The purpose of the present study is to test the hypothesis that aerobic training can reduce flu-like symptoms following interferon beta 1a injections in patients with Multiple Sclerosis.

A secondary purpose is to evaluate whether or not changes in circulating cytokines provide a mechanism that can explain a potential positive effect.

Flu-like symptoms (FLS) such as fever, muscle aches, chills, and fatigue are common side effects of interferon beta (IFN-ß) treatment and may affect the willingness of patients with multiple sclerosis (MS) to initiate therapy. The initiation phase of MS treatment is a critical period that can affect patients' views on the long-term acceptability and the adherence to the therapy, underscoring the need for strategies to reduce treatment-related adverse events such as FLS following IFN-ß injections.

Once-weekly intramuscular IFNß-1a, which has been available since 1996, is indicated for the treatment of patients with relapsing forms of MS to slow the accumulation of physical disability progression and the frequency of clinical exacerbations. Although intramuscular IFNß-1a is generally well tolerated, FLS have been reported in up to 76% of patients receiving this treatment. Consequently, interventions that can reduce FLS after IFNß-1a injection are warranted. One approach to reduce FLS has been dose titration. Titration is the practice of initiating therapy with a lower starting dose and gradually increasing the dose at defined intervals until the full dose is reached. Moreover, a combination of dose titration and pre-treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen in healthy subjects, has been sown to reduce FLS severity by 37-76%. However, not all patients benefit from dose titration and also the effects in MS still have to be determined. Consequently, other types of FLS management after IFNß-1a injection have to be determined.

Interestingly, case reports from both Finland and Denmark suggest that aerobic exercise is able to markedly reduce FLS symptoms in MS patients, but so far no studies have evaluated this. However, from healthy subjects it is known that aerobic exercise is capable of positively influencing the immune system and evidence suggests that the prophylactic effect of exercise may, to some extent, be the induction of an anti-inflammatory environment with each bout of exercise (e.g. via increases in circulating anti-inflammatory cytokines including interleukin (IL)-1 receptor antagonist and IL-10).

The existing evidence is particularly suggestive of an acute effect of aerobic exercise on the circulating cytokine levels, which could be an important mechanism in explaining a potential positive effect of aerobic exercise on FLS.

Consequently, the purpose of the present study is to test the hypothesis that aerobic training can reduce FLS following interferon beta 1a injections in patients with Multiple Sclerosis.

A secondary purpose is to evaluate whether or not changes in circulating cytokines provide a mechanism that can explain a potential positive effect.

Inclusion Criteria:

• Definite relapsing-remitting MS according to the McDonald criteria
• Treated with IFNß-1a (Avonex®) for at least 6 months
• Frequent experiencing FLS (muscle aches, chills, fatigue, fewer9) in the hours following IFNß-1a injection (self-reporting that this happens 75% or more of the times after injection).
• Female subjects of childbearing potential are required to practice effective contraception during the study and to continue contraception for 30 days after their last dose of study treatment.
• Expected to be able to complete the aerobic exercise intervention
• Willingly to transport themselves to the exercise/testing facility
• Give informed consent
• Age above 18 years

Exclusion Criteria:

• Have FLS (i.e. muscle aches, chills, fatigue or fewer) or serious infection within a 24h period prior to the screening. Patients having chronic FLS or infection will, therefore, be excluded. This will be tested by patient interview and, if required, further examination
• Have a known history or positive test result for hepatitis B, hepatitis C, or HIV
• Use beta-blockers.
• Have clinically significant abnormality in laboratory or electrocardiogram measures, chronic fatigue syndrome or fibromyalgia, pre-malignant disease, or malignant disease
• Have had allergy shot or desensitization therapy within 1 month of day 1 (randomization) vaccination within 2 weeks of day 1.
• Stop taking IFNß-1a.
• Are pregnant.
• Suffer from dementia, alcohol abuse or have a pacemaker.