Efficacy and Safety of TMS for the Preemptive Treatment of Migraine With Aura

Study Overview
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Brief Summary
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Assess safety and efficacy of Transcranial Magnetic Stimulation (TMS) for the treatment of migraine with aura The hypothesis is that TMS treatments delivered to the occipital cortex of the brain can stop or interrupt the spreading cortical brain activity that causes or contributes to the migraine headache. Two TMS treatments at an intensity of <1 Tesla for  500 microseconds, approximately 30 seconds apart, may stop the aura and prevent the subsequent headache.

Detailed Description
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In the Lead-in Phase participants will use a Personal Digital Assistant (PDA) to keep an electronic diary of their migraine episodes. During a migraine episode, as well as the time in between headaches, the PDA prompts the participant to answer questions. Each evening, the participant will place the PDA into an electronic telephone cradle, and the information will be transmitted electronically from the PDA to the data management team to assess the frequency of migraine episodes and participant proficiency with the PDA. During this one month period, the participant must experience at least one migraine with aura episode to enter the Treatment Phase. After one month, the participant will return to the clinic with their PDA and will enter the Treatment Phase to be randomized to either the TMS only group or the Sham stimulation only group. Participant will enter information into the PDA for three migraine auras treated or three months, which ever comes first.

Official Title
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Phase III Randomized Double-Blind Parallel Group Sham-Controlled Study Evaluating the Efficacy and Safety of Non-invasive Non-repetitive Transcranial Magnetic Stimulation (TMS) for the Acute Preemptive Treatment of the Aura Phase of Migraine Headache

Conditions
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Migraine With Aura

Intervention / Treatment
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* Device: Active Transcranial Magnetic Stimulation (TMS) Device
* Device: Sham TMS Device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 - 65 years Will comply with requirements of the protocol Have a consistent history of migraine with visual aura of at least one year •>30% of episodes have a visual aura preceding headaches Approximately 90% of the time have moderate or severe headaches following their aura Fulfills the International Classification of Headache Disorders, 2nd Edition(ICHD-II) criteria(for migraine headache with aura after administration of a clinical interview by study personnel Has a history of 1-8 migraine headache episodes with aura per month Can differentiate a migraine headache from other types of headaches Participant is post-menopausal, sterilized, not breastfeeding, her pregnancy test is negative Exclusion Criteria: Women who are pregnant or breastfeeding Routinely experiences any other type of headache that would confound discrimination from migraine headache with aura Have migraine with prolonged aura > 60 minutes Have headaches due to other underlying pathology Have headaches related to head or neck trauma Overuse headache medications: Has an intracranial metallic or Transcranial Magnetic Stimulation (TMS) implant or other metallic implants Has cardiac pacemaker or any other implanted electronic device Has any known history of alcohol abuse, drug dependency, or significant psychiatric illness in the previous 12 months Having any medical condition, including but not limited to: clinically significant renal or hepatic disease; uncontrolled hypertension; clinically significant coronary vascular disease not stable for the past 6 months; personal or family history of seizures or taking medications for seizures or drugs that may lower seizure threshold, cerebral vascular ischemia; infarct; hemorrhage, or other central nervous system disease (e.g., multiple sclerosis, amyotrophic lateral sclerosis); unstable metabolic disease, hypoglycemia or diabetes; malignancy within the past 5 years excluding cutaneous basal cell carcinoma; tuberculosis Has participated in any other investigational study within the previous 30 days. Cannot place the device within 1 cm of the scalp.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Transcranial Magnetic Stimulation (TMS) Device<br>Both arms of participants receive identical looking devices and were instructed use the same treatment protocol. Participants in each group were instructed to treat with the device within one hour of onset of migraine aura. | Device: Active Transcranial Magnetic Stimulation (TMS) Device<br>* Transcranial Magnetic Stimulation Device treatment<br>|
| Sham Comparator: Sham TMS Device<br>Both arms of participants receive identical looking devices and were instructed use the same treatment protocol. Participants in each group were instructed to treat with the device within one hour of onset of migraine aura. | Device: Sham TMS Device<br>* Simulated Sham treatment without TMS delivery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Experiencing no Pain at Two Hours Post-treatment | Number of participants experiencing no pain at two hours post-treatment divided by total number of participants treated. For each treated aura episode during the migraine treatment phase, the subjects rated the pain intensity of their headache as none, mild, moderate or severe at baseline (before application of the study device) at 30 minutes, and at 1, 2, 24, and 48 hours posttreatement. | Two hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Have Symptoms of Nausea | Percentage of participants who have symptoms of nausea two hours post treatment. For each treated aura episode, the subjects rated the severity of photophobia, nausea, and phonophobia as none, mild, moderate, or severe at baseline and recorded the presence or absence of vomiting at baseline (before application of the device) at 30 minutes, and at 1, 2, 24 and 48 hours posttreatment. | two hours post treatment | 
| Percentage of Participants Who Have Symptoms Phonophobia | Percentage of participants who have symptoms of phonophobia two hours post treatment. For each treated aura episode, the subjects rated the severity of photophobia, nausea, and phonophobia as none, mild, moderate, or severe at baseline and recorded the presence or absence of vomiting at baseline (before application of the device) at 30 minutes, and at 1, 2, 24 and 48 hours posttreatment. | 2 hours post treatment | 
| Percentage of Participants Who Have Photophobia | Percentage of participants who have symptoms of photophobia two hours post treatment. For each treated aura episode, the subjects rated the severity of photophobia, nausea, and phonophobia as none, mild, moderate, or severe at baseline and recorded the presence or absence of vomiting at baseline (before application of the device) at 30 minutes, and at 1, 2, 24 and 48 hours posttreatment. | 2 hours post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Migraine with aura, aura, TMS