Investigation and Modulation of the Central Mu-Opioid Mechanism in Migraine (in Vivo)

This study investigates whether unilateral and bilateral non-invasive brain stimulation, given for 20 minutes/once per day for twenty days (M-F) can reduce migraine pain. Fourty patients will receive treatment (20 unilateral treatment, and 20 bilateral treatment), while twenty will receive a "sham" procedure. Another 20 Episodic Migraine patients will be recruited for the observational aim of the study which does not include brain stimulation.

Study Overview

• Status: Recruiting
• Conditions: Chronic Migraine
• Intervention / Treatment: Device: HD-tDCS Active Protocol; Device: HD-tDCS Sham Protocol

Detailed Description

Clinical Trial:

This is a phase 2, single center, three-arm, double-masked, randomized investigation and modulation of the µ-opioid and D2/D3 mechanisms in chronic migraine (in vivo). We will enroll 60 patients with Chronic Migraine divided into 3 Lab/Home-Based groups: 20 for the active unilateral M11-2 HD-tDCS group, 20 for the active bilateral M11-2 HD-tDCS group, and 20 for the sham M11-2 HD-tDCS group. Patients will complete a screening visit, baseline visit with MRI and PET session, 20 days of HD-tDCS brain stimulation treatments, as well as follow-up visits with an MRI and PET session.

Observational Study Arm:

20 additional patients with low frequency EM (<8 attacks/month) patients (that did not undergo neuromodulation) will be recruited for the study. Historical data may be used in place of recruiting new participants. Data from these 20 EM volunteers will be compared to that of CM patients at baseline; however, they will not be part of the clinical trial.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jacqueline Dobson, BA; Phone Number: (734)763-8469; Email: contactHOPE@umich.edu

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
      • Contact: Jacqueline Dobson; Phone Number: 734-763-8469; Email: ContactHOPE@umich.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female, aged 18 to 65 (inclusive)

• Patients must have Episodic migraines that started before the age of 50, and currently experience:

  • Chronic migraine (ICHD-3-beta), headache occurring on 15 days/month for more than six months, which, on at least eight days/month, has the features of a migraine headache.
  • Episodic migraine (low frequency), specifically those with headache occurring less than 8 days/month.
• Willing to limit the introduction of new treatments and medications during the study period.

Exclusion Criteria:

• Significantly greater pain in body sites other than the head

• Active, untreated major concurrent systemic illness other than migraine

  • Medical conditions that can impair health status independent of migraine (including cardiopulmonary disorders, malignancy, uncontrolled endocrine or allergies)
  • Systemic rheumatic disorders (i.e., rheumatoid arthritis, systemic lupus erythematosus, gout, and fibromyalgia);
• History or current evidence of a psychotic disorder (e.g., bipolar disorder, schizophrenia) or severe major depression, as evidenced by Beck Depression score of >30*
• History of neurological disorder (e.g., epilepsy, stroke, neuropathy, neuropathic pain)
• Medication overuse headache (ICHD-3), regular intake for ≥10 days per month of ergotamine, triptans, combination analgesics, or any combination thereof OR ≥15 days per month of simple analgesics (acetaminophen, aspirin, NSAID), for more than 3 months
• Current use of opioid or dopaminergic drugs (or use within the last 3 months) or substance abuse (self-reported)
• Drug test positive for opioid or recreational drug (e.g., cannabis) at the time of the PET scan visits
• Allergic response to study radiotracers or chemically related drugs
• Excluded by MRI Center or PET Center safety screening checklist (as administered by study staff)
• Pregnant or lactating (negative urine pregnancy test must be available before any PET procedures are initiated)
• Prior use of tDCS

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active Unilateral Treatment; Chronic migraine patients will be randomized (Taves method) to receive UNILATERAL high-definition transcranial direct current stimulation (HD-tDCS*) as 20 minute sessions, once daily for 20 days (M-F for 4 weeks).	Device: HD-tDCS Active Protocol; non-invasive brain stimulation (active protocol)
Active Comparator: Active Bilateral Treatment; Chronic migraine patients will be randomized (Taves method) to receive BILATERAL high-definition transcranial direct current stimulation (HD-tDCS*) as 20 minute sessions, once daily for 20 days (M-F for 4 weeks).	Device: HD-tDCS Active Protocol; non-invasive brain stimulation (active protocol)
Sham Comparator: Sham Treatment; Chronic migraine patients will be randomized (Taves method) to receive SHAM high-definition transcranial direct current stimulation (HD-tDCS*) as 30-second administrations at the beginning and end of each 20 minute session, once daily for 20 days (M-F for 4 weeks).	Device: HD-tDCS Sham Protocol; non-invasive brain stimulation (sham protocol)
No Intervention: No Treatment; Episodic Migraine Patients will not receive study treatment. These patients will complete observational study components (Screening visit, baseline visit, MRI and PET scan only).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in moderate to severe headache days over 1 month follow-up	Headache Day: day with a headache that causes moderate or severe pain (at its peak, defined as NRS ≥ 4) that lasts at least 4 hours, OR day with a headache that is treated by an acute headache medication.	baseline to 1 month follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in headache days over 1-month follow-up	Day with a headache that lasts at least 2 hours, OR day with a headache that is treated by an acute headache medication.	baseline to 1 month follow-up
Responder rate over 1-month follow-up	50% percent reduction (from baseline to post tDCS) in the number of moderate or severe headache days.	baseline to 1 month follow-up
Changes from baseline in medication use days over 1-month follow-up	- Medication use is defined as a day when the patient reports intake of medication for the acute treatment of headache	baseline to 1 month follow-up
Intensity of headache over 1-month follow-up	Each headache day is rated in terms of maximum intensity on a 0 to 10 NRS scale and averaged headache intensity will be used.	baseline to 1 month follow-up

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Alexandre DaSilva, DDS, DMedSc, University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2023
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: February 13, 2023
• First Submitted That Met QC Criteria: March 13, 2023
• First Posted (Actual): March 15, 2023

Study Record Updates

• Last Update Posted (Actual): February 25, 2026
• Last Update Submitted That Met QC Criteria: February 23, 2026
• Last Verified: February 1, 2026

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: HUM00213295; R01NS094413 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes