Episodic Migraine
Conditions
Brief summary
Evidence-based medicine depends on distinguishing between pharmacological effects and placebo effects in randomized controlled trials (RCT). This proposal seeks to rigorously investigate fundamental questions concerning pharmacological effects, placebo effects and their interactions. Relief of symptoms of acute migraine will be the test condition for this scientific experiment because of migraine's evident clinical significance and the possibility of using participants as their own control during sequential acute migraine attacks. Our overall goal is to elucidate how the pharmacological effects of 100 mg rizatriptan (an FDA-proven effective medication for acute migraine) and the effects of placebo treatment can be modified by varied knowledge and/or expectation (contextual) conditions. Such knowledge has the possibility to suggest potentially more efficient methodologies to test new medications that can be used to augment and enhance the apparatus of the RCT. General Aim: To elucidate and clarify what is a pharmacological effect and what is a placebo effect, how such effects vary in different knowledge/expectations contexts, and mutually constitute one another and interact. General Hypothesis: The measured pharmacological effect of an effective medication (rizatriptan) and the measured effect of placebo treatment are determined significantly by different knowledge/expectations contexts.
Interventions
DRUGMaxalt
anti-migraine drug
DRUGplacebo pill
placebo pills
DRUGplacebo pills
placebo pills
Sponsors
Beth Israel Deaconess Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients will be considered for this study if they suffer from classical or common migraine for at least 3 years. * Candidates will recruited from the clinical case load of Dr. Zahid Bajwa and the headache and pain management center at BIDMC. * Only patients older than 18 years of age, * Able to communicate clearly in English, * Able to give an informed consent will be considered as candidates. * No limitation of gender or race is justified and thus, it is open to all patients fulfilling criteria for migraine type headache. * Patients will be able to withdraw from the study at any time. * They will be included in the study if they meet the criteria for migraine with or without aura (Headache-classification-committee-of-the-International-Headache-Society 1988), if they had \>4 migraine attacks each month for the previous year.
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Headache Intensity | 2 hours after treatment | The primary outcome measure was the change in headache between the baseline pain score recorded 30 min after the onset of headache and the pain score recorded 2 hours later as measured on a visual analog scale ranging from 0 (no pain) to 10 (worst pain imaginable). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Free at 2 Hours After Treatment | 2 hours after treatment | A secondary measure of attack outcome was based on categorical classification of the pain freedom (pain score = 0) 2.5 hours after onset of headache. |
Countries
United States
Participant flow
Recruitment details
Of 98 persons pre-screened for eligibility between December 2008 and March 2010, 19 were excluded and 3 declined to participate. The remaining 76 persons signed the consent form, but 10 of them dropped out of the study for various reasons. Participants were recruited from Beth Israel Deaconess Medical Center outpatient clinics.
Pre-assignment details
Reasons for excluding 19 of the pre-screened subjects include chronic migraine, chronic daily headache, tension type headache, fibromyalgia, daily use of opioids, and medication overuse headache. We randomized participants to one of 8 treatment sequences and each patient received 3 treatments with Maxalt and 3 treatments with Placebo.
Participants by arm
| Arm | Count |
|---|---|
| All Participants 76 subjects were randomized to 8 different treatment sequences. Each sequience included treating 6 attacks. 66 subjects completed their treatment assignment. | 76 |
| Total | 76 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 40.6 years STANDARD_DEVIATION 12.7 |
| Headache intensity | 4.6 units on a scale STANDARD_DEVIATION 1.8 |
| Region of Enrollment United States | 76 participants |
| Sex: Female, Male Female | 65 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 | 11 / 66 | 11 / 66 |
| serious Total, serious adverse events | 0 / 66 | 0 / 66 |
Outcome results
Primary
Change in Headache Intensity
The primary outcome measure was the change in headache between the baseline pain score recorded 30 min after the onset of headache and the pain score recorded 2 hours later as measured on a visual analog scale ranging from 0 (no pain) to 10 (worst pain imaginable).
Time frame: 2 hours after treatment
Population: For the primary endpoint, change in headache intensity from baseline to 2 hours after treatment, we used generalized linear mixed models with a normal random component and a logarithmic link function to analyze the pain scores.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| All Participants | Change in Headache Intensity | percent change with Maxalt | -47.6 percent change |
| All Participants | Change in Headache Intensity | percent change with placebo | -20.7 percent change |
Secondary
Pain Free at 2 Hours After Treatment
A secondary measure of attack outcome was based on categorical classification of the pain freedom (pain score = 0) 2.5 hours after onset of headache.
Time frame: 2 hours after treatment
Population: For the secondary endpoint, the proportion of patients who were free from pain 2 hours after treatment, we used a mixed-effects logistic regression model to analyze the individual dichotomous outcomes.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Participants | Pain Free at 2 Hours After Treatment | pain free with maxalt | 25.5 percent of patients pain free |
| All Participants | Pain Free at 2 Hours After Treatment | pain free with placebo | 6.6 percent of patients pain free |