Verify the Effectiveness rTMS Using MEG

Study Overview
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Brief Summary
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The purpose of this study is to determine whether rTMS are effective in the treatment of tinnitus

Detailed Description
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Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) has an add-on effect for primary auditory cortex rTMS in improving tinnitus-related distress. We aimed to investigate whether rTMS of the dorsolateral prefrontal cortex and primary auditory cortex are capable of reducing tinnitus loudness. Linked to a neuronavigation system that is guided by magnetic resonance imaging (MRI) of the frontal and temporal, rTMS can suppress areas of cortical plasticity. This cortical reorganization can be demonstrated by magnetoencephalography (MEG)

Official Title
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Verify the Effectiveness rTMS Using MEG

Conditions
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Tinnitus

Intervention / Treatment
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* Device: 1
* Device: 2
* Device: 3
* Device: 4


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of chronic tinnitus Chronic subjective tinnitus for more than 6 months Pure tone average <50 dB HL in the ear where tinnitus is perceived Dominant tinnitus frequency measured between 4 and 8 kHz Subject is naive regarding rTMS Other concurrent treatments: A four-week washout from any other tinnitus treatment or management program is required prior to entering this study Stable enough to complete this study per the opinion of the Study Physician No restrictions, provided the dosages have been in place for at least 3 months A three month washout from any other tinnitus treatment or management program is required prior to entering this study. Exclusion Criteria: Objective tinnitus or tinnitus with treatable cause Absolute thresholds > 60 dB on individual frequencies up to 8 kHz Presence of intracranial or intraocular ferromagnetic materiel or particles Cardiac pacemaker or other electronic implants (including cochlear implant) Serious heart disease or other unstable major medical condition Personal history of central nervous system disorder, head injury, stroke or seizures Familial history of epilepsy; Concomitant medication with antidepressants and antipsychotics Pregnant women Severe depression Severe anxiety Others known contraindications to rTMS or brain MRI

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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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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active rTMS1<br>Combined low frequency frontal and temporal repetitive transcranial magnetic stimulation of left primary auditory cortex and left dorsolateral prefrontal cortex . | Device: 1<br>* repetitive transcranial magnetic stimulation (Figured 8-Coil MCF-B65): 1000 stimuli of 1Hz rTMS over the left DLPFC (110% motor threshold) followed by 2000 stimuli of 1 Hz rTMS over the left temporal cortex (110% motor threshold), each consisting of 4 days of rTMS treatment. Participants will have an MRI scan and MEG recoding at the performed a week before rTMS. And MEG recording after 7day the application of rTMS<br>|
| Experimental: Active rTMS2<br>Temporal low frequency rTMS of left primary auditory cortex. | Device: 2<br>* repetitive transcranial magnetic stimulation (Figured 8-Coil MCF-B65): 3000 stimuli of 1 Hz rTMS over the left temporal cortex (110% motor threshold), each consisting of 4 days of rTMS treatment. Participants will have an MRI scan and MEG recoding at the performed a week before rTMS. And MEG recording after 7day the application of rTMS.<br>|
| Experimental: Active rTMS3<br>Frontal low frequency rTMS of left dorsolateral prefrontal cortex . | Device: 3<br>* repetitive transcranial magnetic stimulation (Figured 8-Coil MCF-B65): 3000 stimuli of 1 Hz rTMS over the left frontal cortex (110% motor threshold) each consisting of 4 days of rTMS treatment. Participants will have an MRI scan and MEG recoding at the performed a week before rTMS. And MEG recording after 7day the application of rTMS.<br>|
| Sham Comparator: Sham rTMS4<br>sham treatment Sham rTMS, applied with the same combination of parameters as active rTMS, except for the number of stimulations per session. | Device: 4<br>* Sham rTMS, applied with the same combination of parameters as active rTMS, except for the number of stimulations per session. Participants will have an MRI scan and MEG recoding at the performed a week before rTMS. And MEG recording after 7day the application of rTMS.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in MEG Asymmetry Index and amplitude of the auditory area |  | Baseline, After active treatment week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tinnitus Handicap Inventory (THI) |  | Baseline, day 3, day 7, day 14, 1, 2 and 3 months after the first intervention | 
| Visual Analog Scales (VAS) |  | Baseline, day 3, day 7, day 14, 1, 2 and 3 months after the first intervention | 
| State-Trait Anxiety Inventory (STAI) |  | Baseline, before and after each intervention, 1, 2 and 3 months after the first intervention | 
| Pittsburgh Sleep Quality Index (PSQI) |  | Baseline, before and after each intervention, 1, 2 and 3 months after the first intervention | 
| Beck Depression Inventory (BDI) |  | Baseline, before and after each intervention, 1, 2 and 3 months after the first intervention |