A Study of Home-Delivered Neurostimulation for Migraine

Study Overview
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Brief Summary
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There is a need for better preventive and abortive therapies for migraine. Previous research has indicated that non-invasive neurostimulation may have prophylactic effects on migraine and improve symptoms and functional outcomes in migraineurs. One such method is a non-invasive transcranial direct current stimulation (tDCS). This double-blind randomized sham-controlled two-parallel-arm study aims to evaluate efficacy and safety of tDCS self-delivered in daily 20-minute applications for 2 months (60 days) by adult migraine patients at home for migraine prevention and migraine symptom management, as compared to sham tDCS application; and to evaluate patients' satisfaction with the procedure.

Detailed Description
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This study will employ a double-blind randomized sham-controlled two-parallel-arm design and involve 60 adults with migraine. For each participant, the study will involve 3 study visits and last about 90 days (30 days of the baseline followed by 60 days of the tDCS/sham study intervention). A post-study safety monitoring will continue bi-weekly by phone for 30 days after the last tDCS/sham application. At Visit 1, patients will provide written informed consent and undergo screening for the eligibility. This will be followed by 30 days of baseline at home during which patients will keep daily records (Daily Diaries) of migraine occurrence and provide answers to a set of symptom-related questionnaires. Patients with 4 or more migraine days per month who fully meet the study eligibility criteria at the end of the baseline period will be randomized in double-blind manner into two groups: Group 1 will be randomized to receive active tDCS in daily 20-minute applications for 60 days; Group 2 will be randomized to receive sham tDCS in daily 20-minute applications for 60 days, self-applied at home. Following randomization, patients will continue keeping the Daily Diaries and Visit #2 will be held either in the patient's home or in the research facility, based on the patient's preference. tDCS device will be deployed to the patient and instructions on tDCS use will be provided. The first tDCS/sham self-application by the patient will be done at Visit 2. Daily tDCS/sham self-application by the patient at home and records in the form of Daily Diaries will continue for the rest of the 60-day period. Study staff will be in regular remote contact with the patient via phone and/or HIPAA-compliant videoconferencing. Upon conclusion of the intervention, Visit 3 will be held either in the patient's home or in the research facility, based on the patient's preference. tDCS device will be collected from the patient. Safety monitoring will continue bi-weekly by phone for 30 days after the last tDCS/sham application. Outcome assessment will be carried out at the end of the baseline, and at Day 30 (the secondary time-point) and Day 60 (the primary time-point) of the tDCS/sham intervention.

Official Title
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A Randomized Sham-Controlled Study of Home-Delivered Non-Invasive Neurostimulation for Migraine

Conditions
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Migraine Disorders

Intervention / Treatment
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* Device: non-invasive transcranial direct current stimulation (tDCS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 - 65 years; Has episodic or chronic migraine with or without aura, diagnosed according to the International Classification of Headache Disorders 3rd edition (ICHD-3) criteria, for at least the past 12 months; Migraine occurring on 4 or more days per month, as documented through the 30-day baseline; No change in prophylactic therapy in 3 months preceding the baseline; If on antidepressant, blood pressure or epilepsy medication for reason other than migraine, the medication regimen is stable for at least 3 months preceding the baseline; Able to follow instructions in English; Understand the informed consent process and provide consent to participate in the study. Exclusion Criteria: History of severe head trauma, brain surgery, implants in the head or neck; history of seizures; Skin disorder or skin defects which compromise the integrity or sensitivity of the skin at or near locations where tDCS will be applied; Not able to prepare and operate the tDCS device after being instructed in tDCS use; Not able to respond to questionnaires and rating scales; Concurrent use of another neurostimulation device (such as spinal cord stimulator cardiostimulator, deep brain stimulator, vagus nerve, transcranial magnetic, or supraorbital transcutaneous electric nerve stimulators); Concurrent use of Botox or calcitonin gene-related peptide (CGRP) monoclonal antibodies treatments; Unstable acute medical condition; Any serious, malignant or non-malignant, acute or chronic medical condition or active psychiatric illness that, in the Investigator's opinion, could compromise patient safety, limit the patient's ability to complete the study, and/or compromise the objectives of the study; Used any investigational drug, biologic, or device within 30 days prior to screening, or 5 half-lives, whichever is longer; Taking opioid analgesics or barbiturates on more than 2 days a week; Taking medications acting as antagonist on the N-methyl-D-aspartate (NMDA) receptor.

