Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Aspirin Resistance in Women With Migraine (ARWM)

This study has been withdrawn prior to enrollment.
Sponsor:
Collaborators:
University of Washington
National Headache Foundation
Wadsworth Foundation
Accumetrics, Inc.
Information provided by:
Swedish Medical Center
ClinicalTrials.gov Identifier:
NCT01257893
First received: December 8, 2010
Last updated: May 29, 2013
Last verified: May 2013
  Purpose

The purpose of this study is to compare the rates of aspirin resistance (high residual platelet reactivity) between women with episodic and chronic migraine and women without migraine.

Emerging evidence suggests that migraineurs, especially women < 45 years who have aura, have an increased risk of stroke and myocardial infarction (MI, or heart attack). The mechanism linking migraine, stroke and MI is unclear although increased platelet activation and aggregation observed during and between migraine attacks may be a plausible theory.

Aspirin is an inexpensive, relatively safe antiplatelet drug that reduces the risk of stroke and MI. Preliminary data suggest that aspirin's (325mg) therapeutic effect on platelet inhibition may be reduced in migraineurs (i.e., aspirin resistance), thus limiting aspirin's effectiveness at preventing stroke and MI risks in persons with migraine. Additional research is warranted to confirm these findings in migraineurs because daily, low-dose aspirin 81 mg is the recommended first line therapy for primary and secondary prevention of stroke and MI

The researchers hypothesize that resistance to aspirin 81mg may occur more frequently in women with episodic and chronic migraine than in women without migraine. The findings may have important implications for women who have migraine and use aspirin to prevent migraine symptoms or comorbidities associated with migraine including stroke and MI.


Condition Intervention
Episodic Migraine
Chronic Migraine
Drug: Aspirin (acetylsalicylic acid)
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Screening
Official Title: Aspirin Resistance in Women With Migraine

Resource links provided by NLM:


Further study details as provided by Swedish Medical Center:

Primary Outcome Measures:
  • Aspirin Reaction Units (ARU) [ Time Frame: 10-14 days ] [ Designated as safety issue: No ]
    Measurement of ARU, indicative of platelet inhibition, using the VerifyNow Aspirin Assay (Accumetrics, San Diego, CA)


Secondary Outcome Measures:
  • Serum thromboxane B2 [ Time Frame: 10-14 days ] [ Designated as safety issue: No ]
    Aspirin acts by inhibiting production of thromboxane A2 by platelets. Thromboxane B2 is the stable product of thromboxane A2.


Enrollment: 0
Study Start Date: November 2010
Study Completion Date: August 2012
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aspirin 81 mg
Subjects will take 81 mg aspirin per day for 10-14 consecutive days
Drug: Aspirin (acetylsalicylic acid)
Aspirin one 81 mg capsule per day for 10-14 consecutive days
Placebo Comparator: Placebo
Subjects will take matching placebo capsule (excipient: methylcellulose) for 10-14 consecutive days.
Drug: Placebo
1 placebo capsule identical in appearance and excipient to aspirin capsule per day for 10-14 consecutive days

Detailed Description:

To test the hypothesis that the rate of aspirin resistance is greater in women with episodic and chronic migraine than in women without migraine, a three-group, randomized, double-blind, placebo-controlled, crossover design will be used to test the effects of aspirin 81 mg on platelet reactivity. Subjects will be randomized to treatment order (A) aspirin 81 mg for 10-14 consecutive days followed by placebo for 10-14 consecutive days or (B) placebo for 10-14 consecutive days followed by aspirin 81 mg for 10-14 consecutive days. Other than treatment order, subjects will be treated equally. Study procedures will be performed at the University of Washington, and the duration of the study per subject will be approximately 28 days. Endpoints include: a) Aspirin Reaction Units (ARU) using a point-of-care assay (VerifyNow Aspirin™; Accumetrics, San Diego, CA); b) serum thromboxane B2; and c) percent platelet inhibition on aspirin. Assessment of adherence to study regimen will be assessed by serum salicylate, medication diaries, and pill counts. Data will also be collected on migraine frequency, burden, disability, and medications used to treat headache. Subjects will maintain a migraine diary for the duration of the study (28 days). The target sample will include women with episodic migraine (n=40; n=20 MA, n=20 MO), women with chronic migraine (n=40) and non-migraine controls (n=40).

