Table 1 Outcomes for MSTEP Study

Primary Outcome

Exercise capacity

V0_2peak

10% change[32, 55, 56]

Components of Global Outcome

Exercise efficiency: Gross, net and work efficiency

Gross efficiency = work performed / energy expended × 100%, Net efficiency = work performed / energy expended above rest × 100%, and Work efficiency = work performed / energy expended above that in cycling at 0 W × 100% [57].

10% change [58].

Sub-maximal exercise capacity

The Modified Canadian Aerobic Fitness Test (mCAFT) is a multi-stage step-test, simple to use and inexpensive, that assesses sub-maximal aerobic capacity [59].

1 stage [59]

Functional ambulation

Modified 6 Minute Walk Test (M-6MWT) [60]; distance and fatigability index calculated by [the distance walked in the last minute ÷ distance walked in the first minute], with ratio ≥ 1.0 indicating less fatigability; Reliability high (ICC across 3 walks, 0.95).

50 m. [32, 60–64].

Strength

Grip, vertical jump, push-ups, curl-ups [65]

½ SD: jump 5cm; curl ups 5; push ups 3; grip strength 12 [46].

Fatigue symptoms

Unidimensional Fatigue Impact Scale [66]; which is a Rasch validated measure of fatigue modeled from the original and modified versions [60, 67]

Minimum clinically important difference(MCID) 5; ½ SD = 6 [66].

Mood*

Rand-36 MHI subscale [68, 69];

Meaningful change: 10

Global physical function*

Rand-36 PF subscale [68, 69]

Meaningful change = 10

Health perception*

EQ-5D [70–73]

Meaningful change = 10

Quality of life*

Patient Generated Index* [74, 75]

Meaningful change ½ SD = 12.5

Explanatory Variables

Current disability level

PDDS (patient version of EDSS) for all persons [76]

Relapses

Defined as “patient-reported or objectively observed events typical of an acute inflammatory demyelinating event in the CNS, current or historical, with duration of at least 24 hours, in the absence of fever or infection.” [47]; annualized rate over study period

Exercise adherence

Exercise diary (paper, computer version) daily for 3 months, 1 week every 3 months subsequently; accelerometers worn for 1 week every 3 months (see response to reviewers on feasibility of this) ActivPal [77]

Exercise self-efficacy

3 item questionnaire with demonstrated validity and test-retest reliability (>0.85) [78]

Exercise barriers and benefits

The benefits subscale of the Exercise Benefits/Barriers Scale will be used [79] along with 4 indicators for barriers shown to be independent predictors of exercise engagement [21, 44]