Peripheral Electrical Stimulation for Migraine Prevention

Study Overview
=================
Brief Summary
-----------------
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.

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

Conditions
-----------------
Migraine

Intervention / Treatment
-----------------
* Device: peripheral electrical stimulation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Migraine: Diagnosed as migraine by International Classification of Headache Disorder (ICHD-III) criteria onset before 50 years old 20-65 yrs. 4 or more migraine days per month in average Healthy control: devoid of any systemic or neurological diseases Exclusion Criteria: history of major systemic illness, including uncontrolled hypertension, diabetes, chronic renal insufficiency, autoimmune diseases or malignancies history of neurological disorders which might affect sensation such as previous stroke or peripheral neuropathy pregnancy or lactation epilepsy moderate depressed (BDI>20) using prophylactics for migraine other remote electrical stimulation contraindications, such as open wound, sensory impairment, metal implant other transcranial magnetic stimulation contraindications, such as, high intracranial pressure, cochlear implant, cranial metal implant other magnetic resonance imaging contraindications, such as, pacemaker, stent, metal implant, claustrophobia

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active stimulation<br> | Device: peripheral electrical stimulation<br>* 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.<br>|
| Sham Comparator: Sham stimulation<br> | Device: peripheral electrical stimulation<br>* 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.<br>|
| No Intervention: healthy control<br> | |

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 |