Aspirin for Treatment of Multiple Sclerosis-Related Fatigue

Inclusion criteria: * Confirmed relapsing-remitting or secondary progressive multiple sclerosis, * Ambulatory for distance of at least 100 meters 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: 1. Other evident causes for fatigue: * Untreated depression or screening Center for Epidemiologic Studies Depression (CES-D) scale greater than 28 * Significant cognitive impairment (Baseline Short Test of Mental Status score of less than 29/38) * Narcolepsy, uncontrolled sleep apnea, or other primary sleep disorder judged to be likely a major contributor to fatigue * Screening Epsworth Sleepiness Scale score greater than 15 * Uncontrolled hypothyroidism or anemia * Other medical illness judged by the investigator to affect the participant's fatigue complaints including current viral, bacterial, mycobacterial, or fungal infection 2. MS Disease Activity and Treatment: * Clinical exacerbations within 2 weeks prior to screening visit * Corticosteroid use within 4 weeks prior to screening visit * Beta-interferon, glatiramer acetate, immunosuppressant drugs (mitoxantrone, azathioprine, etc.) are permitted if a stable dose has been used for greater than or equal to 4 weeks and there is no temporal association of drug administration with perceived fatigue; elective on-study dose/regimen changes are not permitted 3. Current or Recent Fatigue Therapy and Other Medications: * Use of more than two doses of ASA (aspirin) greater than 81 mg/d within 2 weeks of screening visit * Use of MS fatigue medications within 2 weeks of screening visit (including amantadine or Central Nervous System stimulants such as modafinil, methylphenidate, and pemoline) * Symptomatic medications (antidepressants, anti-spasticity agents, non-narcotic analgesics) are permitted if a stable dose has been used for \>4 weeks prior to screening for antidepressants and \>2 weeks prior to screening for other symptomatic therapies and there is no temporal association of drug administration with perceived fatigue; elective on-study dose changes are not permitted. * Current use of acetazolamide, antiplatelet agents or anticoagulants, COX-2 inhibitors, methotrexate, oral hypoglycemic medications 4. Medical Contraindications to ASA use: * Allergy to ASA or Non-Steroidal Anti-Inflammatory drugs * Syndrome of asthma, rhinitis and nasal polyps * History of confirmed peptic ulcer or gastrointestinal or severe gynecological bleeding 5. General Health Concerns: * Significant uncontrolled disease of cardiovascular, pulmonary, hepatic, renal, endocrine, rheumatological, neurological, gynecological, or gastrointestinal systems * Pregnancy or unwillingness to utilize contraception * History of alcohol or drug abuse within 6 months of screening or current alcohol intake \>3 drinks/day 6. Laboratory Exclusions (available values obtained within 8 weeks prior to screening visit are acceptable for all except the pregnancy test) * Positive pregnancy test * Hemoglobin less than 11.0 g/dL (women) or 13.0 g/dL (men) * Platelet count \< 120, 000/μL * Serum creatinine level \> 1.4 mg/dL (women) or 1.6 mg/dL (men) * Aspartate aminotransferase (AST/SGOT) or alanine aminotransferase (ALT/SGPT) level greater than 2.5 times the upper limit of normal