Abstract
Objective To assess the association between variant repeat (VR) interruptions in patients with myotonic dystrophy type 1 (DM1) and clinical symptoms and outcome measures after cognitive behavioral therapy (CBT) intervention.
Methods Adult patients with DM1 were recruited within the OPTIMISTIC trial (NCT02118779). Disease-related history, current clinical symptoms and comorbidities, functional assessments, and disease- and health-related questionnaires were obtained at baseline and after 5 and 10 months. After genetic analysis, we assessed the association between the presence of VR interruptions and clinical symptoms' long-term outcomes and compared the effects of CBT in patients with and without VR interruptions. Core trial outcome measures analyzed were: 6-minute walking test, DM1-Activ-C, Checklist Individual Strength Fatigue Score, Myotonic Dystrophy Health Index, McGill-Pain questionnaire, and Beck Depression inventory—fast screen. Blood samples for DNA testing were obtained at the baseline visit for determining CTG length and detection of VR interruptions.
Results VR interruptions were detectable in 21/250 patients (8.4%)—12 were assigned to the standard-of-care group (control group) and 9 to the CBT group. Patients with VR interruptions were significantly older when the first medical problem occurred and had a significantly shorter disease duration at baseline. We found a tendency toward a milder disease severity in patients with VR interruptions, especially in ventilation status, mobility, and cardiac symptoms. Changes in clinical outcome measures after CBT were not associated with the presence of VR interruptions.
Conclusions The presence of VR interruptions is associated with a later onset of the disease and a milder phenotype. However, based on the OPTIMISTIC trial data, the presence of VR interruptions was not associated with significant changes on outcome measures after CBT intervention.
Trial Registration Information ClinicalTrials.gov NCT02118779.
Glossary
- 6MWT=
- 6-minute walking test;
- BDI-Fs=
- Beck Depression inventory—fast screen;
- CBT=
- cognitive behavioral therapy;
- CIS=
- Checklist Individual Strength;
- DM1=
- myotonic dystrophy type 1;
- ePAL=
- estimating the progenitor allele length;
- MDHI=
- Myotonic Dystrophy Health Index;
- PROM=
- patient-reported outcome measure;
- SAP=
- statistical analysis plan;
- VR=
- variant repeat
Footnotes
Go to Neurology.org/NG for full disclosures. Funding information is provided at the end of the article.
OPTIMISTIC Consortium coinvestigators are listed at appendix 2 at the end of the article.
The Article Processing Charge was funded by the authors.
- Received September 23, 2020.
- Accepted in final form February 4, 2021.
- Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
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