Published on Tue, 07/17/2018

The Premise and the Plan

OPTIMISTIC (Observational Prolonged Trial In Myotonic dystrophy type 1 to Improve Quality of Life—Standards, a Target Identification Collaboration) [Link to archived site], an international, multi-center randomized clinical study funded by the European Commission and coordinated by Dr. Baziel van Engelen (Nijmegen, Netherlands), has achieved the milestone of publication of results in Lancet Neurology. A major driving factor for the study was the relative lack and small size of prior clinical trials in DM1. Thus, in addition to directly testing the value of exercise therapy and cognitive behavioral therapy against standard of care, the premise of OPTIMISTIC included gaining insights into outcome measures, use of genetic analysis and cardiac screening, and putative biomarkers to improve clinical trial readiness for DM1.

The specific goals of the OPTIMISTIC trial were to evaluate and compare: (a) exercise therapy to maintain or improve patient functional capacity and (b) cognitive behavioral therapy to simulate an active lifestyle and improve skeletal muscle function. Collectively, the interventions were tested as to their ability to improve DM1 patient quality of life. The intent of the OPTIMISTIC consortium is that study data may prove useful in providing clinical management guidance to both practitioners and patients to reduce the devastating symptom of fatigue and thereby improve quality of life.

The Trial and Outcomes

A total of 255 adult subjects with genetically confirmed DM1 and severe fatigue were recruited into OPTIMISTIC at four neuromuscular centers and randomly assigned to cognitive behavioral therapy plus standard of care or standard of care alone; a subset of the cognitive behavioral therapy plus standard of care group also received a graded exercise module. The primary outcome measure was 10-month change from baseline in the DM1-Activ-c scale.

The cognitive behavioral therapy group showed an adjusted mean difference improvement of 1.53 points in DM1-Activ-c versus an adjusted mean difference decline of 2.02 in the standard of care alone group. Differences in favor of the cognitive behavioral therapy intervention were noted for several secondary outcome measures as well (e.g., 6MWT, fatigue and daytime sleepiness scale, CIS-fatigue). Prior studies suggested that low to moderate intensity exercise was beneficial in DM1. While addition of graded exercise in a subset of the cognitive behavioral therapy group helped address fatigue and increased physical activity and participation (as evidenced by DM1-Activ-c), there was no improvement in self-reported quality of life. Adverse events and serious adverse events were approximately equal across these treatment groups—although study data indicated that efforts should be included to prevent falls when implementing the cognitive behavioral therapy paradigm into rehabilitation programs.

Taken together, the research team concluded that cognitive behavioral therapy alone resulted in improved capacity for activity and social participation in severely fatigued adult patients over the 10-month study period and stated that the approach could be considered in this group of DM1 patients. The knowledge and experience gained in the OPTIMISTIC trial experience should carry forward in the design, conduct, and analysis of future interventional clinical trials in DM1.


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 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; OPTIMISTIC consortium.
Lancet Neurol. 2018 Jun 18. pii: S1474-4422(18)30203-5. doi: 10.1016/S1474-4422(18)30203-5. [Epub ahead of print]


OPTIMISTIC ClinicalTrials.gov Entry
Observational Prolonged Trial in Myotonic Dystrophy Type 1 (OPTIMISTIC)