Cognitive behavioural therapy with optional graded exercise therapy in patients with severe fatigue with myotonic dystrophy type 1

a multicentre, single-blind, randomised trial

Kees Okkersen, Cecilia Jimenez-Moreno, Stephan Wenninger, Ferroudja Daidj, Jeffrey Glennon, Sarah Cumming, Roberta Littleford, Darren G. Monckton, Hanns Lochmüller, Michael Catt, Catharina G. Faber, Adrian Hapca, Peter T. Donnan, Gráinne Gorman, Guillaume Bassez, Benedikt Schoser, Hans Knoop, Shaun Treweek, Baziel G.M. van Engelen, the OPTIMISTIC consortium

Research output: Contribution to journalArticle

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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 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 fatigued patients with myotonic dystrophy type 1.

Funding
The European Union Seventh Framework Programme.
Original languageEnglish
Pages (from-to)671-680
Number of pages10
JournalThe Lancet neurology
Volume17
Issue number8
Early online date19 Jun 2018
DOIs
Publication statusPublished - Aug 2018

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Exercise Therapy
Myotonic Dystrophy
Cognitive Therapy
Fatigue
Social Participation
Exercise
Linear Models
Muscular Dystrophies
Paris
European Union
Therapeutics
Interpersonal Relations
Random Allocation
Checklist
Netherlands
Health Status
France
Germany

Cite this

Cognitive behavioural therapy with optional graded exercise therapy in patients with severe fatigue with myotonic dystrophy type 1 : a multicentre, single-blind, randomised trial. / Okkersen, Kees; Jimenez-Moreno, Cecilia; Wenninger, Stephan; Daidj, Ferroudja; Glennon, Jeffrey; Cumming, Sarah; Littleford, Roberta; Monckton, Darren G.; Lochmüller, Hanns; Catt, Michael; Faber, Catharina G.; Hapca, Adrian; Donnan, Peter T.; Gorman, Gráinne; Bassez, Guillaume; Schoser, Benedikt; Knoop, Hans; Treweek, Shaun; van Engelen, Baziel G.M.; the OPTIMISTIC consortium.

In: The Lancet neurology, Vol. 17, No. 8, 08.2018, p. 671-680.

Research output: Contribution to journalArticle

Okkersen, K, Jimenez-Moreno, C, Wenninger, S, Daidj, F, Glennon, J, Cumming, S, Littleford, R, Monckton, DG, Lochmüller, H, Catt, M, Faber, CG, Hapca, A, Donnan, PT, Gorman, G, Bassez, G, Schoser, B, Knoop, H, Treweek, S, van Engelen, BGM & the OPTIMISTIC consortium 2018, 'Cognitive behavioural therapy with optional graded exercise therapy in patients with severe fatigue with myotonic dystrophy type 1: a multicentre, single-blind, randomised trial', The Lancet neurology, vol. 17, no. 8, pp. 671-680. https://doi.org/10.1016/S1474-4422(18)30203-5
Okkersen, Kees ; Jimenez-Moreno, Cecilia ; Wenninger, Stephan ; Daidj, Ferroudja ; Glennon, Jeffrey ; Cumming, Sarah ; Littleford, Roberta ; Monckton, Darren G. ; Lochmüller, Hanns ; Catt, Michael ; Faber, Catharina G. ; Hapca, Adrian ; Donnan, Peter T. ; Gorman, Gráinne ; Bassez, Guillaume ; Schoser, Benedikt ; Knoop, Hans ; Treweek, Shaun ; van Engelen, Baziel G.M. ; the OPTIMISTIC consortium. / Cognitive behavioural therapy with optional graded exercise therapy in patients with severe fatigue with myotonic dystrophy type 1 : a multicentre, single-blind, randomised trial. In: The Lancet neurology. 2018 ; Vol. 17, No. 8. pp. 671-680.
@article{1fbf3b7e8c7043e49c3e62e98e9abb58,
title = "Cognitive behavioural therapy with optional graded exercise therapy in patients with severe fatigue with myotonic dystrophy type 1: a multicentre, single-blind, randomised trial",
abstract = "BackgroundMyotonic 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.MethodsWe 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.FindingsBetween 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.InterpretationCognitive 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.FundingThe European Union Seventh Framework Programme.",
author = "Kees Okkersen and Cecilia Jimenez-Moreno and Stephan Wenninger and Ferroudja Daidj and Jeffrey Glennon and Sarah Cumming and Roberta Littleford and Monckton, {Darren G.} and Hanns Lochm{\"u}ller and Michael Catt and Faber, {Catharina G.} and Adrian Hapca and Donnan, {Peter T.} and Gr{\'a}inne Gorman and Guillaume Bassez and Benedikt Schoser and Hans Knoop and Shaun Treweek and {van Engelen}, {Baziel G.M.} and {the OPTIMISTIC consortium}",
note = "This study was funded by the European Union Seventh Framework Program, under grant agreement number 305697 (the Observational Prolonged Trial In Myotonic dystrophy type 1 to Improve Quality of Life Standards, a Target Identification Collaboration [OPTIMISTIC] project). We thank Marie Kierkegaard (Karolinska University Hospital, Karolinska Institutet, Department of Physical Therapy, Sweden) and Don MacKenzie (Marigold Foundation, Calgary, AB, Canada) as members of the external advisory board for their continued monitoring and recommendations for improvement of our study. The Health Services Research Unit (University of Aberdeen, Aberdeen, UK) receives core funding from the Chief Scientist Office of the Scottish Government Health Directorates. We acknowledge the contribution to this study made by the Tayside Clinical Trials Unit, University of Dundee (Dundee, UK).",
year = "2018",
month = "8",
doi = "10.1016/S1474-4422(18)30203-5",
language = "English",
volume = "17",
pages = "671--680",
journal = "The Lancet neurology",
issn = "1474-4422",
publisher = "Lancet Publishing Group",
number = "8",

