Aspirin for MS-Related Fatigue

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

B. Mark Keegan, M.D., a neurologist and MS specialist at Mayo Clinic in Rochester, Minn., says 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, and problems that disturb sleep, including nocturia and sleep apnea. Current medications for MS-related fatigue include amantadine, modafinil, and other stimulants, but Dr. Keegan notes that none of them addresses underlying fatigue mechanisms.

Ten years ago, Dean M. Wingerchuk, M.D., a neurologist and MS specialist at Mayo Clinic in Scottsdale, Ariz., and his colleagues noted that some patients taking moderately high doses of aspirin for coexisting conditions such as rheumatoid arthritis reported more energy and less fatigue. They also reported that with reduced doses of aspirin, fatigue worsened.

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

Dr. Wingerchuk, principal investigator, explains: "For many years, people 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 thus help us understand the relevant mechanisms in MS."

Open clinical trial

The goals of the current study are to determine the efficacy and magnitude of aspirin's effect of aspirin on MS-related fatigue. A second goal is to more precisely quantify fatigue in order 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
• 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, which includes Moses Rodriguez, M.D., in Rochester and Elizabeth A. Shuster, M.D., in Jacksonville, Fla., hopes that in addition to the stated goals, the study will shed light on the role of inflammation in MS-related fatigue.