The specific aims of the study are as follows:

  • Compare the rate of aspirin resistance between women with and without migraine following 10-14 consecutive days of aspirin 81 mg treatment
  • Compare the rate of aspirin resistance between women who have episodic migraine and chronic migraine following 10-14 consecutive days of aspirin 81 mg treatment
  • Compare the rate of aspirin resistance between women who have migraine with aura (MA) and migraine without aura (MO) following 10-14 consecutive days of aspirin 81 mg or placebo treatment
  • Compare the rate of aspirin resistance between women who have migraine with high monthly migraine frequency and low monthly migraine frequency following 10-14 consecutive days of aspirin 81 mg treatment
  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Women 18-50 years of age, of childbearing potential
  • Able to read, speak, and understand English -- except if patient is blind, in which case only the ability to understand English is required.

Episodic Migraine Group:

  • Documented diagnosis of episodic migraine for a 2-year period preceding enrollment, using the International Headache Society (IHS) criteria.
  • Frequency of 2-14 migraine days in the three months prior to enrollment.
  • Equal numbers (n=20 each) will have a documented diagnosis of migraine with aura (MA) and migraine without aura (MO).
  • For women who have a diagnosis of MA, focal neurologic symptoms must precede or accompany the headache (aura) for at least one headache in the 12 months prior to enrollment.

Chronic Migraine Group:

  • Frequency of ≥ 15 headache days per month for ≥ 3 months.
  • On at least 8 days per month for ≥ 3 months headache has fulfilled criteria for pain and associated symptoms of MO.

Control group:

- No diagnosis of migraine, confirmed by the Migraine Assessment Tool.

Exclusion Criteria:

  • Pregnancy or lactation
  • Post-menopausal, either natural or surgical (bilateral oophorectomy)
  • Current prescribed daily medication regimen includes any of the following: warfarin, glycoprotein IIb/IIIa inhibitors (abciximab, tirofiban), antiplatelet agents (clopidogrel, ticlopidine, dipyridamole), or non-steroidal anti-inflammatory drugs (e.g., ibuprofen, naproxen, celecoxib), Vitamin E in doses > 800 IU per day, Omega-3 fatty acids in doses > 3 g/day, willow bark (any amount), aspirin or aspirin-containing medications.
  • Aspirin intolerance or allergy, or peptic ulcer disease.
  • Platelet count <150,000/µl or >450,000/µl.
  • Hemoglobin <10 g/dL.
  • History or current diagnosis of myocardial infarction, stroke, coronary artery disease, peripheral arterial disease, diabetes mellitus, or renal disease.
  • Unable to tolerate washout of protocol-restricted medications and/or supplements (see #3).
  • Family (first-degree relative) or patient history of bleeding or hemorrhagic disorders including von Willebrand Factor Deficiency, Glanzmann Thrombasthenia, Bernard-Soulier Syndrome or myeloproliferative syndromes.
  • Major surgical procedure, trauma, blood donation, or major blood loss (>300 cc) within 30 days prior to enrollment.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01257893

Locations
United States, Washington
The University of Washington
Seattle, Washington, United States, 98195
Sponsors and Collaborators
Swedish Medical Center
University of Washington
National Headache Foundation
Wadsworth Foundation
Accumetrics, Inc.
Investigators
Principal Investigator: Jill T. Jesurum, Ph.D. Swedish Medical Center
Study Director: Cindy J. Fuller, Ph.D. Swedish Medical Center
Study Chair: Sylvia M. Lucas, MD, PhD University of Washington
Study Chair: Natalia Murinova, MD University of Washington
  More Information

Publications:
Jesurum, J.T., Fuller, C.J., Lucas, S.M., Murinova, N., Truva, C.M., McGee, E.A., Reisman, M. High prevalence of aspirin resistance in migraineurs. Cephalalgia 2009; 29 (Suppl. 1): 138.
Jesurum, J.T., Fuller, C.J., Lucas, S.M., Murinova, N., Hales, L.E., McGee, E.A. The association between migraine frequency and platelet activation in episodic migraine: a pilot study. Cephalalgia 2009; 29 (Suppl. 1); 2009.

Responsible Party: Jill T. Jesurum, Ph.D., Scientific Director, Swedish Medical Center
ClinicalTrials.gov Identifier: NCT01257893     History of Changes
Other Study ID Numbers: 4959S-10
Study First Received: December 8, 2010
Last Updated: May 29, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Swedish Medical Center:
migraine
chronic migraine
migraine with aura
migraine without aura
aspirin
platelets

Additional relevant MeSH terms:
Migraine Disorders
Brain Diseases
Central Nervous System Diseases
Headache Disorders
Headache Disorders, Primary
Nervous System Diseases
Aspirin
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antipyretics
Antirheumatic Agents
Cardiovascular Agents
Central Nervous System Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014