Aspirin for multiple sclerosis–related fatigue

Points to remember

• Researchers have postulated that because multiple sclerosis (MS) is an autoimmune disease, inflammation might be a key factor in the pathogenesis of MS-related fatigue.
• Mayo Clinic neurologists have noted that some patients taking moderately high doses of aspirin for coexisting conditions such as rheumatoid arthritis reported more energy and less fatigue.
• After conducting a small pilot study, Mayo Clinic researchers are enrolling patients in a larger study funded by the National Multiple Sclerosis Society to determine the efficacy and magnitude of the effect of aspirin on MS-related fatigue.

Fatigue is one of the most common and debilitating symptoms of MS. It can affect concentration, muscle strength, and psychosocial well-being. The mechanisms are not understood and may differ among patients. Few medications are available, and even these may be ineffective for many patients.

Mayo Clinic neurologists advise that before prescribing medications, it is important to rule out common factors that may contribute to fatigue in MS patients, such as:

• Depression
• Drug therapies
• Problems that disturb sleep, including nocturia and sleep apnea

Current medications for MS-related fatigue include amantadine, modafinil, and other stimulants, but none of them addresses underlying fatigue mechanisms.

Ten years ago, Mayo Clinic neurologists noted that some patients taking moderately high doses of aspirin for coexisting conditions such as rheumatoid arthritis reported more energy and less fatigue. The patients also reported that with reduced doses of aspirin, fatigue worsened.

For many years, researchers have postulated that since MS is an autoimmune disease, inflammation might be a key factor in the pathogenesis of MS-related fatigue. The well-understood anti-inflammatory mechanisms of aspirin may help researchers understand the relevant mechanisms in MS.

From this clinical observation, a Mayo research team designed a pilot study of 30 patients. Fatigue levels were measured by patient self-report. Results showed aspirin was effective compared with a placebo.

Open clinical trial

To replicate, expand, and further objectify their findings, the research team is now conducting a larger study, funded by the National Multiple Sclerosis Society and carried out at all 3 Mayo Clinic sites.

The primary goal of the current study is to determine the efficacy and magnitude of the effects of aspirin on MS-related fatigue. A secondary goal is to more precisely quantify fatigue to develop objective measures of therapeutic outcome.

In addition to a standard self-report questionnaire, participants will be given cognitive tests of memory and concentration, blood tests to measure inflammation markers, and at the Arizona site, tests of muscle fatigue conducted in a biomechanics laboratory.

To participate, patients must:

• Be between 18 and 65 years old
• Have confirmed relapsing remitting or secondary progressive MS
• Be ambulatory for a distance of at least 100 meters without assistance
• Have had persistent fatigue for 8 weeks not attributable to causes other than MS
• Be able to complete cognitive testing and questionnaires

Exclusionary criteria include medical contraindications for aspirin, factors related to other causes of fatigue, and general health problems. Participants who meet enrollment criteria are placed in 1 of 3 groups and given a high dose (1,300 mg/day) or low dose (162 mg/day) of aspirin or a placebo over an 8-week course.

The Mayo research team hopes that in addition to the stated goals, the study will shed light on the role of inflammation in MS-related fatigue.