EGAGenomicsPeter-Bram 't Hoenhttps://ega-archive.org/dacs/EGAC00001002434EGAEGA DAC EGAC00001002434EGApeter-bram.thoen@radboudumc.nl<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Findings</h4>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.<h4>Interpretation</h4>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.<h4>Funding</h4>The European Union Seventh Framework Programme.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 K, Jimenez-Moreno Cecilia C, Wenninger Stephan S, Daidj Ferroudja F, Glennon Jeffrey J, Cumming Sarah S, Littleford Roberta R, Monckton Darren G DG, Lochmüller Hanns H, Catt Michael M, Faber Catharina G CG, Hapca Adrian A, Donnan Peter T PT, Gorman Gráinne G, Bassez Guillaume G, Schoser Benedikt B, Knoop Hans H, Treweek Shaun S, van Engelen Baziel G M BGMCommittee., AccessTherapy, clinical_trial, SINGLE, Tired, Clinical Trials, Exercise, dystrophia myotonica 1, Blinding, Clinical Trials., Steinert's disease, Masking, Client, clinical trial, dystrophia myotonica type 1, Trial, Optional, Clinical Trial, Fatigue, Rehabilitation Exercise, Remedial, Blinded, Rehabilitation, Exercise Therapies, Single Person, DM1, myotonic dystrophy 1, blinding, CBT, Steinert myotonic dystrophy, Remedial Exercise, Tiredness, Myotonic dystrophy type 1, Weariness, Lassitude, Blind, masking, Patient, Only, Unspecified, Clients, Remedial Exercises, Therapies, Solitary, Single, Rehabilitation Exercises, Exercises, Steinert disease, MD1, Severe, Alonefbwd4, l(2)04454, DmelCG1772, dac, CIB1, Recognition., shsf3, shfm3, E(Sev-CycE)2B, p21[dacapo], Fbw4, FBW4, dactylin, E130112M23Rik, Dach, CDKN2B, cdi4, SHFM3, Dac, DAC, p27[Dap], dactylyn, dacapo/cyclin-dependent kinase interactor 4, AI182278, p21, CG1772, FBWD4, Dap, Cdi4, CDI4, CES5A1, p27, P15, fbw4, SHSF3, DecapoHeart, Forms, Common Markets, Gatekeepers, Referrals, year, PLXN2, Clinical Trials, Physical, YEAR, dystrophia myotonica 1, Digestive System Finding, Gastrointestinal Organ System, Masking, Diagnosis, TALL-2, Adverse Event Associated with the Gastrointestinal System, Status, Assigned, Clinical Trial, Motor, AE, Compared, Physical Exercises, Method, Eligible, Cultural, symptoms, Falls, HEART, Muscular dystrophy NOS, Experience, Hereditary progressive muscular dystrophy NOS, Muscular Dystrophies, Transfer, Acute Exercises, adult, study_site, cardiac, European Common Market, treatment, Log-Linear Models, Aerobic Exercises, BG, Motor Activities, Physical Restraint, Physical Activity, 74/76, plant peltate hair, Accidental Fall, Economic Community, result, TRDL-1, Weights, Comparison, Aches, Tiredness, procedures, Myotonic dystrophy type 1, {EVENTS}, Based, Bulgaria, Did, DID, Nighttime Sleep, DM[[O]], Social, a, set, decreased, Consultation and Referral, Presentation, Study Site, D5, 2459, Year, Better, Delta, severe, Lam(Dm0), Assign, Combined, Borg Category-Ratio 10 Perceived Exertion Score 5, Diagnose, Participation, digestive system, screening, Eligibility, HexA, no evidence of disease, Communities, Crushing Pains, Parkin-interacting substrate, DM, Difference, CONTINUOUS, SSP29, assessment, familial, ClinicalTrials.gov, Linear Model, Steinert's disease, Curative, Procedure, Diagnoses, Ache, Optional, Cultural Background, Interaction, Dm0, Level of Health, Postmortem, Pains, Dm2, Cultures, Dm1, Dm, Do, BGR, Interpretation, European, Market, About, jf27, CG6944, numerical data, month, diapause, Confirmed, finances, Dm[[2]], Adapt, Aerobic Exercise, Physical Assessment, misg, Hospital Referrals, DmO, DM1, Cultural Beliefs, Model System, Investigative Site, myotonic dystrophy 1, follow up, lamDm[[0]], 