Multiple Sclerosis Journal - October 2017 - 1543

LE van den Akker, H Beckerman et al.
fatigue. This basic understanding is of interest when
considering the effectiveness of non-pharmacological
treatments. Cognitive behavioral therapy (CBT) for
MS-related fatigue aims to influence the dysfunctional
cognitions, behaviors, and emotions that perpetuate
fatigue. It has been suggested that MS-related fatigue
can be treated and decreased instead of managed and
accepted.9 Therapists will challenge the meaning of
dysfunctional cognitions and aim to change the behavior of patients with MS-related fatigue and emphasize
more realistic cognitions, emotions, and behaviors.8
Together these changes can break the vicious circle of
fatigue.8
A recent meta-analysis concluded that CBT has a
moderately positive short-term effect on MS-related
fatigue.10 However, this effect decreases with cessation of treatment. When the TREFAMS (TREating
FAtigue in patients with MS)-CBT study began, the
only available randomized controlled trial (RCT)
was that of Van Kessel et al.11 While this study
served as an example for the TREFAMS-CBT study,
it had one major limitation: the same therapist provided both the CBT and the relaxation training.11
This increases the risk of contamination between
study groups and limits generalizability to other
clinical settings and to other therapists.
We aimed to assess the effectiveness of CBT in
decreasing fatigue and improving societal participation in patients with MS, compared to MS nurse
consultations. The CBT therapists were certified
psychologists and CBT was compared to standardized control intervention provided by MS nurses.12
Furthermore, the study included an extended 1-year
post-randomization follow-up and only patients with
severe MS-related fatigue were included.
Methods
Study design and participants
The TREFAMS-CBT study (trial registration:
ISRCTN58583714) is part of the TREFAMS-ACE
multi-trial research program designed to study the
effectiveness of aerobic training, CBT, and energy
conservation management in the treatment of
MS-related fatigue. The design of the three individual
trials is identical and has been outlined previously.12
The TREFAMS-ACE study12 was approved by the
Medical Ethics Committee of the VU University
Medical Center. Fonds NutsOhra (grant number
ZonMw 89000005) funded the program. The
Consolidated Standards of Reporting Trials guidelines for non-pharmacological trials (CONSORT
statement) were used to standardize reporting.13
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Participants were recruited in three Dutch centers
(VU University Medical Center in Amsterdam, the
Radboud University Medical Centre, and the St.
Maartenskliniek in Nijmegen), via referral from physicians at regional centers, personal invitation letters,
advertisement via Internet and posters/pamphlets.
Interested patients were invited for an intake interview to provide additional information about the trial
and to test for eligibility. The intake consisted of a
structured medical history taking, a structured physical examination, questionnaires, and a blood draw.
Main eligibility criteria were as follows: (a) definitive
diagnosis of MS, (b) experience of severe fatigue
(CIS20r fatigue ⩾35), (c) be ambulatory (Expanded
Disability Status Scale (EDSS) score ⩽6), (d) no
signs of exacerbation, (e) no clinical depression
(Hospital Anxiety and Depression Scale (HADS
depression) score >11), and (f) no severe comorbid
disorders (medical history taking and results of the
blood draw). Full inclusion criteria are published.12
Prior to inclusion, written informed consent was
obtained from all participants.
Randomization and masking
Randomization was performed using concealed computerized block-wise randomization, stratified by
treatment center. The block size of 8 was disclosed
after finishing all follow-up measurements. An independent investigator, not the assessors, carried out the
randomization and informed the patient and therapist
about the therapy allocation. The assessors were
blinded for the treatment, and patients and therapists
were instructed not to unblind the assessors. The analyses were performed blinded to participant treatment
allocation.
Procedures
The treatment procedure began in December 2011
and ended in December 2014. A more detailed
description (completed TIDieR (template for intervention description and replication) checklist) of
the CBT intervention and the control intervention
is available in Supplementary Appendix 1 and
Supplementary Appendix 2.1,2
The patients randomly allocated to the CBT received
12 sessions of individual face-to-face therapy spread
over a 4-month period (8 sessions in the first 2 months,
4 sessions in the last 2 months). The CBT protocol
consists of 10 modules: formulating goals, regulating
sleep/wake pattern, changing beliefs regarding MS,
changing beliefs regarding fatigue, reduce the focus
on fatigue, regulation of physical, social, and mental
activity, addressing the role of the environment, and
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Table of Contents for the Digital Edition of Multiple Sclerosis Journal - October 2017
