment to end of treatment after 2 weeks, plus Follow Up after 10 weeks]: A 26-item validated, self-report questionnaire assessing quality of life across four domains: physical health (items 3, 4, 10, 15-18), psychological health (items 5-7, 11, 19, 26), social relationships (items 20-22), and environment (items 8, 9, 12-14, 23-25). Items 1 and 2 assess overall quality of life and general health, respectively. Scoring: Items are rated on a 5-point scale (1-5). Domain scores are transformed to a 4-20 or 0-100 scale, with higher scores indicating better quality of life. Items 3, 4, and 26 are reverse-scored.

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

* Chronic tinnitus (> 6 months)
* Moderate tinnitus burden-corresponding to a score of ≥ 18 on the Tinnitus Handicap Inventory
* Stable medication regimen with psychoactive substances

Exclusion Criteria:

* Objective tinnitus
* Severe and unstable internal medicine, neurological, and psychiatric comorbidities (particularly acute psychosis, severe depression, or substance dependence; epilepsy; brain tumor; encephalitis; history of traumatic brain injury)
* Presence of contraindications for TMS (electrical implants or metallic objects in the body, such as a pacemaker or insulin pump)
* Currently undergoing or planning to undergo tinnitus treatment during the study
* Meniere's disease, otosclerosis, acoustic neuroma, or other clear-cut or treatment-requiring causes of tinnitus

• Salviati M, Bersani FS, Calabria LF, Rapinesi C, Kotzalidis GD, Minichino A, Romano A, Moraschi M, Chiacchiararelli L, Bozzao A, Cianfrone G, Girardi P. Deep transcranial magnetic stimulation in a woman with chronic tinnitus: clinical and FMRI findings. Seeking relief from a symptom and finding vivid memories by serendipity. Brain Stimul. 2014 May-Jun;7(3):492-4. doi: 10.1016/j.brs.2014.02.005. Epub 2014 Feb 20. No abstract available. PMID 24685051

• Stefan Schoisswohl, Prof. Dr. hum sc, Principal investigator, Psychiatry and Psychotherapie University Regensburg