To test aspirin as a precooling treatment to reduce overheating and improve exercise performance in patients with multiple sclerosis.

Exercise is beneficial for people with MS (pwMS), many of whom avoid it due to overheating. Cooling therapy improves exercise performance and increases physical activity in pwMS. Aspirin is antipyretic; we hypothesized aspirin as an effective cooling treatment for exercise. Acetaminophen was included for comparison. 

This is a phase-3 double-blind placebo-controlled trial of aspirin for exercise. Eligible patients had relapsing-remitting MS and reported heat sensitivity. At each of three study visits, participants received 650-mg of aspirin, acetaminophen, or placebo, waited one hour, and completed a cycle ergometer maximal exercise test. Primary outcomes: total time-to-exhaustion (TTE), change in body temperature from pre- to post-test. Secondary outcomes: self-reported perceived exertion (breathing and muscle fatigue), pain, and fatigue; heart rate, systolic and diastolic blood pressure, peak minute ventilation, maximum watts, and respiratory exchange ratio (RER). Mixed-linear effects regression models accounting for repeated measures were used to compare outcomes across treatment groups.

60 patients were enrolled; 37 completed at least one study visit and were included in analysis. Controlling for session effects, differences were shown between aspirin and placebo for all primary and secondary outcomes. Aspirin pretreatment resulted in 79.3% decrease in exercise-induced body temperature increase (p<0.001) compared to placebo. Total TTE decreased after aspirin (396.2 +/- 47.3 seconds) compared to placebo (534.0 +/- 43.7). Aspirin pretreatment lowered perceived exertion, pain, fatigue, peak minute ventilation, RER, total watts, diastolic blood pressure, and heart rate. Acetaminophen reduced body temperature increase by 56.9%; TTE after acetaminophen did not differ from placebo.

Aspirin and acetaminophen are effective, accessible, relatively safe, and affordable cooling treatments to permit many pwMS to benefit from exercise. Wide recognition, recommendation, and uptake of this simple treatment is the next challenge.