Influence of Treatment Duration and Stimulation Frequency on rTMS in Chronic Tinnitus

Study Overview
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Brief Summary
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Patients receive two weeks of treatment (prefrontal high-frequency and bilateral low-frequency rTMS vs. prefrontal high-frequency and bilateral high-frequency rTMS). After two weeks of treatment they can decide if they want to quit the treatment or if they want to proceed with the treatment for another two weeks.

Detailed Description
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Tinnitus is the phantom auditory perception of sound in the absence of an external or internal acoustic stimulus. It is a frequent problem which can interfere significantly with the ability to lead a normal life. Tinnitus has been shown to be generated in the brain, as a result of functional reorganization of auditory and non-auditory neural pathways. Low-frequency repetitive transcranial magnetic stimulation (rTMS) applied to the temporoparietal areas has been investigated for the treatment of tinnitus based on the rationale to reduce increased activity of the auditory system. Furthermore, high-frequency stimulation of the left frontal cortex was added to this standard treatment based on rTMS studies in affective disorders and the association of tinnitus distress with depressivity. Thus, high-frequency stimulation of the left prefrontal cortex and low-frequency stimulation of bilateral temporoparietal cortex was introduced as new treatment scheme in chronic tinnitus (multisite standard). Additionally, there is also evidence that high-frequency stimulation of the temporoparietal cortex is effective in chronic tinnitus. Furthermore, standard treatment in chronic tinnitus is two weeks (ten treatment days) which is shorter than the standard in rTMS in affective disorders. Thus, the aim of the present trial is to investigate the influence of high-frequency stimulation of the temporoparietal cortex and of increasing the number of treatment days. Patients receive two weeks of treatment (prefrontal high-frequency and bilateral low-frequency rTMS vs. prefrontal high-frequency and bilateral high-frequency rTMS). After two weeks of treatment they can decide if they want to quit the treatment or if they want to proceed with the treatment for another two weeks.

Official Title
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Influence of Treatment Duration and Stimulation Frequency on Repetitive Transcranial Magnetic Stimulation in Chronic Tinnitus

Conditions
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Chronic Tinnitus

Intervention / Treatment
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* Other: standard multisite four weeks
* Other: high-frequency multisite four weeks
* Other: standard multisite two weeks
* Other: high-frequency multisite two weeks


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: written informed consent duration of tinnitus more than 6 months bothersome chronic tinnitus Exclusion Criteria: not stable internal, mental, and neurological diseases contraindication for rTMS (pacemaker, metal implants, pregnancy, epilepsy, status post severe craniocerebral injury ) uninvolvement in other treatment studies for tinnitus at the same time

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: standard multisite four weeks<br>Combined high-frequency dorsolateral prefrontal (unilateral) and low frequency temporoparietal (bilateral) stimulation; complete treatment of four weeks | Other: standard multisite four weeks<br>* Repetitive transcranial magnetic stimulation (Magventure): 1000 stimuli of 20 Hz rTMS over the left DLPFC (110% motor threshold) followed by 1000 stimuli of 1 Hz rTMS over the left temporoparietal cortex (110% motor threshold) followed by 1000 stimuli of 1 Hz rTMS over right temporoparietal cortex (110% motor threshold). Patients continue treatment after two weeks for further two weeks of treatment (20 treatment days).<br>|
| Experimental: high-frequency multisite four weeks<br>Combined high-frequency dorsolateral prefrontal (unilateral) and high-frequency temporoparietal (bilateral) stimulation; complete treatment of four weeks | Other: high-frequency multisite four weeks<br>* Repetitive transcranial magnetic stimulation (Magventure): 1000 stimuli of 20 Hz rTMS over the left DLPFC (110% motor threshold) followed by 1000 stimuli of 20 Hz rTMS over the left temporoparietal cortex (110% motor threshold) followed by 1000 stimuli of 20 Hz rTMS over right temporoparietal cortex (110% motor threshold). Patients continue treatment after two weeks for further two weeks of treatment (20 treatment days).<br>|
| Experimental: standard multisite two weeks<br>Combined high-frequency dorsolateral prefrontal (unilateral) and low frequency temporoparietal (bilateral) stimulation; discontinuation after two weeks | Other: standard multisite two weeks<br>* Repetitive transcranial magnetic stimulation (Magventure): 1000 stimuli of 20 Hz rTMS over the left DLPFC (110% motor threshold) followed by 1000 stimuli of 1 Hz rTMS over the left temporoparietal cortex (110% motor threshold) followed by 1000 stimuli of 1 Hz rTMS over right temporoparietal cortex (110% motor threshold). Patients discontinue treatment after two weeks (10 treatment days).<br>|
| Experimental: high-frequency multisite two weeks<br>Combined high-frequency dorsolateral prefrontal (unilateral) and high-frequency temporoparietal (bilateral) stimulation; discontinuation after two weeks | Other: high-frequency multisite two weeks<br>* Repetitive transcranial magnetic stimulation (Magventure): 1000 stimuli of 20 Hz rTMS over the left DLPFC (110% motor threshold) followed by 1000 stimuli of 20 Hz rTMS over the left temporoparietal cortex (110% motor threshold) followed by 1000 stimuli of 20 Hz rTMS over right temporoparietal cortex (110% motor threshold). Patients discontinue treatment after two weeks (10 treatment days).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in tinnitus questionnaire | change in tinnitus questionnaire | week12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in tinnitus questionnaire | change in tinnitus questionnaire | week2, week3, week4, week12 | 
| change in tinnitus handicap inventory | change in tinnitus handicap inventory | week2, week3, week4, week12 | 
| change in tinnitus numeric rating scales | change in tinnitus numeric rating scales | week2, week3, week4, week12 | 
| change in major depression inventory | change in major depression inventory | week2, week3, week4, week12 | 
| change in clinical global impression | change in clinical global impression | week2, week3, week4, week12 | 
| change in quality of life | change in quality of life | week2, week3, week4, week12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tinnitus, transcranial random noise stimulation, rTMS, multisite stimulation, non-invasive brain stimulation