2310026N09Rik, European Atomic Energy Community, signs, salaries, Progressive muscular dystrophy, Severely, Methodological, Myodystrophicas, Weariness, Present, Radiating, Activities, Blind, Gatekeeper, GI, DMK, Dmo, primary tumor, Investigator Site, Linear, Physical Suffering, Linear Regression, financial management, Passive Double Immunodiffusion, Falling, Plxn2, Delivery, Elderly, Community, Interpretation of Laboratory Test, Burning Pain, OCT, Lam[[Dm0]], HK, Restricted, Impairment, Myodystrophy, RECEIVING, Effects, Australia-Modified Karnofsky Performance Status 100, Common Market, Tired, years, peltate hair, Assignment, number, General Health, Symptomatic Therapy, Kingdom of the Netherlands, Exercise Training, Hospital Referral, Radiating Pain, Fall and Slip, Determine, Available, model, Sufferings, ZTNF2, CG7826, BULGARIA, Adjustment, Cardiac, Dm(0), Citizenship, It improved, Adjusted, physical_exam, Social Functionings, CG7835, Screening, CG42273, Dm[[0]], Antemortem, Log-Linear, PHYSICAL EXAMINATION, Technique, Suffering, Health Status, Transport, Backgrounds, Modification, anatomical systems, A proliferation-inducing ligand, World Wide Web, TNF-related death ligand 1, BETTER/IMPROVED/RECOVERING, l(2)gdh-7, Cultural Relativisms, 2810428A13Rik, Events, Diagnoses and Examinations, Cured, Muscular Dystrophy, European Communities, General Health Level, outcome, Adverse Events, DmelCG3001, Study, Health Service, Serious Adverse Events Domain, Delivered, Unspecified, Customs, Approximately, WWW, Receive, constitutitional genetic, LAM, MD1, Dystrophy, Dm[[1]], Antemortem Diagnoses, fees, SINGLE, Adapted, use, findings, grupo, European Common Markets, CURATIVE, Result, Regressions, Social Functioning, General Health Status, Registration, Primary, Digestive System, Cultural Backgrounds, lam, Assigned Value, TALL2, CD256, Trdl1, Availability, mo, l(2)04643, Received, Fatigue, Confirmatory, Dystrophies, April, Dm[[o]], Acute Exercise, Overall Health Status, background, scales, Gastrointestinal System, Gastrointestinal System Finding, Single Person, Modified, Treated, Tall2, l(2)jf27, underdeveloped, ensemble, de-identification, Locomotor Activities, increased number, Engagement, Neuromuscular, Consultation, Changed, CG3001, One Hundred, Euratom, lamDm0, Exercise Trainings, ME-IV, APRIL, HERED PROG MUSC DYSTRPHY, Napping, Acute, Lansky Performance Status 100, lethargus, Primary Cause of Death, PARIS, Wake, Restriction, 100, Opinions, Relativisms, Solitary, MDPK, Functionings, Relativism, HEX-A, Cultural Relativism, hereditary, Double Immunodiffusion, General activity, Serious Adverse Events, Severe, physical exam, Health Levels, Alone, Adverse Event Domain, Registered, Overall, clinical_trial, Safeties, European Economic Community, MONTH, DmelCG6944, scale tissue, Presented, Antemortem Diagnosis, Activity, Approximate, cure, Motor Activity, Awaken, Physical Exam, DmLamin, MONTHS, Severe Exertion, Month, muscular dystrophy, Blinding, dormancy, Splitting Pain, Overall Health, Measure, LamDm[[0]], dystrophia myotonica type 1, Second Opinions, Trial, Techniques, Background, Presenting, Body System, Myodystrophica, European Coal and Steel Community, Migratory, Effect, present in fewer numbers in organism, DmelCG42273, European Economic, increased, INTP, Continuous, lamin Dm0, INTERPRETATION, Determination, IMPROVED, SA, Union, hypoplasia, min, GASTROINTESTINAL, Transfer Technique, nlam, General Examination, Hereditary progressive muscular dystrophy, Occurred, genetic, Cure, Methodological Studies, PMD - Progressive muscular dystrophy, CDISC Events Class, disease management, Therapies, Organ System, Lamin Dm[[0]], Event Unit, StudySite, Outcome, Exercises, mKIAA0463, Symptomatic, PHYSICAL EXAM, Registering, Therapy, Constraint, PlexA2, Primary Tumor, Determined, Severe Dysplasia, statistics and numerical data, no complaints, Currently has symptoms, Dmel_CG7826, Aerobic, Limitation, Physical Sufferings, Republic of Bulgaria, Accidental, clinical trial, Deliver, lamin, Years, Menstruation, Crushing Pain, Screenings, AW457381, Primary Neoplasm, Consultations, Examinations and Diagnoses, Awake, Continuing, Common, YEARS, gastrointestinal, PRCDTH, Slip and Fall, Health Service Gatekeepers, Postmortem Diagnosis, General, Does, Adults, Physical Exercise, Karnofsky Performance Status 100, Confirmation, Dmel_CG7835, Hex-A:B, Mnb, MNB, Diagnoses and Examination, Postmortem Diagnoses, GASTROINTESTINAL SYSTEM, European Economic Communities, Continue, blinding, Pain, Steinert myotonic dystrophy, common, Is_Symptomatic, General Health Levels, Seventh., Impaired, Splitting Pains, Improved, Methodological Study, Saint Pierre and Miquelon, Treatments, Health, Radiating Pains, Patient, Took Place, Base, Burning, Adverse Event Associated with Gastrointestinal, St. Pierre and Miquelon, inherited genetic, Measures and Weights, impairment, Physical Examination, Levels, Muscular, HEX, Hex, accessory, Gruppe, Take Place, Gastrointestinal Body System, Procedures, 100: Normal, Gastrointestinal, Social Engagement, Training, Isometric, Migratory Pains, Capacity, Symptomatic Presentation, Compare, Continued, Locomotor, presence, supernumerary, DM1PK, Added, ONGO, reduced, Happen, utilization, subnumerary, Care, Miquelon and St. Pierre, Studies, DOUBLE IMMUNODIFFUSION, Mass, Checklists, symptomatic, Blinded, Web, tiny, Level, Models, registration, Module, primary, Site, putative HLA-DR-associated protein I-2, Wake Up, study, Opinion, Modeling System, Gastroenteral, Occur, Ouchterlony Double Immunodiffusion, cope, Measures, Locomotor Activity, financing, decreased number, Coping, Lassitude, Miquelon and Saint Pierre, masking, funding, PHYSICAL, Symptomatic Treatment, ONGOING, Happened, grupos, Clients, Continual, Splitting, Burning Pains, Congenital muscular dystrophy, Referral, study site, Model, Economic Communities, statistical analysis, small, Myodystrophies, Deidentification, MT-PK, EVENTS, DYRK1, physical examination, Muscular dystrophy (disorder), Functioning, Dm[[mit]], RECEIVED, Performance Status 100, Log Linear Models, Exercise, l(2)25Ec, Hospital, Client, AA589422, Examination and Diagnoses, LamDm[[o]], group, EEC, count in organism, Linear Regressions, Months, TNF- and APOL-related leukocyte expressed ligand 2, Period, Mass Screenings, Health Level, Hereditary progressive muscular dystrophy (disorder), Physical or Textual Reference to Actual Test or Parameter, Dyrk1, techniques, Isometric Exercises, Fall, Corsica, Basic, MD - Muscular dystrophy, Log-Linear Model, Crushing, Assessment, scale, Scales, Basis, Rest, Hereditary progressive muscular dystrophy NOS (disorder), CBT, patient, Health Service Gatekeeper, Trainings, Second Opinion, Migratory Pain, introduction, Annum, Isometric Exercise, Holland, European Common, SEVERE, present in greater numbers in organism, l(2)gdh7, cost, Physical Activities, Treating, European Community, Regression, Only, Lam Dm[[0]], PHAPI2, Therapeutic, Change, cardinality, lamin Dm[[0]], Treatment, Second, Single, Clinical Study Site, capacityQuantity, Steinert disease, Ongoing, groupe, Social Citizenship, methodologyfalseOPTIMISTIC DAC for ReCognitIONData Access Committee EGAC00001002434

2025-1-9

EGAC00001002434960629934199EGAS00001005830EGAD00001008383