We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

This study is currently recruiting participants.
Verified November 2016 by Alexandre DaSilva, DDS, MS, University of Michigan
Sponsor:
ClinicalTrials.gov Identifier:
NCT02964741
First Posted: November 16, 2016
Last Update Posted: March 30, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Alexandre DaSilva, DDS, MS, University of Michigan
  Purpose
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]).

Condition Intervention
Migraine Device: Active Comparator Device: Sham Comparator

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Investigation and Modulation of the Mu-Opioid Mechanisms in Migraine (in Vivo)

Resource links provided by NLM:


Further study details as provided by Alexandre DaSilva, DDS, MS, University of Michigan:

Primary Outcome Measures:
  • Change in pain intensity level measured by the Visual Analog Scale in migraineurs (active or sham) [ Time Frame: Approximately 45 days (Screening Visit [Original Baseline] to Follow Up #2 [28-days post-HD-tDCS treatment]) ]
    Visual Analog Scale measures pain on a 0 to 10 scale, where 0 is "no pain" and 10 is "worst possible pain"


Secondary Outcome Measures:
  • 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 Frame: Time between PET #1 and PET #2 is typically 21 days (minimum 17 days; maximum 42 days). ]

    Mu-opioid receptor BPND at PET #2 will be subtracted from mu-opioid receptor BPND at PET #1.

    PET #1 occurs during the week before HD-tDCS treatment begins. PET #2 occurs during the week after the final HD-tDCS treatment is completed.


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

    Mu-opioid receptor BPND at PET #2 will be subtracted from mu-opioid receptor BPND at PET #1.

    PET #1 occurs during the week before HD-tDCS treatment begins. PET #2 occurs during the week after the final HD-tDCS treatment is completed.



Estimated Enrollment: 90
Actual Study Start Date: February 22, 2017
Estimated Study Completion Date: June 2020
Estimated Primary Completion Date: April 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Migraine Patients Active Group

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
non-invasive brain stimulation (active protocol)
Other Name: HD-tDCS (active protocol)
Sham Comparator: Migraine Patients Sham Group

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
non-invasive brain stimulation (sham protocol)
Other Name: HD-tDCS (sham protocol)
No Intervention: Healthy Control Group

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.


Detailed Description:

Migraine is a debilitating chronic condition that affects most of the patient's existence, from childhood to late adulthood. During frequent headache attacks, its sufferers show marked increased sensitivity to noxious (hyperalgesia) and even non-noxious stimuli, a phenomenon called cutaneous allodynia that affects 63% of the patients. Although MRI-based techniques have provided insights into some brain mechanisms of migraine, many questions regarding its molecular impact in the brain are still unanswered. The overall goal of this project is to provide a detailed understanding of the µ-opioid receptor mediated transmission in the brain of migraine patients, one of the most important central pain regulatory systems in humans, with the long-term objective of developing more focused neuromechanism-driven methods for migraine research and therapy.

Preliminary studies from an earlier project (NINDS-NIHK23 NS0629946) using positron emission tomography (PET) with [11C] carfentanil, a selective radiotracer for μ-opioid receptor (μOR), have indicated that there is a decrease in µOR availability (non-displaceable binding potential; BPND) in the brain of migraine patients during the headache attacks and allodynia, including areas like thalamus and periaqueductal gray matter (PAG). µOR BPND is an objective measurement, in vivo, of endogenous μ-opioid availability, and its acute reduction reflects the activation of this neurotransmitter system. This is arguably one of the neuromechanisms most centrally involved in pain regulation, affecting multiple elements of the pain experience. Moreover, MRI-based reports have found that those findings co-localize with neuroplastic changes in migraine patients. Conventional therapies are unable to selectively target those dysfunctional brain regions, and there is a paucity of data on how to reverse embedded neuroplastic molecular mechanisms when available medications and surgical therapies fail. Several studies with motor cortex stimulation (MCS) have shown that epidural electrodes in the primary motor cortex (M1) are effective in providing analgesia in patients with refractory central. The rationale for MCS stimulation is based in part on the thalamic dysfunction noticed in chronic pain and migraine, and also on studies demonstrating that MCS significantly changes thalamic activity. Evidently, the invasive nature of such a procedure limits its indication to highly severe chronic pain disorders. New non-invasive brain neuromodulatory methods for M1, such as transcranial direct current stimulation (tDCS), can now safely modulate and activate the µOR system, providing relatively lasting pain relief in chronic pain patients and migraine. However, the electric fields generated by its most conventional analgesic montage are widely spread across the brain, lacking specificity on the pain-related structures directly targeted. Recently, a novel high-definition tDCS (HD-tDCS) montage created by our group was able to reduce exclusively "contralateral" sensory-discrimative clinical pain measures (pain intensity/area) in chronic patients by targeting more precisely the putative M1 region. It is hoped that this montage will provide durable relief of pain for this episodic migraine population.

This is a phase 2, single center, two-arm, double-masked, randomized investigation and modulation of the µ-opioid mechanisms in migraine (in vivo). We will enroll 60 patients with episodic migraine (30 for the active M1 HD-tDCS group and 30 for a sham group). Each participant will undergo a sequence of events and evaluations that will include baseline assessments, 10 days of HD-tDCS, pre- and post-PET and MRI scans, and questionnaires to evaluate pain and quality of life.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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 prophylactic medication for headaches and 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02964741


Contacts
Contact: Diana Burnett, MS, CCRC 734-615-9390 contactHOPE@umich.edu

Locations
United States, Michigan
University of Michigan School of Dentistry Recruiting
Ann Arbor, Michigan, United States, 48109-5720
Contact: Diana Burnett, MS, CCRC    734-615-9390    contactHOPE@umich.edu   
Principal Investigator: Alexandre F DaSilva, DDS, DMedSc         
Sponsors and Collaborators
University of Michigan
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
Principal Investigator: Alexandre F DaSilva, DDS, DMedSc University of Michigan
  More Information

Responsible Party: Alexandre DaSilva, DDS, MS, Assistant Professor of Biologic and Materials Science, School of Dentistry and Research Assistant Professor, Center for Human Growth & Development, University of Michigan
ClinicalTrials.gov Identifier: NCT02964741     History of Changes
Other Study ID Numbers: HUM00107286
R01NS094413 ( U.S. NIH Grant/Contract )
First Submitted: October 7, 2016
First Posted: November 16, 2016
Last Update Posted: March 30, 2017
Last Verified: November 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by Alexandre DaSilva, DDS, MS, University of Michigan:
Episodic Migraine
Headache
Opioid

Additional relevant MeSH terms:
Migraine Disorders
Headache Disorders, Primary
Headache Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents