Table 3.
Study characteristics of included randomized and non-randomized controlled trials
| Author, year |
Study population N (f/m), MS phenotype (R/S/P), Age (y), EDSS, DD (y) |
AAN Class |
MS-specific outcome (primary/secondary) |
Intervention | Interaction effects | Risk of biasd | |
|---|---|---|---|---|---|---|---|
| Randomized controlled trials | |||||||
| Bjarnadottir, 2007 | IG | CG (passive) | III | EDSS (NR) | 5 weeks 3x/week 60 min session progressive cycling (15-20 min) at ~ 55% VO2peak and progressive resistance exercise (13 exercises) | n.s | 2–2–2 |
| 6 (3/3), R, 38.7 y, EDSS 2.1, DD 8.7 y | 10 (8/2), R, 36.1 y, EDSS 1.8, DD 8.3 y | ||||||
| De Oliveira, 2016 | IG | CG (waitlist) | II | EDSS (NR) | 24 weeks 1x/week 60 min Yoga | n.s | 3–3–0 |
| 6 (6/0), NR, 46 y (8), EDSS 3.2 (1.2), DD NR | 6 (5/1), NR, 45 y (9), EDSS 3.1 (1.9), DD NR | ||||||
| Feys, 2019 | IG | CG (waitlist) | III | Total and region-specific brain volume (secondary) | 12 weeks 3x/week (min NR) progressive running | ↑ left pallidum volume | 1–4–1 |
| 21 (20/1), NR, 36.6 y (8.5), EDSS NR, DD 8.1 y (6.1) | 21 (18/3), NR, 44.4 y (8.5), EDSS NR, DD 9.2 y (5.3) | ||||||
| Golzari, 2010 | IG | CG (passive) | III | EDSS (NR) | 8 weeks (24 sessions, min NR) progressive combined stretching, aerobic and resistance exercises | No interaction effects assessed | 0–5–1 |
| 10 (10/0), R, 32.15 y (7.57), EDSS 2.14 (1.06), DD NR | 10 (10/0), R, 33.75 y (8.18), EDSS 1.95 (1.06), DD NR | ||||||
| Grazioli, 2019 | IG | CG (usual care) | III | EDSS (secondary) | 24 weeks 2x/week 60 min combined cycling at 65% HRmax and strength training at 50% 1RM | n.s | 4–2–0 |
| 10 (7/3), NR, 45.91 y (12.09), EDSS 4.73 (.9), DD NR | 10 (8/2), NR, 39.40 y (10.26), EDSS 4.40 (2.26), DD NR | ||||||
| Hoang, 2016 | IG | CG (passive) | II | MSFC (secondary) | 12 weeks 2x/week 30 min interactive exergaming (step training) | ↑ MSFC | 5–0–1 |
| 28 (21/7), R/S/P, 53.4 y (10.7), EDSS 4.1 (1.4), DD NR | 22 (17/5), R/S/P, 51.4 y (12.8), EDSS 4.2 (1.2), DD NR | ||||||
| Kjølhede, 2018e | IG | CG (Waitlist) | II | Total and region-specific brain volume, lesion load, cortical thickness, PBVC, MSFC (NR) | 24 weeks 2x/week (min NR) progressive machine-based resistance training | ↑ relative cortical thickness, MSFC | 5–0–1 |
| 18 (NR) | 17 (NR) | ||||||
| R, 43 y (8), EDSS 2.9 (0.2), DD 7 y (7) | |||||||
| Langeskov-Christensen, 2021 | IG | CG (waitlist) | II | PBVC (primary), volumes of various brain regions, upper spinal cord volume cortical thickness, T2 and black hole lesion load, relapse rate | 24 weeks 2x/week 30–60 min progressive aerobic exercise at 65–95% HRmax | ↓ annualized relapses | 5–0–1 |
| 43 (26/17), R/S/P, 44 y (9.5), EDSS 2.7 (1.4), DD 10.9 y (7.9) | 43 (26/17), R/S/P, 45.6 y (9.3), EDSS 2.8 (1.6), DD 8.6 y (6) | ||||||
| Miller, 2011 | IG | CG (usual care) | II | EDSS (secondary) | 8 weeks 2x/week 60 min task-specific physiotherapy (strength exercises for upper and lower body) | n.s | 5–1–0 |
| 15 (11/4), S/P, 56.3 y (9.0), EDSS 7 (0.5), DD 13 y (9.1) | 15 (8/7), S/P, 52.9 y (6.3), EDSS 7.1 (0.8), DD 18.7 y (8.1) | ||||||
| Moradi, 2015 | IG | CG (passive) | III | EDSS (NR) | 8 weeks 3x/week (min NR) progressive machine-based resistance training at 50–80% 1RM | ↓ EDSS | 5–1–0 |
| 8 (0/8), R/S, 34.38 (11.07) y, EDSS 3 (1–6)a, DD 8.12 y (4.79) | 10 (0/10), R/S, 33.13 (7.08) y, EDSS 3 (1–5)a, DD 6.5 y (5.78) | ||||||
| Petajan, 1996 | IG | CG (waitlist) | III | EDSS (NR) | 15 weeks 3x/week 40 min progressive combined arm/leg ergometry at 60% VO2max | n.s | 3–3–0 |
| 21 (15/6), NR, 41.1 y (2), EDSS 3.8 (0.3), DD 9.3 y (1.6) | 25 (16/9), NR, 39 y (1.7), EDSS 2.9 (0.3), DD 6.2 y (1.1) | ||||||
| Romberg, 2005 | IG | CG (waitlist) | III | MSFC, EDSS (NR) | 26 weeks 3-4x/week (min NR) progressive aerobic (1x/week) and resistance exercise (2-3x/week) | ↑ MSFC | 2–2–2 |
| 47 (30/17), NR, 43.8 y (6.3), EDSS 2 (1.5–3.5)b, DD 6 y (6.5) | 48 (31/17), NR, 43.9 y (7.1), EDSS 2.5 (2–3.5)b, DD 5.5 y (6.4) | ||||||
| Sangelaji, 2014 | IG | CG (waitlist) | III | EDSS (NR) | 10 weeks 3x/week 60–90 min progressive combined cycling, running, resistance and balance exercises | n.s | 2–3–1 |
| 39 (24/15), NR, 33.05 y (7.68), EDSS NR, DD NR | 22 (15/7), NR, 32.05 y (6.35), EDSS NR, DD NR | ||||||
| Controlled trials | |||||||
| Niwald, 2017 | IG | CG (NR) | III | EDSS (NR) | 4 weeks 5x/week (3 × 10 min/day) progressive cycling | n.s | n.a |
| 21 (13/8), NR, 57.19 y (7.62), EDSS 5–6.5c, DD 13.9 y (11.45) | 32 (21/11), NR, 59.7 y (4.2), EDSS 5–6.5c, DD 12.2 y (2.6) | ||||||
| Rasova, 2006 |
Group 1: 24, NR, NR, EDSS 4.10, DD NR Group 2: 36, NR, NR, EDSS 2.21, DD NR Group 3: 19, NR, NR, EDSS 3.42, DD NR |
Group 4 (passive) 16, NR, NR, EDSS 2.32, DD NR | III | EDSS (NR) |
Group 1: 8 weeks 2x/week 60 min neurophysiologically based physiotherapy Group 2: 8 weeks 2x/week 2-30 min progressive cycling at ~ 60% VO2max Group 3: combined program of group 1 and 2 |
↓ EDSS (Group 1, 2, and 3 vs. 4) | n.a |
Data presented as mean (SD) unless otherwise noted. ↑: increased, ↓: decreased
AAN American Academy of Neurology, CG control group, DD disease duration, EDSS Expanded Disability Status Scale, f female, HRmax maximum heart rate, IG intervention group, m male, MS multiple sclerosis, MSFC multiple sclerosis functional composite, n.a. not applicable, n.s. not significant, NR not reported, P primary progressive MS, PBVC percentage brain volume change, R relapsing–remitting MS, RM repetition maximum, RSFC resting-state functional connectivity, S secondary progressive MS, VO2peak/max peak/maximum oxygen consumption, y years
aMedian (range)
bMedian (IQR)
cRange
dLeft score: “low risk of bias”; middle score: “unclear”; right score: “high risk of bias”
eReferred to as crossover design by the study authors. Due to design issues, results are only partially considered here