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

NCT02964741 | Terminated Results FDA Device

• 2 other identifiers: HUM00107286R01NS094413
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

This study investigates whether non-invasive brain stimulation, given for 20 minutes/once per day for ten days (M-F) can reduce migraine pain. Thirty patients will receive this treatment, while thirty will receive a "sham" procedure. Up to thirty healthy volunteers will be asked to undergo baseline assessments only (imaging, but no brain stimulation). Healthy volunteer data may be used from a prior study (NINDS-K23062946 project \[IRBMED #HUM00027383; Dr. Alexandre DaSilva, Principal Investigator\]).

Conditions

Migraine

Keywords

Episodic Migraine; Headache; Opioid

Outcome Measures

Primary Outcomes (2)

• Days With Moderate-to-severe Headache

  Moderate to severe headache is defined by the pain over 3 in an Numeric Rating Scale (NRS) ranging from 0 to 10 between end of treatment and one month follow-up.

  End of treatment - over 1 month follow-up

• Responder Rate

  Number of participants who showed a 50% reduction of days with moderate-to-severe headache compared to baseline.

  End of treatment - over 1 month follow-up

Secondary Outcomes (5)

• Change in Pain Intensity Level Measured by the Visual Analog Scale in Migraineurs (Active or Sham)

  Approximately 45 days (Screening Visit [Original Baseline] to Follow Up #2 [28-days post-HD-tDCS treatment])

• Moderate to Severe Headache

  End of treatment - over 1 month follow-up

• Use of Rescue Medication

  End of treatment - over 1 month follow-up

• Change in Mu-opioid Receptor Non-displaceable Binding Potential (BPND) in the Brains of Migraineurs During Sustained Thermal Pain Threshold Stress Challenge Subsequent to Treatment by HD-tDCS (Active or Sham).

  Time between PET #1 and PET #2 is typically 21 days (minimum 17 days; maximum 42 days).

• Change in Mu-opioid Receptor Non-displaceable Binding Potential (BPND) in the Brains of Migraineurs at Rest Subsequent to Treatment by HD-tDCS (Active or Sham).

  Time between PET #1 and PET #2 is typically 21 days (minimum 17 days; maximum 42 days).

Study Arms (3)

Migraine Patients Active Group

ACTIVE COMPARATOR

Episodic migraine patients will be randomized (Taves method) to receive high-definition transcranial direct current stimulation (HD-tDCS\*) as 20 minute sessions, once daily for 10 days (M-F for 2 weeks). \*Active Comparator

Device: Active Comparator

Migraine Patients Sham Group

SHAM COMPARATOR

Episodic migraine patients will be randomized (Taves method) to receive 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 10 days (M-F for 2 weeks). \*Sham Comparator

Device: Sham Comparator

Healthy Control Group

NO INTERVENTION

Healthy Volunteers will be asked to undergo baseline assessments only (including imaging, but no brain stimulation). Healthy volunteer data (n \</= 10) may be used from a prior study (NINDS-K23062946 project \[IRBMED #HUM00027383; Dr. Alexandre DaSilva, Principal Investigator\]). Consent to use data for a future study was obtained in the informed consent document at the time of participation.

Interventions

Active Comparator DEVICE

non-invasive brain stimulation (active protocol)

Also known as: HD-tDCS (active protocol)

Migraine Patients Active Group

Sham Comparator DEVICE

non-invasive brain stimulation (sham protocol)

Also known as: HD-tDCS (sham protocol)

Migraine Patients Sham Group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Episodic migraine (ICHD-3-beta) for at least 6 months, with at least one attack per month and less than 15 attacks per month
• No intake of opiate medication for the past six months
• No overuse of analgesic medication, defined as regular intake on ≥15 days per month for more than 3 months
• Willing to limit the introduction of new treatments for headache management

You may not qualify if:

• Presence of any other systemic or chronic pain disorder
• History or current evidence of a psychotic disorder (e.g. schizophrenia) or substance abuse; bipolar or severe major depression, as evidenced by Beck Depression score of ≥ 30
• History of neurological disorder (e.g. epilepsy, stroke, neuropathy, neuropathic pain)
• Prior use of tDCS
• Current use of opioid pain medications

Sponsors & Collaborators

• University of Michigan: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

University of Michigan School of Dentistry

Ann Arbor, Michigan, 48109-5720, United States

Location

Related Publications (2)

• Lim M, Kim DJ, Nascimento TD, DaSilva AF. High-definition tDCS over primary motor cortex modulates brain signal variability and functional connectivity in episodic migraine. Clin Neurophysiol. 2024 May;161:101-111. doi: 10.1016/j.clinph.2024.02.012. Epub 2024 Feb 15.

  PMID: 38460220 DERIVED

• DaSilva AF, Kim DJ, Lim M, Nascimento TD, Scott PJH, Smith YR, Koeppe RA, Zubieta JK, Kaciroti N. Effect of High-Definition Transcranial Direct Current Stimulation on Headache Severity and Central micro-Opioid Receptor Availability in Episodic Migraine. J Pain Res. 2023 Jul 21;16:2509-2523. doi: 10.2147/JPR.S407738. eCollection 2023.

  PMID: 37497372 DERIVED

MeSH Terms

Conditions

Migraine Disorders; Headache

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Jacqueline Dobson
• Organization: University of Michigan

contacthope@umich.edu

734-763-8469

Study Officials

• Alexandre F DaSilva, DDS, DMedSc

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Biologic and Materials Science, School of Dentistry and Research Assistant Professor, Center for Human Growth & Development

Study Record Dates

• First Submitted: October 7, 2016
• First Posted: November 16, 2016
• Study Start: February 22, 2017
• Primary Completion: June 1, 2021
• Study Completion: August 1, 2021
• Last Updated: August 26, 2022
• Results First Posted: July 12, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)