Migraine Disorders
Conditions
Keywords
Migraine;, transcranial direct current stimulation (tDCS), tDCS-Telehealth intervention
Brief summary
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
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.
Interventions
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.
Sponsors
New York Headache Center
MJHS Institute for Innovation in Palliative Care
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Migraine Days Per Month | Baseline, Day 30 of the intervention (secondary time point), Day 60 of the intervention (primary time point); | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Migraine Attack Frequency | Baseline, Day 30 of the intervention, Day 60 of the intervention | Median change in number of attacks per 30-day period, determined from the patients' diaries |
| Acute Medication Use | Baseline, Day 30 of the intervention, Day 60 of the intervention | 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. |
| Change in Headache Attack Intensity Median Change in NRS From Headache Days in a 30 Day Period | Baseline, Day 30 of the intervention, Day 60 of the intervention; | 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. |
| Percentage of Responders | Day 60 of the intervention | 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 |
| Change in Depressive Symptoms | Baseline, Day 30 of the intervention, Day 60 of the intervention; | 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. |
| Tolerability of the Study Intervention: Number of Side Effects and Adverse Events | from Day 1 of the study intervention to the end of the safety follow-up thirty days after the last tDCS application | Determined as number of side effects and adverse events related, probably related or possibly related to the study intevention |
| Patient's Satisfaction: 8-item tDCS User Survey | Day 60 of the intervention | 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. |
| Change in Quality of Life: The Migraine Specific Quality of Life Questionnaire (MSQ) | Baseline, Day 30 of the intervention, Day 60 of the intervention; | 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. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at the New York Headache Center, New York City, NY, USA, between 3/12/2019 and 3/5/2020.
Pre-assignment details
Thirty six patients have been identified. Six declined to participate, 14 did not meet the Inclusion/Exclusion criteria. Twenty two proceeded with the study, were randomized and received the study intervention. The first of the twenty-two patients entered the study on 4/22/19; the last patient out completed the study intervention on 4/10/2020, with the last study visit on 4/13/2020 and the last phone follow-up on 5/12/2020.
Participants by arm
| Arm | Count |
|---|---|
| Active tDCS The active tDCS will involve 20-minutes of direct current at intensity of 1.5 milliamperes (mA).
non-invasive transcranial direct current stimulation (tDCS): Non-invasive remotely supervised transcranial direct current stimulation at intensity 1.5mA or sham applied by participants at home 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. | 11 |
| Sham tDCS Sham will include 30 seconds of stimulation at 1.5 mA, followed by 0 mA for the remaining time.
non-invasive transcranial direct current stimulation (tDCS): Non-invasive remotely supervised transcranial direct current stimulation at intensity 1.5mA or sham applied by participants at home 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. | 11 |
| Total | 22 |
Baseline characteristics
| Characteristic | Active tDCS | Sham tDCS | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 11 Participants | 22 Participants |
| Migraine days per month | 25 migraine days per month | 17 migraine days per month | 23 migraine days per month |
| Race/Ethnicity, Customized African American | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized White, Non-Hispanic | 10 Participants | 5 Participants | 15 Participants |
| Sex: Female, Male Female | 7 Participants | 10 Participants | 17 Participants |
| Sex: Female, Male Male | 4 Participants | 1 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 11 |
| other Total, other adverse events | 1 / 11 | 1 / 11 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 |
Outcome results
Primary
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.
Time frame: Baseline, Day 30 of the intervention (secondary time point), Day 60 of the intervention (primary time point);
Population: Participants who met the Inclusion/Exclusion criteria for the study.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Active tDCS | Migraine Days Per Month | Migraine days per month at day 60 of the intervention (primary outcome) (primary) | -8 migraine days per month |
| Active tDCS | Migraine Days Per Month | Migraine days per month at day 30 of the intervention (secondary outcome) | -3 migraine days per month |
| Sham tDCS | Migraine Days Per Month | Migraine days per month at day 60 of the intervention (primary outcome) (primary) | -4 migraine days per month |
| Sham tDCS | Migraine Days Per Month | Migraine days per month at day 30 of the intervention (secondary outcome) | -3 migraine days per month |
Secondary
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.
Time frame: Baseline, Day 30 of the intervention, Day 60 of the intervention
Population: Participants who met the Inclusion/Exclusion criteria of the study
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Active tDCS | Acute Medication Use | Acute antimigraine drug use - day 60 of the intervention | -2 Days/month |
| Active tDCS | Acute Medication Use | Acute antimigraine drug use - day 30 of the intervention | -1 Days/month |
| Sham tDCS | Acute Medication Use | Acute antimigraine drug use - day 30 of the intervention | -1 Days/month |
| Sham tDCS | Acute Medication Use | Acute antimigraine drug use - day 60 of the intervention | -2 Days/month |
Secondary
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.
