Molecular and Functional PET-fMRI Measures of Analgesia in Migraine

The placebo effect is a phenomenon that has experienced major advances of its understanding in the last decade. However, mechanisms of placebo analgesia in chronic pain patients have yet to be compared to healthy subjects. The investigators study aims to investigate the magnitude of placebo response and related opioid release in patients that suffer from episodic migraines as compared to healthy controls. In particular, the investigators are looking to map brain activity during placebo analgesia using modern brain imaging techniques such as functional Magnetic Resonance Imaging (fMRI) and Positron Emission Tomography (PET). The investigators hypothesis is that placebo response and the availability of opioid receptors is reduced in chronic migraine patients.

Study Overview

• Status: Completed
• Conditions: Healthy; Migraine
• Intervention / Treatment: Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Charlestown, Massachusetts, United States, 02129
      • Athinoula A. Martinos. Center for Biomedical Imaging

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Migraine patients with aura with acute episodic migraine meeting the IHS Classification ICHD-II criteria, 3-14 migraines per month.
• History of episodic migraine for at least 3 years
• Ages 21-50
• Male or Female
• Right Handed

Matched healthy subjects will also be recruited.

Exclusion Criteria:

• Other significant disease (systemic or CNS)
• Pregnancy
• Claustrophobia
• Weight >235 lbs (limit of MRI table)
• Significant drug including alcohol history (> 7 glasses of alcohol per week)
• Beck Depression Inventory II (BDI-II) score > 25 (moderate to severe depression)
• Any metal implants incompatible with MRI (including dental bridges, crowns, retainers, orthodontic devices e.g. braces, IUDs, aneurysm clips or other devices, tattoos containing metallic ink, cardiac pacemakers, prosthetic hear valves, other prostheses, neurostimulator devices, implanted infusion pumps, exposure to shrapnel or metal filings, cochlear implants, etc.)
• Previous significant research related exposure to ionizing radiation.
• History of allergy or adverse reaction to opioids
• Significant medical history of such as seizure disorder, diabetes, alcoholism, cardiac disease including coronary artery disease, psychiatric problems; drug addiction, respiratory problems, liver disease, etc.
• Positive drug of abuse screen (excluding medications currently prescribed for their clinical condition, e.g. opioids, benzodiazepines, etc.)
• Patients with migraine <72 hours prior to the experiments will not be included to ensure inter-ictal state.
• Opioids or preventative medication such as topiramate, SSRIs etc.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: No Intervention; PET-fMRI investigation on healthy subjects and patients with migraine. No drug condition.
Placebo Comparator: Saline Injection (Placebo); PET-fMRI investigation on healthy subjects and patients with migraine. Placebo condition.	Other: Placebo; Placebo will be compared to No Intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Analogue Scale (VAS) 0-10 Pain Rating	This study will investigate how placebo may reduce experimental pain induced by contact heat. Patients rate heat stimulus intensity on a 0-10 scale, where 0 is no pain, and 10 is most intense pain possible. Data is reported to the placebo condition. The Visual Analogue Scale (VAS) consists of a straight line with the endpoints defining extreme limits such as 'no pain at all' and 'most intense pain possible'. The patient is asked to mark his pain level on the line between the two endpoints.	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Anticipation fMRI BOLD Signal	We imaged the subjects under an MRI scan. All data was collected on a Siemens 3 Tesla MR scanner using a PETcompatible eight-channel head coil. Structural T1 weighted MPRAGE Functional scans were preprocessed using slice timing correction, realignment, normalization, and smoothing (8 mm FWHM Gaussian filter), using SPM12. In each condition (placebo & no drug) subjects underwent four sets of pain anticipation at high and low temperatures (somatosensory control condition). The stimuli were modeled as boxcar time series, with additional regressors for temperature ramp-up, ramp-down, pain rating sequence, and six motion regressors.data were collected for each of the two PET-MR scans. Contrasts analyzed included pain anticipation. The values for the 8 sets of anticipation, for both the migraine and the healthy group are combined	1 day
Pain Stimulation fMRI BOLD Signal	We imaged the subjects under an MRI scan. All data was collected on a Siemens 3 Tesla MR scanner using a PETcompatible eight-channel head coil. Structural T1 weighted MPRAGE Functional scans were preprocessed using slice timing correction, realignment, normalization, and smoothing (8 mm FWHM Gaussian filter), using SPM12. In each condition (placebo & no drug) subjects underwent four sets of pain stimulation at high and low temperatures (somatosensory control condition). The stimuli were modeled as boxcar time series, with additional regressors for temperature ramp-up, ramp-down, pain rating sequence, and six motion regressors.data were collected for each of the two PET-MR scans. Contrasts analyzed included pain stimulation. The values for the 8 sets of stimulation, for both the migraine and the healthy group are combined	1 day
PET Diprenorphine	We sought to find if endogenous opioid levels and endogenous opioid release induced by placebo administration differentiates between the no intervention first, then placebo group compared to the placebo first, then no intervention group in migraine patients.	1 day

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: National Institutes of Health (NIH); National Center for Complementary and Integrative Health (NCCIH)
• Investigators: Principal Investigator: David Borsook, MD, Ph.D, Boston Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2012
• Primary Completion (Actual): April 30, 2014
• Study Completion (Actual): October 30, 2017

Study Registration Dates

• First Submitted: May 23, 2013
• First Submitted That Met QC Criteria: October 22, 2013
• First Posted (Estimate): October 28, 2013

Study Record Updates

• Last Update Posted (Actual): May 17, 2019
• Last Update Submitted That Met QC Criteria: May 15, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: migraine, headache, episodic, chronic, pain
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: AT007530-01; R21AT007530-01 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No