Results of a two-year pilot study of clinical outcome measures in collagen VI- and laminin alpha2-related congenital muscular dystrophies

Katherine G. Meilleur, Minal S. Jain, Linda S. Hynan, Ching Yi Shieh, Eunice Kim, Melissa Waite, Michelle McGuire, Courtney Fiorini, Allan M. Glanzman, Marion Main, Kristy Rose, Tina Duong, Roxanna Bendixen, Melody M. Linton, Irene C. Arveson, Carmel Nichols, Kelly Yang, Kenneth H. Fischbeck, Kathryn R. Wagner, Kathryn NorthAmi Mankodi, Christopher Grunseich, Elizabeth J. Hartnett, Michaele Smith, Sandra Donkervoort, Alice Schindler, Angela Kokkinis, Meganne Leach, A. Reghan Foley, James Collins, Francesco Muntoni, Anne Rutkowski, Carsten G. Bönnemann

Research output: Contribution to journalArticle

Abstract

Potential therapies are currently under development for two congenital muscular dystrophy (CMD) subtypes: collagen VI-related muscular dystrophy (COL6-RD) and laminin alpha 2-related dystrophy (LAMA2-RD). However, appropriate clinical outcome measures to be used in clinical trials have not been validated in CMDs. We conducted a two-year pilot study to evaluate feasibility, reliability, and validity of various outcome measures, particularly the Motor Function Measure 32, in 33 subjects with COL6-RD and LAMA2-RD. In the first year, outcome measures tested included: Motor Function Measure 32 (MFM32), forced vital capacity (FVC) percent predicted sitting, myometry, goniometry, 10-meter walk, Egen Klassification 2, and PedsQLTM Generic and Neuromuscular Cores. In the second year, we added the North Star Ambulatory Assessment (NSAA), Hammersmith Functional Motor Scale (HFMS), timed functional tests, Measure of Activity Limitations (ACTIVLIM), Quality of Upper Extremity Skills Test (QUEST), and Patient-Reported Outcomes Measurement Information System (PROMIS) fatigue subscale. The MFM32 showed strong inter-rater (0.92) and internal consistency (0.96) reliabilities. Concurrent validity for the MFM32 was supported by large correlations (range 0.623-0.936) with the following: FVC, NSAA, HFMS, timed functional tests, ACTIVLIM, and QUEST. Significant correlations of the MFM32 were also found with select myometry measurements, mainly of the proximal extremities and domains of the PedsQLTM scales focusing on physical health and neuromuscular disease. Goniometry measurements were less reliable. The Motor Function Measure is reliable and valid in the two specific subtypes of CMD evaluated, COL6-RD and LAMA2-RD. The NSAA is useful as a complementary outcome measure in ambulatory individuals. Preliminary concurrent validity of several other clinical outcome measures was also demonstrated for these subtypes.

Original languageEnglish (US)
Pages (from-to)43-54
Number of pages12
JournalNeuromuscular Disorders
Volume25
Issue number1
DOIs
StatePublished - Jan 1 2015

    Fingerprint

Keywords

  • Clinical outcome measures
  • Collagen VI related muscular dystrophy
  • Laminin alpha 2 related dystrophy
  • Motor function scales
  • Neuromuscular disease

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Neurology
  • Clinical Neurology
  • Genetics(clinical)

Cite this

Meilleur, K. G., Jain, M. S., Hynan, L. S., Shieh, C. Y., Kim, E., Waite, M., McGuire, M., Fiorini, C., Glanzman, A. M., Main, M., Rose, K., Duong, T., Bendixen, R., Linton, M. M., Arveson, I. C., Nichols, C., Yang, K., Fischbeck, K. H., Wagner, K. R., ... Bönnemann, C. G. (2015). Results of a two-year pilot study of clinical outcome measures in collagen VI- and laminin alpha2-related congenital muscular dystrophies. Neuromuscular Disorders, 25(1), 43-54. https://doi.org/10.1016/j.nmd.2014.09.010