Aspirin for Treatment of Multiple Sclerosis-Related Fatigue

Fatigue is the most common symptom of multiple sclerosis (MS), affecting up to 90% of people
with the disease. MS-related fatigue can be disabling even when other features of MS are
mild. It can interfere with physical activity, memory and thinking, social and family
activities, and ability to work. Initial treatment consists of energy conservation
techniques such as rest periods or naps but when these approaches fail doctors usually
recommend a trial of medications. Amantadine, modafinil, and other stimulants are commonly
used but help only about half of those who try them. It is unlikely that these drugs
directly affect the cause of MS-related fatigue.

It has been difficult to develop new drug therapies for MS-related fatigue because we do not
fully understand its causes and do not have precise ways to measure it. We rely on a
person?s self-report about their fatigue but individuals experience and report fatigue
differently. Recent research has shown that some fatigue aspects, such as difficulty
maintaining mental concentration (?cognitive fatigue?) and physical activity (?motor
fatigue?), can be measured more precisely and require further study.

We recently reported results from a study showing that people taking the equivalent of four
regular aspirin tablets (1300 mg) daily had reduced MS-related fatigue compared with placebo
(sugar pill). The current proposal will attempt to confirm the benefit of aspirin in a
larger group of people and to determine if the benefit is related to inflammation. One
hundred and thirty-five people with MS-related fatigue will participate at MS clinics at
three Mayo Clinic sites. Participants will complete questionnaires that ask about the
severity and impact of their fatigue, memory testing to assess cognitive fatigue, and have
blood testing to measure markers of inflammation. At the Arizona site, participants will
also do strength testing in a motor laboratory to assess motor fatigue. After obtaining two
separate baseline evaluations, the participants will be randomly assigned treatment such
that one-third will receive 1300 mg per day of aspirin, one-third will receive 162 mg per
day of aspirin and one-third will receive a matching placebo. All participants will then
return to the clinic on two more occasions over the next eight weeks to repeat the
questionnaires, memory and strength testing, blood tests, and report any side-effects. At
the end of the study, the results of one of the fatigue questionnaires will be analyzed to
determine if aspirin significantly improved fatigue compared with the placebo. The results
of other questionnaires and the memory and strength testing will be analyzed as supportive
evidence.

If this study is successful, it will provide strong scientific evidence that aspirin helps
MS-related fatigue. It will add an important new option for treatment of all MS patients
that is also familiar, inexpensive, and has a good long-term safety record. At the same
time, it will allow us to better understand the causes of MS-related fatigue and how to
measure it more precisely. This information will be extremely useful for development of
other therapies in the future.

Inclusion criteria:

- Confirmed relapsing-remitting or secondary progressive multiple sclerosis,

- Ambulatory for distance of at least 100 m without gait assistance,

- Persistent fatigue for at least 8 weeks that is not attributable to causes other than
MS, and

- Will be able to complete questionnaires and cognitive testing.

Exclusion criteria:

- Other evident causes for fatigue,

- Recent MS disease activity or specific changes in MS therapy,

- Current use of ASA or other NSAIDs,

- Use of CNS stimulants,

- Use of medications that contraindicate the use of ASA, ASA allergy or sensitivity,

- History of peptic ulcer disease or GI bleed,

- Alcohol abuse,

- Pregnancy, and

- Laboratory abnormalities.