Clinical Outcome Evaluations and CBT Response Prediction in Myotonic Dystrophy

Abstract

Background: The European OPTIMISTIC clinical trial has demonstrated a significant, yet heterogenous effect of Cognitive Behavioural Therapy (CBT) for Myotonic Dystrophy type 1 (DM1) patients. One of its remaining aims was the assessment of efficacy and adequacy of clinical outcome measures, including the relatively novel primary trial outcome, the DM1-Activ-c questionnaire. Objectives: Assessment of the relationship between the Rasch-built DM1-Activ-c questionnaire and 26 commonly used clinical outcome measurements. Identification of variables associated with CBT response in DM1 patients. Methods: Retrospective analysis of the to date largest clinical trial in DM1 (OPTIMISTIC), comprising of 255 genetically confirmed DM1 patients randomized to either standard care or CBT with optionally graded exercise therapy. Correlations of 27 different outcome measures were calculated at baseline (cross-sectional) and of their respective intervention induced changes (longitudinal). Bootstrap enhanced Elastic-Net (BeEN) regression was validated and implemented to select variables associated with CBT response. Results: In cross-sectional data, DM1-Activ-c correlated significantly with the majority of other outcome measures, including Six Minute Walk Test and Myotonic Dystrophy Health Index. Fewer and weaker significant longitudinal correlations were observed. Nine variables potentially associated with CBT response were identified, including measures of disease severity, executive cognitive functioning and perceived social support. Conclusions: The DM1-Activ-c questionnaire appears to be a well suited cross-sectional instrument to assess a variety of clinically relevant dimensions in DM1. Yet, apathy and experienced social support measures were less well captured. CBT response was heterogenous, requiring careful selection of outcome measures for different disease aspects.

Clinical improvement of DM1 patients reflected by reversal of disease-induced gene expression in blood

“…In line with the results of an earlier study, we have illustrated that the clinical response towards the CBT intervention was rather heterogenous [21]. A novel addition to this finding was the illustration that this heterogeneity extends towards changes in molecular profiles within a 10-month timeframe.…”

“…Notably, the CBT intervention was tailored towards the specific needs of the patient in a shared decision-making process between the patient and the psychotherapist, allowing for a personalized intervention. The trial has shown significant, yet heterogenous improvements for various signs and symptoms, as well as the capacity for social activity and participation in DM1 [21].…”

Clinical improvement of DM1 patients reflected by reversal of disease-induced gene expression in blood

“…Notably, the CBT intervention was tailored towards the specific needs of the patient in a shared decision making process between patient and psychotherapist, allowing for a personalized intervention. The trial has shown significant, yet heterogenous improvements for various signs and symptoms, as well as the capacity for social activity and participation in DM1 [21].…”