Cognitive behaviour therapy plus aerobic exercise training to increase activity in patients with myotonic dystrophy type 1 (DM1) compared to usual care (OPTIMISTIC): study protocol for randomised controlled trial

Baziel van Engelen, OPTIMISTIC Consortium, Shaghayegh Abghari, Armaz Aschrafi, Sacha Bouman, Yvonne Cornelissen, Jeffrey Glennon, Perry Groot, Arend Heerschap, Linda Heskamp, Tom Heskes, Katarzyna Kapusta, Ellen Klerks, Hans Knoop, Daphne Maas, Kees Okkersen, Geert Poelmans, Ridho Rahmadi, Baziel van Engelen, Marlies van Nimwegen, Grainne Gorman, Cecilia Jimenez Moreno, Hanns Lochmüller, Mike Trenell, Sandra van Laar, Libby Wood, Benedikt Schoser, Stephan Wenninger, Angela Schüller, Mrs Rémie Auguston, Lignier Baptiste, Caroline Barau, Guillaume Bassez, Pascale Chevalier, Florence Couppey, Stéphanie Delmas, Jean-François Deux, Celine Dogan, Amira Hamadouche, Karolina Hankiewicz, Laure Lhermet, Lisa Minier, Amandine Rialland, David Schmitz, Darren G Monckton, Sarah A Cumming, Berit Adam, Peter Donnan, Michael Hannah, Fiona Hogarth, Roberta Littleford, Emma McKenzie, Petra Rauchhaus, Erna Wilkie, Jennifer Williamson, Mike Catt, Juliane Dittrich, Ameli Schwalber, Shaun Treweek, Baziel van Engelen, OPTIMISTIC Consortium, Shaghayegh Abghari, Armaz Aschrafi, Sacha Bouman, Yvonne Cornelissen, Jeffrey Glennon, Perry Groot, Arend Heerschap, Linda Heskamp, Tom Heskes, Katarzyna Kapusta, Ellen Klerks, Hans Knoop, Daphne Maas, Kees Okkersen, Geert Poelmans, Ridho Rahmadi, Baziel van Engelen, Marlies van Nimwegen, Grainne Gorman, Cecilia Jimenez Moreno, Hanns Lochmüller, Mike Trenell, Sandra van Laar, Libby Wood, Benedikt Schoser, Stephan Wenninger, Angela Schüller, Mrs Rémie Auguston, Lignier Baptiste, Caroline Barau, Guillaume Bassez, Pascale Chevalier, Florence Couppey, Stéphanie Delmas, Jean-François Deux, Celine Dogan, Amira Hamadouche, Karolina Hankiewicz, Laure Lhermet, Lisa Minier, Amandine Rialland, David Schmitz, Darren G Monckton, Sarah A Cumming, Berit Adam, Peter Donnan, Michael Hannah, Fiona Hogarth, Roberta Littleford, Emma McKenzie, Petra Rauchhaus, Erna Wilkie, Jennifer Williamson, Mike Catt, Juliane Dittrich, Ameli Schwalber, Shaun Treweek

Abstract

Background: Myotonic dystrophy type 1 (DM1) is a rare, inherited chronic progressive disease as well as an autosomal dominant multi-systemic disorder. It is probably one of the most common adult forms of muscular dystrophy, with a prevalence of approximately 10 per 100,000 people affected. With 733 million people in Europe, we estimate that 75,000 people in Europe are affected with DM1.

Methods/design: OPTIMISTIC is a multi-centre, randomised trial designed to compare an intervention comprising cognitive behavioural therapy (CBT) plus graded exercise therapy against standard care. Participants will be recruited from myotonic dystrophy clinics and neuromuscular centres in France, Germany, the Netherlands and the United Kingdom. A sample size of 208 individuals is needed. To allow for some potential loss to follow-up, a total of 296 male and female patients aged 18 years and older with genetically proven classical or adult DM1 and suffering from severe fatigue (only DM1 patients with a Checklist Individual Strength (CIS) subscale fatigue severity score ≥ 35 are likely to benefit from the intervention), able to walk independently and able to complete the trial interventions will be included. The primary outcome of the study is the score on the DM1-Activ scale, which is a measure of activity and participation for patients with DM1. Secondary outcomes include the 6-minute walk test, objective physical activity measured with an accelerometer, quality of life and cognitive measures. The trial will also collect data on potential effect modifiers of the short- and long-term clinical response, including pain, muscular impairment and cognitive-behavioural variables. In addition, OPTIMISTIC will identify genetic factors that predict outcome and potential biomarkers as surrogate outcome measures that best explain the observed clinical variation.

Discussion: OPTIMISTIC will not only provide effectiveness data on an intervention that could fill a treatment-gap for DM1 patients but will also improve our understanding of the relevant determinants of the prognosis of DM1.

Registration number: Cinicaltrials.gov NCT02118779; registered 11 April 2014.

Figures

Fig. 1
Fig. 1
Determinants of health status in DM1. Exercise therapy is intended to improve physical activity whereas cognitive behavioural therapy is intended to stimulate an active life-style by addressing perpetuating factors of fatigue such as lack of physical activity, motivation, pain and sleep disturbances and also by teaching patients to compensate for a lack of initiative (motivation)
Fig. 2
Fig. 2
OPTIMISTIC patient pathway. Visit 1 and visit 2 can be combined if appropriate and acceptable to participant. Duplicate tests and questionnaires will not be performed
Fig. 3
Fig. 3
OPTIMISTIC Study flowchart

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