A Phase III Trial of e-TNS for the Acute Treatment of Migraine

Study Overview
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Brief Summary
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The main objective of this study is to have Phase III evidences of the efficacy of the Cefaly® Abortive Program device used at home for 2 hours to treat a migraine attack. This randomized, double-blind, sham-controlled trial will study the abortive treatment of migraine using the Cefaly® Abortive Program device.

Detailed Description
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The main objective of this study is to have Phase III evidences of the efficacy of the Cefaly® Abortive Program device used at home for 2 hours to treat a migraine attack, as triptans are generally used. That is to say having randomized, double-blind, sham-controlled data of the efficacy and safety of the Cefaly® Abortive Program device in the abortive treatment of acute migraine as measured by 2-hour pain freedom, pain relief and migraine-associated symptoms freedom, plus evolution of these measurements for 24 hours after the beginning of the treatment session.

Official Title
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A Phase III Randomized, Double-blind, Sham-controlled Trial of e-TNS for the Acute Treatment of Migraine (The TEAM Study)

Conditions
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Migraine

Intervention / Treatment
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* Device: Verum Cefaly® Abortive Program device
* Device: Sham Cefaly® Abortive Program device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age from 18 to 65 on the day of signing the informed consent form ≥ 1-year history of migraine with or without aura according to the diagnostic criteria listed in International Classification of Headache Disorders (ICHD)-3 beta (2013) section 1, migraine, with the exception of aura without headache, hemiplegic migraine and brainstem aura migraine Migraine onset before the age of 50 Having between 2 and 8 moderate or severe migraine attacks (Grade 2 or 3) per month in each of the two months prior to screening Patient understands the study procedures, alternative treatments available, and voluntarily agrees to participate in the study by giving written informed consent Patient is able to read and understand the written information (instruction sheet, paper diary and Adverse Events reporting form) Exclusion Criteria: Patient has difficulty distinguishing his/her migraine attacks from tension-type headaches Patient has more than 15 headache days per month Patient having received supraorbital nerve blocks in the prior 4 months Patient having received Botox treatment in the prior 4 months Modification of a migraine prophylaxis treatment in the previous 3 months Diagnosis of other primary headache disorders, except rare (< 4) tension-type headaches per month Diagnosis of secondary headache disorders including Medication Overuse Headache (MOH) Patient abusing opioids or user of recreational or illicit drugs or having had a recent history (within the last year) of drug or alcohol abuse or dependence Implanted metallic or electronic device in the head Cardiac pacemaker or implanted or wearable defibrillator Patient having had a previous experience with the Cefaly® device Migraine Aura without headache Patient is currently participating or has participated in a study with an investigational compound or device in the last 30 days before the screening visit (Visit 1) Patient not having the ability to use appropriately the device and/or to perform himself/herself or bear the first 20-minute stimulation session during the training test session at the study site

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Verum<br>2-hour external trigeminal nerve stimulation with the Verum Cefaly® Abortive Program device, as abortive treatment of an early stage migraine attack | Device: Verum Cefaly® Abortive Program device<br>* The Cefaly® Abortive Program device is an external cranial neurostimulator designed for supraorbital neurostimulation, also known as external Trigeminal Nerve Stimulation (e-TNS). The Verum Cefaly® Abortive Program device will deliver verum external trigeminal nerve stimulation.<br>|
| Sham Comparator: Sham<br>2-hour external trigeminal nerve stimulation with the Sham Cefaly® Abortive Program device, as abortive treatment of an early stage migraine attack | Device: Sham Cefaly® Abortive Program device<br>* The Cefaly® Abortive Program device is an external cranial neurostimulator designed for supraorbital neurostimulation, also known as external Trigeminal Nerve Stimulation (e-TNS). The Sham Cefaly® Abortive Program device will deliver sham external trigeminal nerve stimulation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Freedom at 2 Hours | The percentage of patients having a reduction of a moderate or severe migraine headache (Grade 2 or 3) at baseline to no headache (Grade 0) at 2 hours after the beginning of the e-TNS session. | 2 hours | 
| Most Bothersome Migraine-associated Symptom Freedom at 2 Hours | The percentage of patients with absence, at 2 hours after the beginning of the e-TNS session, of the most bothersome migraine-associated symptom identified at baseline. | 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Relief at 2 Hours | The percentage of patients having a reduction of a moderate or severe migraine headache (Grade 2 or 3) at baseline to a mild headache or to no headache (Grade 1 or 0) at 2 hours after the beginning of the e-TNS session. | 2 hours | 
| Percentage of Patients With Absence of Photophobia, Phonophobia, Nausea, Vomiting at 2 Hours | The percentage of patients with absence of photophobia, phonophobia, nausea, vomiting at 2 hours after the beginning of the e-TNS session. | 2 hours | 
| Use of Rescue Medication Between 2 and 24 Hours | The percentage of patients who took anti-migraine rescue medication between 2 and 24 hours after the beginning of the e-TNS session. | 2-24 hours | 
| Sustained Pain Freedom at 24 Hours | The percentage of patients having no headache (Grade 0) at 2 hours, with no use of anti-migraine rescue medication and no relapse of headache pain within the 24 hours after the beginning of the e-TNS session. | 24 hours | 
| Sustained Pain Relief at 24 Hours | The percentage of patients having mild or no headache (Grade 1 or 0) at 2 hours, with no use of anti-migraine rescue medication and no relapse of headache pain within the 24 hours after the beginning of the e-TNS session. | 2-24 hours |