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.
- 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.
- 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.
Screening visit: This is the first study visit. You will complete nine brief questionnaires that evaluate your MS-related fatigue, sleep, pain, and overall function. This will take 40-60 minutes. You will also have a review of your fatigue symptoms, brief neurological examination and complete a test of mental concentration called the PASAT. Finally, if you meet study eligibility criteria to this point, you will have blood drawn (about 2 teaspoons) to test for causes of fatigue. If you do not meet all of the entry criteria for the study at this point, then you may be eligible for rescreening at a later date (another attempt to enter the study) at the discretion of the medical doctor.
Baseline visit: About 1-2 weeks after the screening visit, you will return to the clinic to repeat the questionnaires, PASAT, and have blood drawn (about 2 teaspoons). If you are
a woman who can become pregnant, you will have a urine pregnancy test. You will also do arm and leg strength testing in the motor laboratory for about 45 minutes. After this visit, you will be put in one of three groups by chance (like the flip of a coin). One group will receive 1300 milligrams of aspirin daily (equivalent to 4 regular aspirin). The second group will receive 162 milligrams of aspirin daily (equivalent to 2 "baby" aspirin). The third group will receive a placebo ("sugar pill") that does not contain aspirin. The Mayo Clinic Pharmacy in Minnesota will directly mail you the study medication based on the group you are in. You will take the medication every day (2 pills in the morning and 2 pills at noon) for the next 8 weeks. You, your doctor, and the staff that work with you during the study will not know which group you are in during
Week 4 visit: You will return to the clinic to complete the questionnaires, PASAT, motor lab testing, and have your blood drawn (about 1 tablespoon). You will be asked
questions about whether the study medication is helping you and if you notice any side effects.
Week 8 visit: This is the last study visit. You will return to the clinic to complete the questionnaires, PASAT, motor lab testing, and have your blood drawn (about 1
tablespoon). You will be asked questions about whether the study medication is helping you, if you noticed any side effects, and to guess which study group you were in.
During the study, you must not take aspirin, anti-inflammatory medications such as ibuprofen and similar drugs, or blood thinners. You should contact the study physician before beginning any new prescription medications.
Last updated: 01/09/2013
NCT ID: NCT00467584