PARIS — A pilot study suggests that pretreatment with aspirin may help patients with multiple sclerosis (MS) access the benefits of exercise without the overheating that many experience with exertion.
Results of a randomized, placebo-controlled, crossover study in a small number of patients with MS showed only a small increase in the length of time spent exercising but a more substantial decrease in the number of patients describing themselves as heat sensitive who experienced an excessive increase in body temperature with exertion.
“This pilot study suggests that aspirin may represent an easy, economical treatment to enable people with MS to access the many benefits of exercise,” the researchers, with lead author, Victoria Leavitt, PhD, a neuropsychologist at Columbia University Medical Center and director of the Multiple Sclerosis Cognitive Neuroscience Laboratory in New York City, conclude.
The results were presented here at the7th Joint European Committee for Treatment and Research in Multiple Sclerosis-Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2017 meeting.
“We know that exercise is beneficial for people with MS on multiple levels — physical function, their gait, their balance, their mood, cognition,” Dr Leavitt told Medscape Medical News. “With all of that said, there’s one major obstacle to people with MS availing themselves of these benefits, which is that they don’t want to exercise because they overheat. It’s very uncomfortable for them, many of them.”
The discomfort arises from a well-known effect called Uhthoff’s phenomenon, described by German neuro-ophthalmologist Wilhelm Uhthoff in 1889, she said. He observed that after hot baths or exercise, patients with MS showed symptom worsening. Cooling patients down before or during exercise helps them exercise longer, but the treatments tested to date have involved “obtrusive and/or non-standardizable methods of peripheral cooling such as cold bath pre-cooling and vacuum hand-cooling chambers,” the authors note in their abstract.
While aspirin has been used before to reduce fatigue in patients with MS who are not exercising, “the idea of using aspirin as a pretreatment for its cooling mechanism is novel, so that’s never been done before in MS,” Dr Leavitt noted.
The effect of aspirin on body temperature in patients with MS at rest is thought to be related to its antipyretic effects, she noted, “but aspirin is pleiotropic, and it has many mechanisms: it’s anti-inflammatory, it’s analgesic.”
For this study, then, the researchers’ first objective was to see whether they could lengthen the time that patients with MS exercised. The second outcome of interest was to see whether aspirin administration could reduce the degree to which exercise increased patients’ body temperature.
The double-blind, randomized, placebo-controlled study used a crossover design to look at this question. Twelve patients were enrolled, eight of whom reported overheating during exercise. All attended two sessions of aerobic exercise. At each session, patients randomly took a standard dose (650 mg) of aspirin or a matching placebo.
After an hour, they performed a progressive ramped exercise test using a lower-body cycle ergometer to volitional exhaustion. The researchers then used paired-sample t-tests to compare differences in time to exhaustion between aspirin and placebo sessions, the primary endpoint, and the change in body temperature from pre- to postexercise by treatment.
“What we found was that after having been given aspirin, there was a 3% improvement in the time that they were able to keep exercising,” Dr Leavitt said. The mean time to exertion difference between groups was 16.4 ± 23.7 seconds (95% confidence interval, 1 – 31 seconds; t[11] = 2.405; P = .035 [Cohen’s d = 1.45]).
In patients identifying as heat-sensitive, the effect of aspirin was larger, she noted (t[7] = 3.321, P = .013 [Cohen’s d = 2.51; 95% CI, 7 – 44 seconds]).
They found that the secondary outcome of increase in exercise-induced body temperature did not differ between treatment groups in the overall sample.
“However, for people who had described themselves as being heat sensitive, we found that there was a reduction in the amount of body temperature increase that they experienced of 56%,” she said. “So this is very encouraging, as it’s perfectly aligned with our a priori hypothesis and the mechanism of antipyretic action that we thought aspirin would have.”
The next step for this approach is to isolate the mechanism, she noted. “I’m proposing a three-armed trial next, a large-scale trial, but adding in acetaminophen as a third arm, because acetaminophen has an antipyretic action but not the anti-inflammatory action, so that will get us closer to what’s driving the effect.”
Careful Evaluation
Commenting on these findings for Medscape Medical News, Katherine Costello, MS, a spokesperson for the National Multiple Sclerosis Society, said heat intolerance is very common among those with MS. “This phenomenon…causes people with MS to experience a temporary recrudescence of MS symptoms, often an increase in fatigue or other symptoms, such as weakness or cognitive problems,” Costello said.
“In this pilot study, it appeared that aspirin helped keep temperature lower than in the placebo group, and the longer time to exhaustion in the treated group may be due to the lower body temperature,” she said.
She cautioned, though, that this was a small study, and the results will have to be replicated in a larger trial.
“In addition, as aspirin can cause stomach irritation, careful evaluation of side effects will be important, particularly if this were to be considered as a treatment for heat intolerance related to exercise,” Costello added.
Dr Leavitt reports receiving grant funding from the National Multiple Sclerosis Society. Ms Costello is a spokesperson for the National Multiple Sclerosis Society.
7th Joint European Committee for Treatment and Research in Multiple Sclerosis-Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2017 meeting. Abstract P804. Presented October 26, 2017.
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