}

TY - JOUR

T1 - Cognitive behavioural therapy with optional graded exercise therapy in patients with severe fatigue with myotonic dystrophy type 1

T2 - a multicentre, single-blind, randomised trial

AU - Okkersen, Kees

AU - Jimenez-Moreno, Cecilia

AU - Wenninger, Stephan

AU - Daidj, Ferroudja

AU - Glennon, Jeffrey

AU - Cumming, Sarah

AU - Littleford, Roberta

AU - Monckton, Darren G.

AU - Lochmüller, Hanns

AU - Catt, Michael

AU - Faber, Catharina G.

AU - Hapca, Adrian

AU - Donnan, Peter T.

AU - Gorman, Gráinne

AU - Bassez, Guillaume

AU - Schoser, Benedikt

AU - Knoop, Hans

AU - Treweek, Shaun

AU - van Engelen, Baziel G.M.

AU - the OPTIMISTIC consortium

N1 - This study was funded by the European Union Seventh Framework Program, under grant agreement number 305697 (the Observational Prolonged Trial In Myotonic dystrophy type 1 to Improve Quality of Life Standards, a Target Identification Collaboration [OPTIMISTIC] project). We thank Marie Kierkegaard (Karolinska University Hospital, Karolinska Institutet, Department of Physical Therapy, Sweden) and Don MacKenzie (Marigold Foundation, Calgary, AB, Canada) as members of the external advisory board for their continued monitoring and recommendations for improvement of our study. The Health Services Research Unit (University of Aberdeen, Aberdeen, UK) receives core funding from the Chief Scientist Office of the Scottish Government Health Directorates. We acknowledge the contribution to this study made by the Tayside Clinical Trials Unit, University of Dundee (Dundee, UK).

PY - 2018/8

Y1 - 2018/8

N2 - BackgroundMyotonic 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.MethodsWe 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.FindingsBetween 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.InterpretationCognitive 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.FundingThe European Union Seventh Framework Programme.

AB - BackgroundMyotonic 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.MethodsWe 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.FindingsBetween 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.InterpretationCognitive 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.FundingThe European Union Seventh Framework Programme.

U2 - 10.1016/S1474-4422(18)30203-5

DO - 10.1016/S1474-4422(18)30203-5

M3 - Article

VL - 17

SP - 671

EP - 680

JO - The Lancet neurology

JF - The Lancet neurology

SN - 1474-4422

IS - 8

ER -