Multiple Sclerosis Journal - October 2017 - 1529

LJM Blikman, J van Meeteren et al.
Table 1. Inclusion and exclusion criteria.
Inclusion criteria

Exclusion criteria

Definitive diagnosis of MS

Depression (Hospital Anxiety and Depression Scale
(HADS) subscale depression >11)
Severe co-morbidity (Cumulative Illness Rating
Scale (CIRS) item scores ⩾3)
Primary sleep disorders
Current pregnancy or having given birth <3 months

Severely fatigued (Checklist Individual Strength
(CIS20r) subscale fatigue ⩾35)
Aged between 18 and 70 years
Ambulant (Expanded Disability Status Scale (EDSS)
score ⩽6.0)
No evident signs of an MS exacerbation or a
corticosteroid treatment <3 months
No infections, anaemia, thyroid dysfunction

Newly initiated pharmacological (e.g. Amantadine)
or non-pharmacological treatment for fatigue (e.g.
ECM, AT, CBT or other) <3 months

MS: multiple sclerosis; ECM: energy conservation management; AT: aerobic training; CBT: cognitive behavioural therapy.
See Beckerman et al.16 for a complete list of all inclusion and exclusion criteria.

treatment centre. An independent investigator carried
out the randomization and informed the patient and
the planning bureau of the allocated treatment.
Patients were explicitly instructed and reminded not
to disclose which treatment they were receiving to the
single-blinded assessor. Furthermore, before analyses, study identification numbers were re-coded (by
the independent researcher) in order to facilitate blind
analyses.

Outcomes
All measurements were carried out 1 week prior to randomization and at 8, 16 (i.e. post-intervention), 26 and
52 weeks after starting the treatment. Outcome measures consisted of validated self-reported questionnaires
and assessor-based interviews. The self-reported questionnaires were offered to participants via Internet or
on paper and were completed at home. The sequence of
the questionnaires was randomized between measurement occasions. The assessor-based interviews were
conducted during the measurement visit to the participating outpatient rehabilitation departments.
Primary outcome measures. Fatigue was measured
with the CIS20r, using the domain subjective experience of fatigue, focussing on the past 2 weeks.17 This
fatigue domain consists of eight items, scored on a
7-point scale, with a total score ranging from 8 to 56,
higher scores reflecting more fatigue. A difference of
8 points on the CIS20r subscale fatigue between the
groups was considered clinically relevant.16,18
Societal participation was assessed with the Impact on
Participation and Autonomy questionnaire (IPA),19
developed to assess the severity of restrictions in participation and autonomy. The IPA addresses perceived
participation, reflected in 32 items in five domains,
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including autonomy indoors, autonomy outdoors,
family role, social relations, and work and education.
Responses to items range from 0 to 4, and for each
domain, a mean item score is calculated; higher scores
indicate greater restrictions in participation and autonomy. A study in a heterogeneous outpatient rehabilitation population, including patients with neuromuscular
disorders, showed that the IPA was moderately able to
detect within-patient improvement over time;20
another study showed similar small to moderate standardized response means of 0.0 up to 0.3.21 However,
no studies have been conducted on the clinimetric
properties of the IPA in individuals with MS.
Secondary outcome measures. Because MS-related
fatigue is a multidimensional phenomenon, several
other fatigue measures were included as secondary
outcomes:
1. The remaining three domains of the CIS20r:
motivation (4 items), physical activity (3 items)
and concentration (5 items); higher scores indicate lower motivation, lower physical activity
and more concentration problems due to fatigue.
2. The Modified Fatigue Impact Scale (MFIS):
total sum score and subscale scores for the
physical, cognitive and psychosocial domain,
higher scores reflect a greater impact of
fatigue.22
3. The Fatigue Severity Scale (FSS) estimates the
severity, frequency and impact of fatigue on
daily life, a higher score indicating more perceived fatigue.23
In addition, the Medical Outcomes Study Short Form
36 (SF-36)24 and the Rehabilitation Activities Profile
(RAP)25 were used to measure daily functioning and
participation on several life domains.
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Table of Contents for the Digital Edition of Multiple Sclerosis Journal - October 2017