Transcranial Magnetic Stimulation in Episodic Migraine (Magnet-EM)

Study Overview
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Brief Summary
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This study will assess the safety and efficacy of repetitive transcranial magnetic stimulation (rTMS) as new preventive treatment of migraine.

Detailed Description
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Migraine patients according to International Headache Society criteria will be allocated randomly into two treatment arms. One group will receive active rTMS and another group will receive sham rTMS for treatment phase (5 sessions). Assessment will be made at baseline, month 1, month 2 and month 3 post-treatment.

Official Title
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Effectiveness and Tolerability of Repetitive Transcranial Magnetic Stimulation For Preventive Treatment Of Episodic Migraine: A Single Centre, Randomised, Double-Blind, Sham-Controlled Phase 2 Trial

Conditions
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Migraine

Intervention / Treatment
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* Device: Repetitive Transcranial Magnetic Stimulation.
* Device: Sham rTMS


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Males or females aged 18 to 60 years of age. Subjects fulfilling criteria for episodic migraine as per the Third Edition of The International Headache Society (ICHD-3) for at least 1 year. Frequency of migraine attacks 2-8 times per month with less than 15 headache days per month for at least 3 months prior to screening. Demonstrated compliance with the headache diary during the run-in period by entry of headache data on a minimum of 24/30 days (80% compliance). A signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study including any known and potential risks and available alternative treatments. Exclusion criteria: Patients with previous history of rTMS treatment. Onset of headache at more than 50-year-old. Headache with red flags symptoms that may suggest organic secondary headaches. Pregnant or lactating women. Patients with contraindications to TMS such as metallic implant and pacemaker based on the Screening 13-item Questionnaire for rTMS candidate. Patients with medical conditions such severe hypertension, infections, malignancy, cardiovascular and cerebrovascular disease, epilepsy degenerative central nervous system diseases, renal failure, hepatic failure, bleeding diathesis and serious mental illness.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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
Interventional Model Description: Two-arm parallel assignment involves two groups of participants. One group receives r-TMS, and the other group receives sham placebo r-TMS.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: repetitive Transcranial Magnetic Stimulation<br>Magstim Rapid-2 (Whitland, Walsh, UK), 70mm Double Air Film Coil given on left dorsolateral prefrontal cortex for five sessions. | Device: Repetitive Transcranial Magnetic Stimulation.<br>* High frequency rTMS on left dorsolateral prefrontal cortex.<br>* Other names: rTMS;|
| Sham Comparator: Sham repetitive Transcranial Magnetic Stimulation<br>Magstim Rapid-2 (Whitland, Walsh, UK), 70mm Double Air Film Sham Coil given on left dorsolateral prefrontal cortex for five sessions. | Device: Sham rTMS<br>* Sham rTMS without active magnetic coil on left dorsolateral prefrontal cortex.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in mean monthly migraine days. | The mean monthly migraine days will be calculated using the monthly migraine days from each of the month of the double-blind treatment phase. | Baseline and month 1, 2 and 3 post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in mean monthly migraine attacks. | The mean monthly migraine attacks will be calculated using the monthly migraine attack from each of the month of the double-blind treatment phase. | Baseline and month 1, 2 and 3 post treatment | 
| Proportion of subjects with at least a 50% reduction from baseline in mean monthly migraine days. | Change from baseline in mean monthly pain intensity of migraine attacks. The mean monthly pain intensity will be based on the record of the maximal pain intensity by means of a verbal scale (i.e. 0 =no headache; 1 = mild headache; 2 = moderate headache; 3 = severe headache) prior to taking symptomatic medication. | Baseline and month 1, 2 and 3 post treatment | 
| Frequency and severity of adverse events in response to rTMS. | Recorded any adverse events as per Good Clinical Practice Guideline and Declaration of Helsinki. | During treatment and up until 1 month post treatment | 
| The Depression Anxiety Stress Scale (DASS 21) score changes in migraine patients in response to rTMS. | Mean score changes from baseline for depression, anxiety and stress category. | Baseline and at month 3 post treatment | 
| The Migraine Disability Assessment Test (MIDAS) score changes in migraine patients in response to rTMS. | Mean score changes from baseline. | Baseline and at month 3 post treatment | 
| The Migraine Specific Questionnaire (MSQ) version 2.1 score changes in migraine patients in response to r-TMS. | Mean score changes from baseline. | Baseline and at month 3 post treatment | 
| The EQ-5D score changes in migraine patients in response to rTMS. | Mean score changes from baseline. | Baseline and at month 3 post treatment | 
| The Pittsburgh Sleep Quality Index score changes in migraine in response to rTMS. | Mean score changes from baseline for sleep quality. | Baseline and at month 3 post treatment | 
| The Food Frequency Questionnaire score in migraine patients | Measuring food frequency intake at baseline | Baseline | 
| The Global Physical Activity Questionnaire score change in migraine in response to rTMS. | Mean score changes from baseline. | Baseline and at month 3 post treatment | 
| Transcranial Doppler (TCD) pattern changes in migraine patients in response to rTMS. | Mean flow velocity (cm/s). | Baseline and at month 3 post treatment | 
| Electroencephalography (EEG) pattern change in migraine patients in response to rTMS. | EEG pattern differences based on report. | Baseline and at month 3 post treatment | 
| Serum serotonin level in migraine patients in response to rTMS. | Serum serotonin (ng/ml). | Baseline and at month 3 post treatment | 
| Serum beta-endorphin level changes in migraine patients in response to rTMS. | Serum beta endorphin (ng/ml). | Baseline and at month 3 post treatment | 
| Serum Calcitonin gene related peptide (CGRP) level in migraine patients in response to rTMS. | Serum CGRP (pg/ml). | Baseline and at month 3 post treatment | 
| Satisfaction measures of efficacy, tolerability, safety and expectations of rTMS among the participants. | A 5-point, Likert scale will be used to evaluate satisfaction with rTMS in migraine prevention. | At month 3 post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Protocol, Repetitive Transcranial Magnetic Stimulation, Transcranial Doppler, Neuromodulation, Randomized Controlled Trials, Pain, Migraine prophylaxis, Dorsolateral Prefrontal Cortex