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: Active tDCS<br>Twenty minutes of direct current at intensity of 1.5 milliamperes (mA). | Device: non-invasive transcranial direct current stimulation (tDCS)<br>* Active tDCS: transcranial direct current stimulation at intensity 1.5mA for 20 minutes per day on 60 consecutive days, over the area of the dorsolateral prefrontal cortex, using sponge saline-premoisturized electrodes of size 5x5cm, the anode on the left, the cathode on the right. Sham tDCS: transcranial direct current stimulation at intensity 1.5mA for 30seconds followed by 0 mA current for remaining time of the 20-minute intervention per day on 60 consecutive days, over the area of the dorsolateral prefrontal cortex, using sponge saline-premoisturized electrodes of size 5x5cm, the anode on the left, the cathode on the right.<br>|
| Sham Comparator: Sham tDCS<br>Thirty seconds of direct current at 1.5 mA, followed by 0 mA for the remaining time of the 20-minute stimulation period. | Device: non-invasive transcranial direct current stimulation (tDCS)<br>* Active tDCS: transcranial direct current stimulation at intensity 1.5mA for 20 minutes per day on 60 consecutive days, over the area of the dorsolateral prefrontal cortex, using sponge saline-premoisturized electrodes of size 5x5cm, the anode on the left, the cathode on the right. Sham tDCS: transcranial direct current stimulation at intensity 1.5mA for 30seconds followed by 0 mA current for remaining time of the 20-minute intervention per day on 60 consecutive days, over the area of the dorsolateral prefrontal cortex, using sponge saline-premoisturized electrodes of size 5x5cm, the anode on the left, the cathode on the right.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Migraine Days Per Month | A migraine day is defined as any calendar day on which the patient had onset, continuation, or recurrence of a migraine as recorded in the diary. A migraine is defined as a migraine (with or without aura) lasting at least 30 minutes. Any calendar day on which acute migraine medication is used is counted as a migraine day. | Baseline, Day 30 of the intervention (secondary time point), Day 60 of the intervention (primary time point); | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Responders | determined as a percentage of patients having at least 50% reduction of monthly migraine days between the one-month baseline and post-intervention, in each of the two study groups | Day 60 of the intervention | 
| Migraine Attack Frequency | Median change in number of attacks per 30-day period, determined from the patients' diaries | Baseline, Day 30 of the intervention, Day 60 of the intervention | 
| Acute Medication Use | Acute antimigraine drug use per month determined from the patient's diaries. Median change in number of days on which an acute medication was used. | Baseline, Day 30 of the intervention, Day 60 of the intervention | 
| Change in Headache Attack Intensity Median Change in NRS From Headache Days in a 30 Day Period | Determined from the 11-point [0-10] Pain Numerical Rating Scale (Pain NRS) on migraine days in the patients' diaries. Higher ratings on the Pain NRS reflect higher intensity of pain. | Baseline, Day 30 of the intervention, Day 60 of the intervention; | 
| Change in Quality of Life: The Migraine Specific Quality of Life Questionnaire (MSQ) | Determined from ratings on the migraine-specific MSQ questionnaire. The questionnaire consists of 14 items, each rated on a scale 1-6, with the total score ranging between 14 and 84. Higher scores reflect poorer quality of life. | Baseline, Day 30 of the intervention, Day 60 of the intervention; | 
| Change in Depressive Symptoms | Determined from the Hamilton Depression Scale (HamD) that consists of 21 items with numerically rated responses ranging 0-2 or 0-4. Higher Ham-D score reflects more severe depression. | Baseline, Day 30 of the intervention, Day 60 of the intervention; | 
| Tolerability of the Study Intervention: Number of Side Effects and Adverse Events | Determined as number of side effects and adverse events related, probably related or possibly related to the study intevention | from Day 1 of the study intervention to the end of the safety follow-up thirty days after the last tDCS application | 
| Patient's Satisfaction: 8-item tDCS User Survey | Patient's satisfaction with the study intervention determined from the 8-item tDCS User Survey at the end of the intervention. Each item of the Survey is a brief statement and a respondent indicates if s/he Strongly Agree, Agree, Neither Agree or Disagree, Disagree or Strongly Disagree with the statement. Higher number of Agree/Strongly Agree ratings reflects higher satisfaction with the tDCS procedure. | Day 60 of the intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Migraine;, transcranial direct current stimulation (tDCS), tDCS-Telehealth intervention