Multiple Sclerosis Journal - October 2017 - 1520

Multiple Sclerosis Journal 23(11)
two-tailed, with a critical value of 0.05 using SPSS,
version 22.
Results
Study population
Figure 1 shows the trial profile. Of the 925 MS patients
approached between 1st October 2011 and 1st October
2014, 207 were assessed for eligibility and 90 were
included. Primary reasons for not participating were
the lack of severe fatigue (CIS20r fatigue subscale < 35;
44%) or suspected mood disorders (HADS subscale
depression > 11; 20%). Table 1 shows the baseline characteristics of the study sample. Despite the random
allocation, the aerobic training group had a lower
EDSS score (MD (standard error (SE)),−0.6 (0.3),
p = 0.038), shorter time since diagnosis (−3.7 (1.5),
p = 0.016), lower mean age (−5.1 (2.0), p = 0.014) and
less perceived restrictions in the work/education
domain of the IPA (−0.4 (0.2), p = 0.020). The drop-out
rate post-intervention was 15.7% whereas the overall
drop-out rate at 1-year follow-up was 29.2%. Reasons
for drop-out are listed in Figure 1.
Therapy content
The average (±SD) adherence in the experimental
group was 74 ± 25% completed sessions and 71 ± 25%
of prescribed workload at an average intensity of
14.0 ± 2.1 on the 6-20 Borg scale of perceived exertion. Adherence was significantly (p < 0.05) lower in
the second 8-week period (66 ± 30% completed session; 62 ± 31% of prescribed workload) of treatment
in comparison to the first 8-week period (86 ± 14%
completed session; 79 ± 25% of prescribed workload).
In addition, perceived exertion (6-20 Borg scale of
perceived exertion) following each training session
was significantly higher (13.5 ± 2.0 vs 14.8 ± 2.4;
p < 0.05) during the second 8 weeks of training. A total
of 87% of the participants allocated to the control
condition completed all three consultations with the
MS nurse. The self-reported supplemental medical or
allied healthcare consultations were not significantly
different between the two study groups.
Outcome measures
Cohen's Kappa between assessor's guess and actual
allocation was 0.057 (p = 0.593), indicating successful
blinding of the assessor. The mean CIS20r subscale
fatigue score significantly improved from baseline to
4 months by 4.708 (95% CI = 1.003-8.412; p = 0.014;
Table 2) points in favour of aerobic training. This
effect was not sustained during the follow-up
1520

assessment at months 6 and 12 (Table 2; Figure 2). No
significant improvements were found on the various
domains of societal participation. The effect on the
CIS20r fatigue subscale was preceded by an increase
in peak power output between baseline and 2 months
(MD = 11.701, 95% CI = 0.200-23.202; p = 0.048) in
favour of the aerobic training group. However, no significant improvements were found with regard to
VO2peak and/or anaerobic threshold.
With respect to the secondary fatigue measures, from
baseline to 2 months, a significant effect was found on
the MFIS psychosocial subscale (MD = −0.771, 95%
CI = −1.388 to −0.154; p = 0.019) and on the CIS20r
physical activity subscale (MD = −2.181, 95%
CI = −3.855 to −0.507; p = 0.011), in favour of aerobic
training. No such effect was found from baseline to
4 months or during the follow-up phase.
In total, 11 of the 34 participants (32.4%) in the exercise group, who completed the post-intervention
assessment, and 8 out of 38 participants (21.1%) allocated to the control condition showed a clinically
meaningful reduction of eight points or larger on the
CIS20r fatigue subscale leading to an ARR of 0.113
(95% CI = 0.091-0.317) and a NNT of 8.9 (95%
CI = 3.2 to infinite; p > 0.05). Despite imbalances in
disease severity at baseline, the adjusted analyses
including gender and EDSS did not lead to different
results.
Safety
The odds of (self)reporting an MS relapse in patients
with relapsing-remitting MS (N = 65), corrected for
disease severity, was 0.277 (95% CI = 0.097-0.787;
p = 0.016) in favour of aerobic training. The odds of
undergoing steroid treatment related to an MS relapse
in patients with relapsing-remitting MS, corrected for
disease severity, was 0.946 (95% CI = 0.241-3.711;
p = 0.937).
Discussion
To the best of our knowledge, this study is the largest,
single-blind randomized controlled trial specifically
designed and powered to assess the effectiveness of
aerobic training on MS-related fatigue and societal
participation in severely fatigued patients with MS.
We found a small significant post-intervention effect
in favour of aerobic training on our primary outcome,
MS-related fatigue. The odds of reporting an MS
relapse or receiving steroid treatment indicated that
aerobic training is not associated with a higher risk for
MS exacerbations. The limited magnitude (i.e. 4.7
journals.sagepub.com/home/msj
https://journals.sagepub.com/home/msj
Table of Contents for the Digital Edition of Multiple Sclerosis Journal - October 2017
