The Effects of Expectation and Knowledge on Rizatriptan and Placebo Treatment of Acute Migraine Headache

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.

Study Overview

• Status: Completed
• Conditions: Episodic Migraine
• Intervention / Treatment: Drug: Maxalt; Drug: placebo pill; Drug: placebo pills

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Brookline, Massachusetts, United States, 02445
      • Pain Clinic at Beth Israel Deaconess Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

• Exclusion criteria will include cardiovascular or cerebrovascular disorders,
• Cardiac risk factors and liver disease,
• Uncontrolled hypertension,
• Peripheral and central nervous system disorders that affect sensory functions (such as sensory neuropathies and chronic pain),
• The use of opiates or other analgesic drugs for any reason, and the use of other prophylactic anti-migraine drugs.
• Any patient with active hepatitis or elevated liver enzymes (based on their BIDMC medical record) will be excluded as well.
• Employees who are under the direct supervision of the investigators will not participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: 2	Drug: placebo pill; placebo pills
EXPERIMENTAL: 3	Drug: Maxalt; anti-migraine drug; Other Names: rizatriptan
PLACEBO_COMPARATOR: 4	Drug: placebo pills; placebo pills
EXPERIMENTAL: 1; Maxalt administration at onset of migraine	Drug: Maxalt; anti-migraine drug; Other Names: rizatriptan
EXPERIMENTAL: 5	Drug: Maxalt; anti-migraine drug; Other Names: rizatriptan
EXPERIMENTAL: 6	Drug: placebo pills; placebo pills

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	2 hours after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	2 hours after treatment

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Investigators: Principal Investigator: Rami Burstein, PhD, Beth Israel Deaconess Medical Center

Publications and helpful links

General Publications

• Kam-Hansen S, Jakubowski M, Kelley JM, Kirsch I, Hoaglin DC, Kaptchuk TJ, Burstein R. Altered placebo and drug labeling changes the outcome of episodic migraine attacks. Sci Transl Med. 2014 Jan 8;6(218):218ra5. doi: 10.1126/scitranslmed.3006175.

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (ACTUAL): December 1, 2013
• Study Completion (ACTUAL): December 1, 2013

Study Registration Dates

• First Submitted: July 18, 2008
• First Submitted That Met QC Criteria: July 18, 2008
• First Posted (ESTIMATE): July 21, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): April 9, 2015
• Last Update Submitted That Met QC Criteria: April 8, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Headache; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Serotonin Agents; Serotonin Receptor Agonists; Rizatriptan
• Other Study ID Numbers: 2007-P-000220