TY - JOUR
T1 - Results of a two-year pilot study of clinical outcome measures in collagen VI- and laminin alpha2-related congenital muscular dystrophies
AU - Meilleur, Katherine G.
AU - Jain, Minal S.
AU - Hynan, Linda S.
AU - Shieh, Ching Yi
AU - Kim, Eunice
AU - Waite, Melissa
AU - McGuire, Michelle
AU - Fiorini, Courtney
AU - Glanzman, Allan M.
AU - Main, Marion
AU - Rose, Kristy
AU - Duong, Tina
AU - Bendixen, Roxanna
AU - Linton, Melody M.
AU - Arveson, Irene C.
AU - Nichols, Carmel
AU - Yang, Kelly
AU - Fischbeck, Kenneth H.
AU - Wagner, Kathryn R.
AU - North, Kathryn
AU - Mankodi, Ami
AU - Grunseich, Christopher
AU - Hartnett, Elizabeth J.
AU - Smith, Michaele
AU - Donkervoort, Sandra
AU - Schindler, Alice
AU - Kokkinis, Angela
AU - Leach, Meganne
AU - Foley, A. Reghan
AU - Collins, James
AU - Muntoni, Francesco
AU - Rutkowski, Anne
AU - Bönnemann, Carsten G.
N1 - Funding Information:
We would like to thank the following people without which this study would not have been possible: the participants and their families for their time, flexibility, and commitment during the two years of this study; the nurses and staff of the NIH Clinical Center's outpatient neurology clinic (year 1) and pediatric outpatient clinic (year 2); the National Heart Lung and Blood Institute's Pulmonary Function Lab physicians, therapists, and staff; Mrs. Livija Medne for her assistance with the study in year 2; Dr. Carole Vuillerot and Dr. Joan Austin for their critical feedback on the manuscript. This work was supported by Cure CMD and the NIH intramural funds of the NINDS, NINR, and Mark O. Hatfield Clinical Research Center.
Publisher Copyright:
© 2014.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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.
AB - 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.
KW - Clinical outcome measures
KW - Collagen VI related muscular dystrophy
KW - Laminin alpha 2 related dystrophy
KW - Motor function scales
KW - Neuromuscular disease
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UR - http://www.scopus.com/inward/citedby.url?scp=84919870981&partnerID=8YFLogxK
U2 - 10.1016/j.nmd.2014.09.010
DO - 10.1016/j.nmd.2014.09.010
M3 - Article
C2 - 25307854
AN - SCOPUS:84919870981
SN - 0960-8966
VL - 25
SP - 43
EP - 54
JO - Neuromuscular Disorders
JF - Neuromuscular Disorders
IS - 1
ER -