Abstract
Objective To assess the ability of functional measures to detect disease progression in dysferlinopathy over 6 months and 1 year.
Methods One hundred ninety-three patients with dysferlinopathy were recruited to the Jain Foundation's International Clinical Outcome Study for Dysferlinopathy. Baseline, 6-month, and 1-year assessments included adapted North Star Ambulatory Assessment (a-NSAA), Motor Function Measure (MFM-20), timed function tests, 6-minute walk test (6MWT), Brooke scale, Jebsen test, manual muscle testing, and hand-held dynamometry. Patients also completed the ACTIVLIM questionnaire. Change in each measure over 6 months and 1 year was calculated and compared between disease severity (ambulant [mild, moderate, or severe based on a-NSAA score] or nonambulant [unable to complete a 10-meter walk]) and clinical diagnosis.
Results The functional a-NSAA test was the most sensitive to deterioration for ambulant patients overall. The a-NSAA score was the most sensitive test in the mild and moderate groups, while the 6MWT was most sensitive in the severe group. The 10-meter walk test was the only test showing significant change across all ambulant severity groups. In nonambulant patients, the MFM domain 3, wrist flexion strength, and pinch grip were most sensitive. Progression rates did not differ by clinical diagnosis. Power calculations determined that 46 moderately affected patients are required to determine clinical effectiveness for a hypothetical 1-year clinical trial based on the a-NSAA as a clinical endpoint.
Conclusion Certain functional outcome measures can detect changes over 6 months and 1 year in dysferlinopathy and potentially be useful in monitoring progression in clinical trials.
ClinicalTrials.gov identifier: NCT01676077.
Glossary
- a-NSAA=
- adapted North Star Ambulatory Assessment;
- COS=
- Jain Clinical Outcome Study in Dysferlinopathy;
- HHD=
- hand-held dynamometry;
- LGMD2B=
- limb girdle muscular dystrophy 2B;
- MFM=
- Motor Function Measure;
- MMT=
- manual muscle testing;
- 6MWT=
- 6-minute walk test;
- SRM=
- standardized response mean
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
The Jain COS Consortium coinvestigators are listed in the Appendix at the end of the article.
The Article Processing Charge was funded by the Jain Foundation.
- Received May 4, 2018.
- Accepted in final form October 1, 2018.
- Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
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