A Study of Home-Delivered Neurostimulation for Migraine

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.

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.