Multiple Sclerosis
Conditions
Keywords
exercise, aspirin, cooling, antipyretic
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.
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.
Interventions
DRUGAspirin 650mg Oral Capsule
A 650mg dose of aspirin is administered in the laboratory one hour before participant completes a maximal exercise test.
DRUGAcetaminophen Tablet 650mg
A 650mg dose of acetaminophen is administered in the laboratory one hour before participant completes a maximal exercise test.
OTHERPlacebo
A placebo pill is administered in the laboratory one hour before participant completes a maximal exercise test.
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Columbia University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
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.
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).
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Exercise-induced Body Temperature Change | from start of exercise test until self-reported exhaustion, up to 30 minutes | Change in body temperature from pre- to post- maximal exercise test. |
Countries
United States
Participant flow
Recruitment details
Out of the 97 screened, 60 were enrolled in the study.
Pre-assignment details
Out of the 60 enrolled, 37 completed at least one visit.
Participants by arm
| Arm | Count |
|---|---|
| All Participants ASPIRE trial sample characteristics of the 37 active study participants. | 37 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 0 | 2 | 0 | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 42.3 years STANDARD_DEVIATION 11.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 31 Participants |
| Region of Enrollment United States | 37 participants |
| Sex: Female, Male Female | 30 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 31 | 0 / 32 |
| other Total, other adverse events | 0 / 32 | 0 / 31 | 0 / 32 |
| serious Total, serious adverse events | 0 / 32 | 0 / 31 | 0 / 32 |
Outcome results
Primary
Exercise-induced Body Temperature Change
Change in body temperature from pre- to post- maximal exercise test.
Time frame: from start of exercise test until self-reported exhaustion, up to 30 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Exercise-induced Body Temperature Change | 0.68 degrees Fahrenheit | Standard Deviation 0.35 |
| Aspirin | Exercise-induced Body Temperature Change | 0.006 degrees Fahrenheit | Standard Deviation 0.32 |
| Acetaminophen | Exercise-induced Body Temperature Change | 0.31 degrees Fahrenheit | Standard Deviation 0.35 |
Primary
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.
Time frame: from start of exercise test until self-reported exhaustion, up to 30 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Time-to-exhaustion | 551.7 seconds | Standard Deviation 78.4 |
| Aspirin | Time-to-exhaustion | 331.6 seconds | Standard Deviation 76.6 |
| Acetaminophen | Time-to-exhaustion | 578.2 seconds | Standard Deviation 82.1 |