rTMS for the Treatment of Chronic Tinnitus: Optimization by Simulation of the Cortical Tinnitus Network

Study Overview
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Brief Summary
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Transcranial Magnetic Stimulation is used to modulate both the auditory and non-auditory neural pathways contributing to the perception of phantom sounds.

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. Treatment remains difficult. Most available therapies focus on habituation rather than treating the cause. Tinnitus has been shown to be associated with functional reorganization of auditory neural pathways and tonotopic maps in the central auditory system. Consequently, low-frequency Repetitive Transcranial Magnetic Stimulation (rTMS) applied to the temporoparietal areas has been investigated for the treatment of tinnitus. Additionally, there is growing evidence that a neural network of both auditory and non-auditory cortical areas is involved in the pathophysiology of chronic subjective tinnitus. Targeting several core regions of this network by rTMS might constitute a promising strategy to enhance treatment effects. A new multisite treatment protocol which is supposed to have an effect on both auditory and non-auditory cortical areas will be examined with regard to feasibility, safety and clinical efficacy in patients suffering from chronic tinnitus in a controlled pilot trial.

Official Title
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Repetitive Transcranial Magnetic Stimulation for the Treatment of Chronic Tinnitus: Optimization by Stimulation of the Cortical Tinnitus Network

Conditions
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Chronic Tinnitus

Intervention / Treatment
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* Device: rTMS intervention 1
* Device: rTMS intervention 2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of subjective chronic tinnitus THI > 38 Duration of tinnitus more than 6 months Exclusion Criteria: Objective tinnitus Treatable cause of the tinnitus Involvement in other treatments for tinnitus at the same time Clinically relevant psychiatric comorbidity Clinically relevant unstable internal or neurological comorbidity History of or evidence of significant brain malformation or neoplasm, head injury Cerebral vascular events Neurodegenerative disorder affecting the brain or prior brain surgery; Metal objects in and around body that can not be removed Pregnancy Alcohol or drug abuse Prior treatment with TMS

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: single site rTMS<br>Low frequency temporoparietal transcranial magnetic stimulation Intervention: Device: rTMS intervention 1 | Device: rTMS intervention 1<br>* Low frequency rTMS (Magventure Mag Pro Option) applied over left temporoparietal cortex: 3000 stimuli of 1Hz rTMS (110% motor threshold); 1 minute break after 1000 and 2000 stimuli. Arms: single site rTMS<br>|
| Experimental: multisite rTMS<br>Combined high frequency dorsolateral prefrontal (unilateral) and low frequency temporoparietal (bilateral) stimulation Intervention: Device: rTMS Intervention 2 | Device: rTMS intervention 2<br>* Repetitive transcranial magnetic stimulation (Magventure Mag Pro Option): 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). Arms: multisite rTMS<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of treatment responders (TQ reduction ≥5, contrast baseline versus day 12) |  | Day 12 | 
| Change of tinnitus severity as measured by the Tinnitus Questionnaire of Goebel&Hiller (contrast baseline versus day 12) |  | Day 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of depressive symptoms as measured by the Major Depression Inventory (MDI) |  | Day 12 | 
| Change in quality of life as measured by the WHOQoL |  | Day 12 | 
| Change in hyperacusis as measured by the German questionnaire Geräuschüberempfindlichkeitsfragebogen |  | Day 12 | 
| Number of treatment responders (TQ reduction ≥5, contrast Baseline versus day 90) |  | Day 90 | 
| Change of tinnitus severity as measured by the Tinnitus Handicap Inventory (THI) and Tinnitus Severity Scale |  | Day 12 | 
| Change of tinnitus severity as measured by the Tinnitus Handicap Inventory (THI) and Tinnitus Severity Scale |  | Day 90 | 
| Change of tinnitus severity as measured by the Tinnitus Handicap Inventory (THI) and Tinnitus Severity Scale |  | Day 180 | 
| Change of depressive symptoms as measured by the Major Depression Inventory (MDI) |  | Day 180 | 
| Change of depressive symptoms as measured by the Major Depression Inventory (MDI) |  | Day 90 | 
| Change in quality of life as measured by the WHOQoL |  | Day 90 | 
| Change in quality of life as measured by the WHOQoL |  | Day 180 | 
| Change in hyperacusis as measured by the German questionnaire Geräuschüberempfindlichkeitsfragebogen |  | Day 90 | 
| Change in hyperacusis as measured by the German questionnaire Geräuschüberempfindlichkeitsfragebogen |  | Day 180 | 
| Number of treatment responders (TQ reduction ≥5, contrast Baseline versus day 180) |  | Day 180 | 
| Change of tinnitus severity as measured by the Tinnitus Questionaire of Goebel&Hiller |  | Day 90 | 
| Change of tinnitus severity as measured by the Tinnitus Questionaire of Goebel&Hiller |  | Day 180 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tinnitus, chronic subjective Tinnitus, transcranial magnetic stimulation, rTMS, hearing disorders