Kees Okkersen1, Cecilia Jimenez-Moreno2, Stephan Wenninger3, Ferroudja Daidj4, Jeffrey Glennon5, Sarah Cumming6, Roberta Littleford7, Darren G Monckton6, Hanns Lochmüller8, Michael Catt9, Catharina G Faber10, Adrian Hapca7, Peter T Donnan7, Gráinne Gorman11, Guillaume Bassez4, Benedikt Schoser3, Hans Knoop12, Shaun Treweek13, Baziel G M van Engelen14. 1. Department of Neurology, Donders Institute for Brain Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, Netherlands. Electronic address: kees.okkersen@radboudumc.nl. 2. Institute of Genetic Medicine, University of Newcastle, Newcastle, UK. 3. Friedrich-Baur-Institute, Department of Neurology, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany. 4. Neuromuscular Reference Centre, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France. 5. Department of Cognitive Neuroscience, Donders Institute for Brain Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, Netherlands. 6. Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. 7. Tayside Clinical Trials Unit, University of Dundee, Dundee, UK. 8. Institute of Genetic Medicine, University of Newcastle, Newcastle, UK; Department of Neuropediatrics and Muscle Disorders, Medical Center, University of Freiburg, Faculty of Medicine, Freiburg, Germany; Centro Nacional de Análisis Genómico, Center for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Catalonia, Spain. 9. National Innovation Centre for Ageing, University of Newcastle, Newcastle, UK; Catt-Sci, Wellingborough, UK. 10. Department of Neurology, Maastricht University Medical Centre, Maastricht, Netherlands. 11. Institute of Neuroscience, University of Newcastle, Newcastle, UK. 12. Academic Medical Center, University of Amsterdam, Department of Medical Psychology, Amsterdam Public Health Research Institute, Amsterdam, Netherlands. 13. Health Services Research Unit, University of Aberdeen, Aberdeen, UK. 14. Department of Neurology, Donders Institute for Brain Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, Netherlands.
Abstract
BACKGROUND: Myotonic dystrophy type 1 is the most common form of muscular dystrophy in adults and leads to severe fatigue, substantial physical functional impairment, and restricted social participation. In this study, we aimed to determine whether cognitive behavioural therapy optionally combined with graded exercise compared with standard care alone improved the health status of patients with myotonic dystrophy type 1. METHODS: We did a multicentre, single-blind, randomised trial, at four neuromuscular referral centres with experience in treating patients with myotonic dystrophy type 1 located in Paris (France), Munich (Germany), Nijmegen (Netherlands), and Newcastle (UK). Eligible participants were patients aged 18 years and older with a confirmed genetic diagnosis of myotonic dystrophy type 1, who were severely fatigued (ie, a score of ≥35 on the checklist-individual strength, subscale fatigue). We randomly assigned participants (1:1) to either cognitive behavioural therapy plus standard care and optional graded exercise or standard care alone. Randomisation was done via a central web-based system, stratified by study site. Cognitive behavioural therapy focused on addressing reduced patient initiative, increasing physical activity, optimising social interaction, regulating sleep-wake patterns, coping with pain, and addressing beliefs about fatigue and myotonic dystrophy type 1. Cognitive behavioural therapy was delivered over a 10-month period in 10-14 sessions. A graded exercise module could be added to cognitive behavioural therapy in Nijmegen and Newcastle. The primary outcome was the 10-month change from baseline in scores on the DM1-Activ-c scale, a measure of capacity for activity and social participation (score range 0-100). Statistical analysis of the primary outcome included all participants for whom data were available, using mixed-effects linear regression models with baseline scores as a covariate. Safety data were presented as descriptives. This trial is registered with ClinicalTrials.gov, number NCT02118779. FINDINGS: Between April 2, 2014, and May 29, 2015, we randomly assigned 255 patients to treatment: 128 tocognitive behavioural therapy plus standard care and 127 to standard care alone. 33 (26%) of 128 assigned to cognitive behavioural therapy also received the graded exercise module. Follow-up continued until Oct 17, 2016. The DM1-Activ-c score increased from a mean (SD) of 61·22 (17·35) points at baseline to 63·92 (17·41) at month 10 in the cognitive behavioural therapy group (adjusted mean difference 1·53, 95% CI -0·14 to 3·20), and decreased from 63·00 (17·35) to 60·79 (18·49) in the standard care group (-2·02, -4·02 to -0·01), with a mean difference between groups of 3·27 points (95% CI 0·93 to 5·62, p=0·007). 244 adverse events occurred in 65 (51%) patients in the cognitive behavioural therapy group and 155 in 63 (50%) patients in the standard care alone group, the most common of which were falls (155 events in 40 [31%] patients in the cognitive behavioural therapy group and 71 in 33 [26%] patients in the standard care alone group). 24 serious adverse events were recorded in 19 (15%) patients in the cognitive behavioural therapy group and 23 in 15 (12%) patients in the standard care alone group, the most common of which were gastrointestinal and cardiac. INTERPRETATION:Cognitive behavioural therapy increased the capacity for activity and social participation in patients with myotonic dystrophy type 1 at 10 months. With no curative treatment and few symptomatic treatments, cognitive behavioural therapy could be considered for use in severely fatigued patients with myotonic dystrophy type 1. FUNDING: The European Union Seventh Framework Programme.
