Aspirin for Exercise in Multiple Sclerosis (ASPIRE)

Study Overview
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Brief Summary
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This study investigates the use of aspirin as an exercise pre-treatment to reduce overheating and exhaustion, which may potentially allow many more people with multiple sclerosis to participate in and benefit from exercise. The design is double-blind, within-subject, with three arms: participants will receive one of three treatments at three separate study visits: aspirin, acetaminophen, and placebo, followed by completion of a maximal exercise test.

Detailed Description
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Persons with multiple sclerosis benefit from exercise, but many avoid it because of exhaustion and overheating. This randomized controlled trial (RCT) tests aspirin as a method to increase time to exhaustion for persons with MS, through its antipyretic mechanism. Participants will be seen at our laboratory for maximal exercise tests on three separate days. At each session, they will be given one of three treatments: aspirin, acetaminophen (a drug that is anti-inflammatory but not antipyretic, thereby allowing for isolation of the antipyretic action of aspirin), and placebo. Primary outcome is increased time to exhaustion, secondary outcome is reduced body temperature increase during exercise.

Official Title
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Aspirin for Exercise in Multiple Sclerosis (ASPIRE): A Double-Blind RCT of Aspirin or Acetaminophen Pretreatment to Improve Exercise Performance in Multiple Sclerosis (MS)

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Aspirin 650mg Oral Capsule
* Drug: Acetaminophen Tablet 650mg
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of relapsing-remitting MS self-reported heat-sensitivity to exercise Expanded Disability Status Scale (EDSS) total score ≤ 6.0 exacerbation-free (and no use of corticosteroids) for 6 weeks prior BMI ≤ 40 Exclusion Criteria: prior history of significant head injury, stroke, or other neurological disease/disorder current daily use of antipyretics or pain medication currently in a major depressive episode vascular disease of the legs, uncontrolled high blood pressure uncontrolled diabetes mellitus or problem with blood sugar levels contraindications to aspirin use (history of confirmed peptic ulcer, gastrointestinal or severe gynecological bleeding) tarry stool or known fecal occult blood uncontrolled syndrome of asthma, rhinitis, or nasal polyps contraindications to acetaminophen use (severe active hepatic disease, Hepatitis C Virus)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This is a within-subject design double-blind RCT in which each participant receives 1 of 3 treatments at 3 timepoints (i.e., 3 separate days separated by 1-week washout periods).
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aspirin<br>Aspirin 650 mg capsule by mouth, single dose | Drug: Aspirin 650mg Oral Capsule<br>* A 650mg dose of aspirin is administered in the laboratory one hour before participant completes a maximal exercise test.<br>* Other names: Aspirin;|
| Active Comparator: Acetaminophen<br>Acetaminophen 650 mg capsule by mouth, single dose | Drug: Acetaminophen Tablet 650mg<br>* A 650mg dose of acetaminophen is administered in the laboratory one hour before participant completes a maximal exercise test.<br>* Other names: Acetaminophen;|
| Placebo Comparator: Placebo<br>Placebo 650 mg capsule by mouth, single dose | Other: Placebo<br>* A placebo pill is administered in the laboratory one hour before participant completes a maximal exercise test.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-to-exhaustion | Duration of time exercising before reaching peak exertion, defined as cadence drop below 40 revolutions per minute (RPM) for >/= 5 seconds, or patient reaches volitional exhaustion in accordance with American Thoracic Society standard test termination criteria. | from start of exercise test until self-reported exhaustion, up to 30 minutes | 
| Exercise-induced Body Temperature Change | Change in body temperature from pre- to post- maximal exercise test. | from start of exercise test until self-reported exhaustion, up to 30 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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exercise, aspirin, cooling, antipyretic