Healthy, Migraine
Conditions
Keywords
migraine, headache, episodic, chronic, pain
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.
Interventions
OTHERPlacebo
Placebo will be compared to No Intervention.
Sponsors
National Institutes of Health (NIH)
National Center for Complementary and Integrative Health (NCCIH)
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
21 Years to 50 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Visual Analogue Scale (VAS) 0-10 Pain Rating | 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
| Measure | Time frame | Description |
|---|---|---|
| Pain Anticipation fMRI BOLD Signal | 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 |
| Pain Stimulation fMRI BOLD Signal | 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 |
| PET Diprenorphine | 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. |
Countries
United States
Participant flow
Pre-assignment details
The study design was indeed crossover, but the cross-over was done immediately on the same day. In other words, participants were either scheduled to receive no intervention, and then placed placebo approximately 2 hours later to allow for washout. Or placed placebo first, and then no intervention approximately 2 hours later. No actual drug used.
Participants by arm
| Arm | Count |
|---|---|
| No Intervention PET-fMRI investigation on healthy subjects and patients with migraine. No drug condition and placebo (saline IV injection) | 23 |
| Total | 23 |
Baseline characteristics
| Characteristic | No Intervention |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants |
| Age, Continuous | 27 years STANDARD_DEVIATION 5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Region of Enrollment United States | 23 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 23 | 0 / 23 |
| serious Total, serious adverse events | 0 / 23 | 0 / 23 |
Outcome results
Primary
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.
Time frame: 1 day
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| No Intervention | Visual Analogue Scale (VAS) 0-10 Pain Rating | 4.3 units on a scale | Standard Deviation 2.4 |
| Placebo | Visual Analogue Scale (VAS) 0-10 Pain Rating | 7.2 units on a scale | Standard Deviation 2.8 |
Secondary
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
Time frame: 1 day
Population: 9 migraine subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| No Intervention | Pain Anticipation fMRI BOLD Signal | 0.5665 arbitrary units | Standard Deviation 0.8318 |
| Placebo | Pain Anticipation fMRI BOLD Signal | 1.1743 arbitrary units | Standard Deviation 0.8447 |
p-value: 0.05t-test, 2 sided
Secondary
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
Time frame: 1 day
Population: 9 migraine subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| No Intervention | Pain Stimulation fMRI BOLD Signal | .5745 arbitrary units | Standard Deviation 0.8224 |
| Placebo | Pain Stimulation fMRI BOLD Signal | 1.1537 arbitrary units | Standard Deviation 0.8326 |
Secondary
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.
Time frame: 1 day
Population: 9 migraine subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| No Intervention | PET Diprenorphine | 1.251 standard uptake value | Standard Deviation 0.259 |
| Placebo | PET Diprenorphine | 1.214 standard uptake value | Standard Deviation 0.175 |
p-value: 0.05t-test, 2 sided