This is a protocol for a Cochrane Review (intervention). The objectives are as follows:

Primary objectives

The primary objectives of this review are as follows.

1.1 To determine the immediate (i.e. postintervention; 1.1a) and long-term (i.e. follow-up; 1.1b) benefits of exercise therapy, when compared to a control group, on self-reported fatigue in people with MS; and

1.2 To specifically determine the immediate and long-term benefits of exercise therapy, when compared to a control group, on self-reported fatigue when only clinical trials are considered in which (1.2a) self-reported fatigue was the primary outcome and (1.2b) only people with MS with predefined levels of self-reported fatigue were included.

Secondary objectives

The following secondary objectives will be pursued; each relevant to people with MS, clinicians and academics.

Safety

2.1 To determine the safety of exercise therapy, when compared to a control group, as determined by an exploratory review of reported adverse effects over the course of the intervention phase.

2.2 To confirm the safety of exercise therapy, when compared to a control group, as determined by a confirmatory review of reported MS exacerbations, falls, and overuse injuries over the course of the intervention phase.

Intervention characteristics

3.1 Determine the immediate and long-term differential impact of different exercise therapy modalities on self-reported fatigue (e.g. aerobic training).

3.2 Explore the relationship between dose of exercise therapy (an agglomeration of frequency, time per session, and program duration) and the immediate and long-term benefits of exercise therapy on fatigue.

3.3 Explore the relationship between features of exercise therapy programs (e.g. progression, overload, specificity) and the immediate and long-term benefits of exercise therapy on fatigue.

Participant characteristics

4.1 Determine the impact of baseline fatigue levels on the immediate and long-term benefits of exercise therapy on fatigue.

4.2 Determine the impact of baseline levels of disease severity (i.e. Expanded Disability Status Scale [EDSS]) on the immediate and long-term benefits of exercise therapy on fatigue.

Study design characteristics

5.1 Determine the impact of the specific self-reported fatigue measure (e.g. Fatigue Severity Scale) on the immediate and long-term benefits of exercise therapy on fatigue.

5.2 Determine the impact of methodological quality (i.e. risk of bias) and (self-reported) pilot studies, on the immediate and long-term benefits of exercise therapy on fatigue.

5.3. Determine the impact of the type of control group on the immediate and long-term benefits of exercise therapy on fatigue.