Time frame: Baseline, Day 30 of the intervention, Day 60 of the intervention;
Population: Participants who met the Inclusion/Exclusion criteria of the study
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Active tDCS | Change in Depressive Symptoms | Change in depressive symptoms - day 30 of the intervention | -4 Score on a scale |
| Active tDCS | Change in Depressive Symptoms | Change in depressive symptoms - day 60 of the intervention | -5 Score on a scale |
| Sham tDCS | Change in Depressive Symptoms | Change in depressive symptoms - day 30 of the intervention | -2 Score on a scale |
| Sham tDCS | Change in Depressive Symptoms | Change in depressive symptoms - day 60 of the intervention | -3 Score on a scale |
Secondary
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.
Time frame: Baseline, Day 30 of the intervention, Day 60 of the intervention;
Population: Participants who met the Inclusion/Exclusion criteria of the study.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Active tDCS | Change in Headache Attack Intensity Median Change in NRS From Headache Days in a 30 Day Period | Change in headache attack intensity - day 30 of the intervention | 0 Score on a scale |
| Active tDCS | Change in Headache Attack Intensity Median Change in NRS From Headache Days in a 30 Day Period | Change in headache attack intensity - day 60 of the intervention | -1 Score on a scale |
| Sham tDCS | Change in Headache Attack Intensity Median Change in NRS From Headache Days in a 30 Day Period | Change in headache attack intensity - day 30 of the intervention | -1 Score on a scale |
| Sham tDCS | Change in Headache Attack Intensity Median Change in NRS From Headache Days in a 30 Day Period | Change in headache attack intensity - day 60 of the intervention | -1 Score on a scale |
Secondary
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.
Time frame: Baseline, Day 30 of the intervention, Day 60 of the intervention;
Population: Participants who met the Inclusion/Exclusion criteria of the study.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Active tDCS | Change in Quality of Life: The Migraine Specific Quality of Life Questionnaire (MSQ) | Change in quality of life - day 30 of the intervention | -11 Score on a scale |
| Active tDCS | Change in Quality of Life: The Migraine Specific Quality of Life Questionnaire (MSQ) | Change in quality of life - day 60 of the intervention | -12 Score on a scale |
| Sham tDCS | Change in Quality of Life: The Migraine Specific Quality of Life Questionnaire (MSQ) | Change in quality of life - day 30 of the intervention | -7 Score on a scale |
| Sham tDCS | Change in Quality of Life: The Migraine Specific Quality of Life Questionnaire (MSQ) | Change in quality of life - day 60 of the intervention | -8 Score on a scale |
Secondary
Migraine Attack Frequency
Median change in number of attacks per 30-day period, determined from the patients' diaries
Time frame: Baseline, Day 30 of the intervention, Day 60 of the intervention
Population: Participants who met the Inclusion/Exclusion criteria of the study.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Active tDCS | Migraine Attack Frequency | Migraine attack frequency at day 60 of the interrvention | -1 migraine attacks per month |
| Active tDCS | Migraine Attack Frequency | Migraine attack frequency at day 30 of the intervention | 1 migraine attacks per month |
| Sham tDCS | Migraine Attack Frequency | Migraine attack frequency at day 60 of the interrvention | -2 migraine attacks per month |
| Sham tDCS | Migraine Attack Frequency | Migraine attack frequency at day 30 of the intervention | 0 migraine attacks per month |
Secondary
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.
Time frame: Day 60 of the intervention
Population: Participants who met the Inclusion/Exclusion criteria of the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active tDCS | Patient's Satisfaction: 8-item tDCS User Survey | 41 number of Agree/Strongly Agree ratings |
| Sham tDCS | Patient's Satisfaction: 8-item tDCS User Survey | 57 number of Agree/Strongly Agree ratings |
Secondary
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
Time frame: Day 60 of the intervention
Population: Participants who met the Inclusion/Exclusion criteria of the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active tDCS | Percentage of Responders | 18.18 percentage of participants |
| Sham tDCS | Percentage of Responders | 36.36 percentage of participants |
Secondary
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
Time frame: from Day 1 of the study intervention to the end of the safety follow-up thirty days after the last tDCS application
Population: Participants who met the Inclusion/Exclusion criteria of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active tDCS | Tolerability of the Study Intervention: Number of Side Effects and Adverse Events | 3 events |
| Sham tDCS | Tolerability of the Study Intervention: Number of Side Effects and Adverse Events | 0 events |