Peripheral Electrical Stimulation for Migraine Prevention

To Investigate the Effects of Peripheral Electrical Stimulation on Cortical Imagining, Electrophysiology and Clinical Profile in Patients With Migraine

Migraine is a common and disabling disease that affects more than 10% of the population worldwide. The prevalence of migraine in Taiwan is around 9.1%. The migraineurs missed 2 workdays due to migraine per year, that is 3.7 million estimated missed workdays in total and an estimated cost of 4.6 billion New Taiwan dollars. In addition, some migraineurs have poor response to the medications or suffer from adverse effects, and may further develop medication-overuse headache. Therefore, in recent years, efforts have been made to develop non-medication treatments, and the number of studies using neuromodulation as an intervention has increased dramatically. Among them, peripheral electrical stimulation has long been a routine treatment for pain in the clinic, and research has also shown its good evidence. In addition, recent studies have shown that peripheral electrical stimulation can also alter the cortical activities. Compared with the proximal brain stimulation, the remote electrical stimulation is safer, more convenient, less expensive and suitable for home use. To date, only one research had focused on the immediate anesthetic effect of remote electrical stimulation whereas the research for migraine prevention is still absent. Therefore, we expect to utilize a more remote electrical stimulation than trigeminal nerve electrical stimulation, which is the commonly used research method nowadays, as an interventional model. In three years, we will recruit 80 migraineurs along with 40 healthy controls and investigate the effects of 8-week home-based remote electrical stimulation on the prevention of migraine and the mechanisms using brain imaging, electrophysiological and biochemical examinations. We also aim to identify the predictors of the responders to remote electrical stimulation. If the effects of remote electrical stimulation are confirmed, as a non-drug neuromodulation management with features of non-invasive, low adverse effects and high accessibility, it will greatly lower the cost of social health care and better improve the quality of life and clinical status of the migraineurs.

Study Overview

• Status: Unknown
• Conditions: Migraine
• Intervention / Treatment: Device: peripheral electrical stimulation

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Migraine:

  1. Diagnosed as migraine by International Classification of Headache Disorder (ICHD-III) criteria
  2. onset before 50 years old
  3. 20-65 yrs.
  4. 4 or more migraine days per month in average

• Healthy control:

  1. devoid of any systemic or neurological diseases

Exclusion Criteria:

1. history of major systemic illness, including uncontrolled hypertension, diabetes, chronic renal insufficiency, autoimmune diseases or malignancies
2. history of neurological disorders which might affect sensation such as previous stroke or peripheral neuropathy
3. pregnancy or lactation
4. epilepsy
5. moderate depressed (BDI>20)
6. using prophylactics for migraine
7. other remote electrical stimulation contraindications, such as open wound, sensory impairment, metal implant
8. other transcranial magnetic stimulation contraindications, such as, high intracranial pressure, cochlear implant, cranial metal implant
9. other magnetic resonance imaging contraindications, such as, pacemaker, stent, metal implant, claustrophobia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Sham stimulation	Device: peripheral electrical stimulation; The subjects will undergo 8-week home-based peripheral electrical simulation on the median nerve. The peripheral electrical simulation will be performed once a day for 30 minutes. The stimulation will be active or sham depend on the group assignment.
Experimental: Active stimulation	Device: peripheral electrical stimulation; The subjects will undergo 8-week home-based peripheral electrical simulation on the median nerve. The peripheral electrical simulation will be performed once a day for 30 minutes. The stimulation will be active or sham depend on the group assignment.
No Intervention: healthy control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in migraine or headache days of a month in average	change in migraine or headache days of a month in average	2 months
responder rate	responder rate (50% pain reduction from baseline)	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in moderate to severe headache days of a month in average		2 months
acute headache medication use		2 months
Beck Depression Inventory		2 months
modified Migraine Disability Scale	This modified Migraine Disability Scale assesses the migraine related disability in the past 1 month. The total score will be compared and the lower score stands for better outcome.	2 months
Patient/Clinical Global Impression of Change	Patient/Clinical Global Impression of Change (PGIC/CGIC) are 7-point scales to assess the improvement by patients themselves and by their clinicians.	2 months
Sensory threshold change after treatment	Using quantitative sensory testing (QST) to evaluate the sensory threshold before and after treatment	2 months
EEG change after treatment (1) Linear analysis of EEG before and after treatment	power spectal density change of EEG before and after treatment	2 months
EEG change after treatment (2) Nonlinear analysis of EEG before and after treatment	functional connectivity change of EEG before and after treatment	2 months
fMRI change after treatment	functional connectivity change of fMRI before and after treatment	2 months
MRI change after treatment	VBM changes of MRI before and after treatment	2 months

Collaborators and Investigators

• Sponsor: Taipei Veterans General Hospital, Taiwan

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2021
• Primary Completion (Anticipated): June 30, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: April 2, 2019
• First Submitted That Met QC Criteria: April 2, 2019
• First Posted (Actual): April 3, 2019

Study Record Updates

• Last Update Posted (Actual): January 29, 2021
• Last Update Submitted That Met QC Criteria: January 26, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: 2019-01-001C

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No