Molecular and Functional PET-fMRI Measures of Analgesia in Migraine

• ClinicalTrials.gov Identifier: NCT01970943
• Recruitment Status: Completed
• First Posted: October 28, 2013
• Results First Posted: May 17, 2019
• Last Update Posted: May 17, 2019
• Sponsor: Massachusetts General Hospital
• Collaborators: National Institutes of Health (NIH); National Center for Complementary and Integrative Health (NCCIH)
• Information provided by (Responsible Party): David Borsook, Mclean Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Migraine; Healthy	Other: Placebo	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Basic Science
• Official Title: Molecular and Functional PET-fMRI Measures of Analgesia in Migraine
• Actual Study Start Date: September 1, 2012
• Actual Primary Completion Date: April 30, 2014
• Actual Study Completion Date: October 30, 2017

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Visual Analogue Scale (VAS) 0-10 Pain Rating [ Time Frame: 1 day ]

   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.

Secondary Outcome Measures :

1. Pain Anticipation fMRI BOLD Signal [ Time Frame: 1 day ]

   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

2. Pain Stimulation fMRI BOLD Signal [ Time Frame: 1 day ]

   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

3. PET Diprenorphine [ Time Frame: 1 day ]
   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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Massachusetts

Athinoula A. Martinos. Center for Biomedical Imaging

Charlestown, Massachusetts, United States, 02129

Sponsors and Collaborators

Massachusetts General Hospital

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

More Information

• Responsible Party: David Borsook, David Borosook, MD, Mclean Hospital
• ClinicalTrials.gov Identifier: NCT01970943
• Other Study ID Numbers: AT007530-01; R21AT007530-01 ( U.S. NIH Grant/Contract )
• First Posted: October 28, 2013
• Results First Posted: May 17, 2019
• Last Update Posted: May 17, 2019
• Last Verified: May 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by David Borsook, Mclean Hospital:

migraine, headache, episodic, chronic, pain

Additional relevant MeSH terms:

Migraine Disorders; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases