TREating Fatigue in Multiple Sclerosis - Aerobic Training
Background: TREFAMS is an acronym for TReating FAtigue in Multiple Sclerosis, while ACE refers to rehabilitation treatment methods under study, that is, Aerobic training, Cognitive behavioral therapy, and Energy conservation management. The TREFAMS-ACE research program consisted of four studies and had 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/Design: Ambulatory patients (n = 270) suffering from MS-related fatigue were recruited to three single-blinded randomized clinical trials (RCTs). In each RCT, 90 patients were randomly allocated to the trial-specific intervention or to a low-intensity intervention that is the same for all RCTs. This low-intensity intervention consisted of three individual consultations with a specialized MS-nurse. The trial-specific interventions were Aerobic Training, Cognitive Behavioral Therapy, and Energy Conservation Management. These interventions consisted of 12 individual therapist-supervised sessions with additional intervention-specific home exercises. The therapy period lasted 16 weeks. All RCTs had 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 were assessed approximately 1 week prior to, and at 8, 16, 26 and 52 weeks after randomization. The assessors were blinded to allocation. Pro- and anti-inflammatory cytokines in serum, salivary cortisol, physical fitness, physical activity, coping, self-efficacy, illness cognitions and other determinants were longitudinally measured in order to study the neurobiological mechanisms of action.
Discussion: The TREFAMS-ACE program is unique in its aim to assess the effectiveness of three rehabilitation treatments. The program 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 program 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 registrations: Current Controlled Trials ISRCTN69520623, ISRCTN58583714, and ISRCTN82353628
Planning: Study completed; main findings published
- Beckerman et al. The 2-minute walk test is not a valid method to determine aerobic capacity in persons with Multiple Sclerosis. Multiple Sclerosis 25 (7); Conference proceeding (RIMS Annual Meeting 2019)
- Blikman et al. 2019 Energy Conservation Management for People With Multiple Sclerosis–Related Fatigue: Who Benefits? AM J Occ Ther 73 (4)
- Blikman et al. 2018. Physical behaviour is weakly associated with physical fatigue in persons with multiple sclerosis-related fatigue. JRM 50 (9)
- Blikman et al. 2017 Effectiveness of energy conservation management on fatigue and participation in multiple sclerosis: A randomized controlled trial; Mulitple Sclerosis 23 (11)
- Lizanne van den akker et al. 2017 Cognitive Behavioural Therapy positively affects fatigue in patients with multiple sclerosis - results of a randomized clinical trial; Multiple Sclerosis 23 (11)
- Martin Heine et al. 2017 Does Aerobic training alleviate fatigue in and improve societal participation in fatigue patients with multiple sclerosis? A randomized clinical trial; Multiple Sclerosis; 23 (11)
- Lizanne van den Akker et al. The role of appraisal and coping style in relation with societal participation in fatigued patients with multiple sclerosis: a cross-sectional multiple mediator analysis. Journal of Behavioral Medicine 39 (5), 855-865
- Martin Heine et al. 2016 Real-time assessment of fatigue in patients with multiple sclerosis: How does it relate to commonly-used self-report fatigue questionnaires? Archives of Physical Medicine and Rehabilitation 97 (11), 1887 - 1894
- Beckerman et al.; The effectiveness of aerobic training, cognitive behavioural therapy, and energy conservation management in treating MS-related fatigue: the design of the TREFAMS-ACE programme. Trials 2013:14:250
- Heine et al.; Validity of Maximal Exercise Testing in People With Multiple Sclerosis and Low to Moderate Levels of Disability. Physical Therapy 2014:94:08
- Heine et al.; Reliability and responsiveness of cardiopulmonary exercise testing in fatigued persons with multiple sclerosis and low to mild disability. PLoS ONE 10(3): e0122260. doi:10.1371/ journal.pone.0122260
- Heine et al.; Validity of Oxygen Uptake Efficiency Slope in patients with Multiple Sclerosis. J Rehabil Med 2014; 46: 656–661
- Heine et al.; Cardiopulmonary fitness is related to disease severity in multiple sclerosis. Multiple Sclerosis; DOI: 10.1177/ 1352458515581437
PROFESSIONAL PUBLICATIONS (DUTCH)
- Effect conditietraining en gedragstherapie op vermoeidheid bij MS-patiënten; 2013; Wetenschapsmagazine Jeroen Bosch Ziekenhuis
- J. van Meeteren et al.; Effectiviteit van aerobe training, cognitieve gedragstherapie en energiemanagement bij MS-gerelateerde vermoeidheid - TREFAMS-ACE studie; 06/2012; Nederlands Tijdschrift voor Revalidatiegeneeskunde
- M. Miley-Schevenhoven, M.Heine, I. van de Port; TREFAMS-A: Een onderzoek naar de effectiviteit van aerobe training op vermoeidheidsklachten bij Multipele Sclerose; 2011; vakblad NVFG