The effectiveness of aerobic training, cognitive behavioural therapy, and energy conservation management in treating MS-related fatigue: the design of the TREFAMS-ACE programmeReport as inadecuate

The effectiveness of aerobic training, cognitive behavioural therapy, and energy conservation management in treating MS-related fatigue: the design of the TREFAMS-ACE programme - Download this document for free, or read online. Document in PDF available to download.


, 14:250

First Online: 12 August 2013Received: 24 January 2013Accepted: 01 August 2013DOI: 10.1186-1745-6215-14-250

Cite this article as: Beckerman, H., Blikman, L.J., Heine, M. et al. Trials 2013 14: 250. doi:10.1186-1745-6215-14-250


BackgroundTREFAMS is an acronym for TReating FAtigue in Multiple Sclerosis, while ACE refers to the rehabilitation treatment methods under study, that is, Aerobic training, Cognitive behavioural therapy, and Energy conservation management. The TREFAMS-ACE research programme consists of four studies and has two main objectives: 1 to assess the effectiveness of three different rehabilitation treatment strategies in reducing fatigue and improving societal participation in patients with MS; and 2 to study the neurobiological mechanisms of action that underlie treatment effects and MS-related fatigue in general.

Methods-DesignAmbulatory patients n = 270 suffering from MS-related fatigue will be recruited to three single-blinded randomised clinical trials RCTs. In each RCT, 90 patients will be randomly allocated to the trial-specific intervention or to a low-intensity intervention that is the same for all RCTs. This low-intensity intervention consists of three individual consultations with a specialised MS-nurse. The trial-specific interventions are Aerobic Training, Cognitive Behavioural Therapy, and Energy Conservation Management. These interventions consist of 12 individual therapist-supervised sessions with additional intervention-specific home exercises. The therapy period lasts 16 weeks. All RCTs have the same design and the same primary outcome measures: fatigue - measured with the Checklist Individual Strength, and participation - measured with the Impact on Participation and Autonomy questionnaire. Outcomes will be assessed 1 week prior to, and at 0, 8, 16, 26 and 52 weeks after randomisation. The assessors will be blinded to allocation. Pro- and anti-inflammatory cytokines in serum, salivary cortisol, physical fitness, physical activity, coping, self-efficacy, illness cognitions and other determinants will be longitudinally measured in order to study the neurobiological mechanisms of action.

DiscussionThe TREFAMS-ACE programme is unique in its aim to assess the effectiveness of three rehabilitation treatments. The programme will provide important insights regarding the most effective treatment for MS-related fatigue and the mechanisms that underlie treatment response. A major strength of the programme is that the design involves three almost identical RCTs, enabling a close comparison of the treatment strategies and a strong overall meta-analysis. The results will also support clinical practice guidelines for the treatment of MS-related fatigue.

Trial registrationsCurrent Controlled Trials ISRCTN69520623, ISRCTN58583714, and ISRCTN82353628

KeywordsMultiple sclerosis Fatigue Aerobic training Energy conservation management Cognitive behavioural therapy Biomarkers HPA-axis Cortisol Cytokines Rehabilitation medicine Randomised controlled trial AbbreviationsATAerobic training

B-IPQBrief Illness perception questionnaire

CBRSQCognitive and behavioural responses to symptoms questionnaire

CBTCognitive behavioural therapy

CIRSCumulative illness rating scale

CIS20rChecklist individual strength

CISSCoping inventory for stressful situations

CNSCentral nervous system

COPMCanadian occupational performance measure

ECMEnergy conservation management

EDSSExpanded disability status scale

FSQFatigue strategies questionnaire

FSSFatigue severity scale

HADSHospital anxiety and depression scale

HPA-axisHypothalamic-pituitary-adrenal axis

IECMIndividual energy conservation management

IESImpact of event scale

ICQIllness cognition questionnaire

IMQIllness management questionnaire

IPAImpact on participation and autonomy

MFISModified fatigue impact scale

MSMultiple sclerosis

OTOccupational therapist

PCSPain catastrophising scale

PRISMPictorial representation of illness measure


RCTRandomised clinical trial

SAESerious adverse events

SES-28Self-efficacy scale 28

SF36Medical outcome study short form 36 items

SIPSickness impact profile

SSLSocial support list

TREFAMS-ACETreating fatigue in multiple sclerosis - aerobic training, cognitive behavioural therapy, energy conservation management

TSHThyroid stimulating hormone

UMCNUniversity medical centre Nijmegen

VO2maxMaximum oxygen consumption

WmaxMaximum work rate.

Electronic supplementary materialThe online version of this article doi:10.1186-1745-6215-14-250 contains supplementary material, which is available to authorized users.

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Author: Heleen Beckerman - Lyan JM Blikman - Martin Heine - Arjan Malekzadeh - Charlotte E Teunissen - Johannes BJ Bussmann - Ger


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