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A randomized controlled trial of oral antipyretic treatment to reduce overheating during exercise in adults with multiple sclerosis

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Abstract

Background

Some people with multiple sclerosis (pwMS) avoid exercise due to overheating. Evidence from a variety of cooling treatments shows benefits for pwMS.

Objective

Conduct a randomized controlled trial of antipyretic treatment before exercise in pwMS.

Methods

Adults over age 18 diagnosed with relapsing–remitting MS reporting heat sensitivity during exercise were randomly assigned to one of six sequences counterbalancing aspirin, acetaminophen, placebo. At each of three study visits separated by ≥ one week, participants received 650-millograms of aspirin, acetaminophen, or placebo before completing a maximal exercise test. Primary outcomes were body temperature change and total time-to-exhaustion (TTE), secondary outcomes were physiological and patient-reported outcomes (PROs).

Results

Sixty participants were enrolled and assigned to treatment sequence; 37 completed ≥ one study visit. After controlling for order effects, we found that body temperature increase was reduced after aspirin (+ 0.006 ± 0.32 degrees Fahrenheit, p < 0.001) and after acetaminophen (+ 0.31 ± 0.35; p = 0.004) compared to placebo (+ 0.68 ± 0.35). TTE after aspirin (331.6 ± 76.6 s) and acetaminophen (578.2 ± 82.1) did not differ significantly from placebo (551.0 ± 78.4; p’s > 0.05). Aspirin benefited all secondary outcomes compared to placebo (all p’s < 0.001); acetaminophen showed broadly consistent benefits.

Conclusion

These results support antipyretic treatment as effective for reducing overheating during exercise in pwMS and failed to support antipyretics for increasing TTE in the context of a maximal exercise test. Benefits were shown for physiological markers of exercise productivity and PROs of fatigue, pain, and perceived exertion.

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Data availability

De-identified participant data will be made available to qualified investigators upon reasonable request to the study PI (VML).

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Acknowledgements

The authors wish to acknowledge and thank the clinical team at the Multiple Sclerosis Center at Columbia University Irving Medical Center (CUIMC) for their help recruiting patients for this study, especially Rebecca Straus Farber, and the team of exercise physiologists within the CUIMC Department of Rehabilitation and Regenerative Medicine, especially Nancy Lee and Scott Barbuto. We wish to acknowledge clinical trial training support of R25 NS088248 and U01 NS077352. Finally, we thank the MS patients who participated in this study for their enthusiastic support.

Funding

This work was supported by a grant from the National Institutes of Health (National Center for Medical Rehabilitation Research within the National Institute of Child Health and Human Development) to VML (HD091836-01A1). The funding source had no role in interpretation of the study results.

Author information

Authors and Affiliations

  1. Cognitive Neuroscience Division, Department of Neurology, Columbia University Irving Medical Center, New York, NY, 10032, USA

    Victoria M. Leavitt

  2. Department of Radiology, Weill Cornell Medicine, New York, NY, USA

    Ceren Tozlu

  3. Multiple Sclerosis Center, Department of Neurology, Columbia University Irving Medical Center, New York, USA

    Katherine E. Nelson, Jaime E. Donnelly, Ines Aguerre, Claire S. Riley & Kaho Onomichi

  4. Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, USA

    Katherine E. Nelson, Claire S. Riley & Kaho Onomichi

  5. Department of Neurology and Epidemiology, Columbia University Irving Medical Center, New York, USA

    Amelia K. Boehme

  6. Department of Rehabilitation and Regenerative Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA

    Michael Spinner & Joel Stein

Authors
  1. Victoria M. Leavitt
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  2. Ceren Tozlu
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Correspondence to Victoria M. Leavitt.

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Leavitt, V.M., Tozlu, C., Nelson, K.E. et al. A randomized controlled trial of oral antipyretic treatment to reduce overheating during exercise in adults with multiple sclerosis. J Neurol 271, 2207–2215 (2024). https://doi.org/10.1007/s00415-023-12147-6

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  • DOI: https://doi.org/10.1007/s00415-023-12147-6

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