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

Primary Purpose

Chronic Migraine

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
HD-tDCS Active Protocol
HD-tDCS Sham Protocol
Sponsored by
University of Michigan
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Migraine

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of MichiganRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Active Comparator

Sham Comparator

No Intervention

Arm Label

Active Unilateral Treatment

Active Bilateral Treatment

Sham Treatment

No Treatment

Arm Description

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).

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).

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).

Episodic Migraine Patients will not receive study treatment. These patients will complete observational study components (Screening visit, baseline visit, MRI and PET scan only).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Responder rate over 1-month follow-up
50% percent reduction (from baseline to post tDCS) in the number of moderate or severe headache days.
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
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.

Full Information

First Posted
February 13, 2023
Last Updated
March 13, 2023
Sponsor
University of Michigan
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
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1. Study Identification

Unique Protocol Identification Number
NCT05769348
Brief Title
Investigation and Modulation of the Central Mu-Opioid Mechanism in Migraine (in Vivo)
Official Title
Investigation and Modulation of the Central Mu-Opioid Mechanism in Migraine (in Vivo)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 26, 2023 (Actual)
Primary Completion Date
December 30, 2025 (Anticipated)
Study Completion Date
December 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Michigan
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Migraine

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Masking Description
Patients will not know if they are receiving active or sham treatment
Allocation
Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Active Unilateral Treatment
Arm Type
Active Comparator
Arm Description
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).
Arm Title
Active Bilateral Treatment
Arm Type
Active Comparator
Arm Description
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).
Arm Title
Sham Treatment
Arm Type
Sham Comparator
Arm Description
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).
Arm Title
No Treatment
Arm Type
No Intervention
Arm Description
Episodic Migraine Patients will not receive study treatment. These patients will complete observational study components (Screening visit, baseline visit, MRI and PET scan only).
Intervention Type
Device
Intervention Name(s)
HD-tDCS Active Protocol
Intervention Description
non-invasive brain stimulation (active protocol)
Intervention Type
Device
Intervention Name(s)
HD-tDCS Sham Protocol
Intervention Description
non-invasive brain stimulation (sham protocol)
Primary Outcome Measure Information:
Title
Change from baseline in moderate to severe headache days over 1 month follow-up
Description
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.
Time Frame
baseline to 1 month follow-up
Secondary Outcome Measure Information:
Title
Change from baseline in headache days over 1-month follow-up
Description
Day with a headache that lasts at least 2 hours, OR day with a headache that is treated by an acute headache medication.
Time Frame
baseline to 1 month follow-up
Title
Responder rate over 1-month follow-up
Description
50% percent reduction (from baseline to post tDCS) in the number of moderate or severe headache days.
Time Frame
baseline to 1 month follow-up
Title
Changes from baseline in medication use days over 1-month follow-up
Description
- Medication use is defined as a day when the patient reports intake of medication for the acute treatment of headache
Time Frame
baseline to 1 month follow-up
Title
Intensity of headache over 1-month follow-up
Description
Each headache day is rated in terms of maximum intensity on a 0 to 10 NRS scale and averaged headache intensity will be used.
Time Frame
baseline to 1 month follow-up

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jacqueline Dobson, BA
Phone
(734)763-8469
Email
contactHOPE@umich.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alexandre DaSilva, DDS, DMedSc
Organizational Affiliation
University of Michigan
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jacqueline Dobson
Phone
734-763-8469
Email
ContactHOPE@umich.edu

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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