Aspirin for Exercise in Multiple Sclerosis (ASPIRE)

Sponsor

Columbia University (Other)

Overall Status

Completed

CT.gov ID

NCT03824938

Collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)

Enrollment

Location

Arms

Actual Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis	Drug: Aspirin 650mg Oral Capsule Drug: Acetaminophen Tab 650mg Other: Placebo	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention 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).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 (Outcomes Assessor)

Masking Description:

Study biostatistician will derive the randomization schedule. Study pharmacy will make assignments and maintain blinding until data analysis is complete for the full sample.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 30, 2019

Actual Primary Completion Date :

Feb 28, 2022

Actual Study Completion Date :

Feb 28, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aspirin Aspirin 650 mg capsule by mouth, single dose	Drug: Aspirin 650mg Oral Capsule A 650mg dose of aspirin is administered in the laboratory one hour before participant completes a maximal exercise test.
Active Comparator: Acetaminophen Acetaminophen 650 mg capsule by mouth, single dose	Drug: Acetaminophen Tab 650mg A 650mg dose of acetaminophen is administered in the laboratory one hour before participant completes a maximal exercise test.
Placebo Comparator: Placebo Placebo 650 mg capsule by mouth, single dose	Other: Placebo A placebo pill is administered in the laboratory one hour before participant completes a maximal exercise test.

Arm

Intervention/Treatment

Experimental: Aspirin

Aspirin 650 mg capsule by mouth, single dose

Drug: Aspirin 650mg Oral Capsule

A 650mg dose of aspirin is administered in the laboratory one hour before participant completes a maximal exercise test.

Active Comparator: Acetaminophen

Acetaminophen 650 mg capsule by mouth, single dose

Drug: Acetaminophen Tab 650mg

A 650mg dose of acetaminophen is administered in the laboratory one hour before participant completes a maximal exercise test.

Placebo Comparator: Placebo

Placebo 650 mg capsule by mouth, single dose

Other: Placebo

A placebo pill is administered in the laboratory one hour before participant completes a maximal exercise test.

Outcome Measures

Primary Outcome Measures

Time-to-exhaustion [from start of exercise test until self-reported exhaustion, up to 30 minutes]
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.

Secondary Outcome Measures

Exercise-induced body temperature increase [from start of exercise test until self-reported exhaustion, up to 30 minutes]
Change in body temperature from pre- to post- maximal exercise test

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)