RCT Entities:
BACKGROUND:Myotonic dystrophy type 1 is the most common form of muscular dystrophy in adults and leads to severe fatigue, substantial physical functional impairment, and restricted social participation. In this study, we aimed to determine whether cognitive behavioural therapy optionally combined with graded exercise compared with standard care alone improved the health status of patients with myotonic dystrophy type 1. METHODS: We did a multicentre, single-blind, randomised trial, at four neuromuscular referral centres with experience in treating patients with myotonic dystrophy type 1 located in Paris (France), Munich (Germany), Nijmegen (Netherlands), and Newcastle (UK). Eligible participants were patients aged 18 years and older with a confirmed genetic diagnosis of myotonic dystrophy type 1, who were severely fatigued (ie, a score of ≥35 on the checklist-individual strength, subscale fatigue). We randomly assigned participants (1:1) to either cognitive behavioural therapy plus standard care and optional graded exercise or standard care alone. Randomisation was done via a central web-based system, stratified by study site. Cognitive behavioural therapy focused on addressing reduced patient initiative, increasing physical activity, optimising social interaction, regulating sleep-wake patterns, coping with pain, and addressing beliefs about fatigue and myotonic dystrophy type 1. Cognitive behavioural therapy was delivered over a 10-month period in 10-14 sessions. A graded exercise module could be added to cognitive behavioural therapy in Nijmegen and Newcastle. The primary outcome was the 10-month change from baseline in scores on the DM1-Activ-c scale, a measure of capacity for activity and social participation (score range 0-100). Statistical analysis of the primary outcome included all participants for whom data were available, using mixed-effects linear regression models with baseline scores as a covariate. Safety data were presented as descriptives. This trial is registered with ClinicalTrials.gov, number NCT02118779. FINDINGS: Between April 2, 2014, and May 29, 2015, we randomly assigned 255 patients to treatment: 128 to cognitive behavioural therapy plus standard care and 127 to standard care alone. 33 (26%) of 128 assigned to cognitive behavioural therapy also received the graded exercise module. Follow-up continued until Oct 17, 2016. The DM1-Activ-c score increased from a mean (SD) of 61·22 (17·35) points at baseline to 63·92 (17·41) at month 10 in the cognitive behavioural therapy group (adjusted mean difference 1·53, 95% CI -0·14 to 3·20), and decreased from 63·00 (17·35) to 60·79 (18·49) in the standard care group (-2·02, -4·02 to -0·01), with a mean difference between groups of 3·27 points (95% CI 0·93 to 5·62, p=0·007). 244 adverse events occurred in 65 (51%) patients in the cognitive behavioural therapy group and 155 in 63 (50%) patients in the standard care alone group, the most common of which were falls (155 events in 40 [31%] patients in the cognitive behavioural therapy group and 71 in 33 [26%] patients in the standard care alone group). 24 serious adverse events were recorded in 19 (15%) patients in the cognitive behavioural therapy group and 23 in 15 (12%) patients in the standard care alone group, the most common of which were gastrointestinal and cardiac. INTERPRETATION: Cognitive behavioural therapy increased the capacity for activity and social participation in patients with myotonic dystrophy type 1 at 10 months. With no curative treatment and few symptomatic treatments, cognitive behavioural therapy could be considered for use in severely fatiguedpatients with myotonic dystrophy type 1. FUNDING: The European Union Seventh Framework Programme.
Authors: Maud van Dorst; Kees Okkersen; Roy P C Kessels; Frederick J A Meijer; Darren G Monckton; Baziel G M van Engelen; Anil M Tuladhar; Joost Raaphorst Journal: Neuroimage Clin Date: 2018-11-28 Impact factor: 4.881
Authors: Sarah A Cumming; Cecilia Jimenez-Moreno; Kees Okkersen; Stephan Wenninger; Ferroudja Daidj; Fiona Hogarth; Roberta Littleford; Gráinne Gorman; Guillaume Bassez; Benedikt Schoser; Hanns Lochmüller; Baziel G M van Engelen; Darren G Monckton Journal: Neurology Date: 2019-08-08 Impact factor: 9.910
Authors: Jacob N Miller; Alison Kruger; David J Moser; Laurie Gutmann; Ellen van der Plas; Timothy R Koscik; Sarah A Cumming; Darren G Monckton; Peggy C Nopoulos Journal: Front Neurol Date: 2021-07-01 Impact factor: 4.003
Authors: Jacob N Miller; Ellen van der Plas; Mark Hamilton; Timothy R Koscik; Laurie Gutmann; Sarah A Cumming; Darren G Monckton; Peggy C Nopoulos Journal: Neurol Genet Date: 2020-08-12