title: Results of a two-year pilot study of clinical outcome measures in collagen VI- and laminin alpha2-related congenital muscular dystrophies.
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 PedsQL(TM) 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 PedsQL(TM) 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.
authors.affiliation: National Institute of Nursing Research, NIH, Bethesda, MD, USA. Electronic address: meilleurk@mail.nih.gov.
authors.forename: Katherine G
authors.initials: KG
authors.lastname: Meilleur
authors.affiliation: Mark O. Hatfield Clinical Research Center, NIH, Bethesda, MD, USA.
authors.forename: Minal S
authors.initials: MS
authors.lastname: Jain
authors.affiliation: Departments of Clinical Sciences (Biostatistics) and Psychiatry, University of Texas Southwestern, Dallas, TX, USA.
authors.forename: Linda S
authors.initials: LS
authors.lastname: Hynan
authors.affiliation: National Institutes of Health, Bethesda, MD, USA.
authors.forename: Ching-Yi
authors.initials: CY
authors.lastname: Shieh
authors.affiliation: CureCMD, Los Angeles, CA, USA.
authors.forename: Eunice
authors.initials: E
authors.lastname: Kim
authors.affiliation: Mark O. Hatfield Clinical Research Center, NIH, Bethesda, MD, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Waite
authors.affiliation: Pediatric Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: McGuire
authors.affiliation: The Kennedy Krieger Institute and the Departments of Neurology and Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Courtney
authors.initials: C
authors.lastname: Fiorini
authors.affiliation: Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Allan M
authors.initials: AM
authors.lastname: Glanzman
authors.affiliation: Dubowitz Neuromuscular Centre, MRC Centre for Neuromuscular Diseases, University College London Institute of Child Health and Great Ormond Street Hospital for Children, London, UK.
authors.forename: Marion
authors.initials: M
authors.lastname: Main
authors.affiliation: Institute for Neuroscience and Muscle Research at The Children's Hospital at Westmead, Sydney, Australia.
authors.forename: Kristy
authors.initials: K
authors.lastname: Rose
authors.affiliation: Children's National Medical Center, Washington, DC, USA.
authors.forename: Tina
authors.initials: T
authors.lastname: Duong
authors.affiliation: University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Roxanna
authors.initials: R
authors.lastname: Bendixen
authors.affiliation: National Institute of Nursing Research, NIH, Bethesda, MD, USA.
authors.forename: Melody M
authors.initials: MM
authors.lastname: Linton
authors.affiliation: National Institute of Nursing Research, NIH, Bethesda, MD, USA.
authors.forename: Irene C
authors.initials: IC
authors.lastname: Arveson
authors.affiliation: Mark O. Hatfield Clinical Research Center, NIH, Bethesda, MD, USA.
authors.forename: Carmel
authors.initials: C
authors.lastname: Nichols
authors.affiliation: National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Yang
authors.affiliation: National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA.
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Fischbeck
authors.affiliation: The Kennedy Krieger Institute and the Departments of Neurology and Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: Wagner
authors.affiliation: Institute for Neuroscience and Muscle Research at The Children's Hospital at Westmead, Sydney, Australia.
authors.forename: Kathryn
authors.initials: K
authors.lastname: North
authors.affiliation: National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA.
authors.forename: Ami
authors.initials: A
authors.lastname: Mankodi
authors.affiliation: National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Grunseich
authors.affiliation: National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Hartnett
authors.affiliation: Mark O. Hatfield Clinical Research Center, NIH, Bethesda, MD, USA.
authors.forename: Michaele
authors.initials: M
authors.lastname: Smith
authors.affiliation: National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Donkervoort
authors.affiliation: National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA.
authors.forename: Alice
authors.initials: A
authors.lastname: Schindler
authors.affiliation: National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Kokkinis
authors.affiliation: Children's National Medical Center, Washington, DC, USA; National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA.
authors.forename: Meganne
authors.initials: M
authors.lastname: Leach
authors.affiliation: Dubowitz Neuromuscular Centre, MRC Centre for Neuromuscular Diseases, University College London Institute of Child Health and Great Ormond Street Hospital for Children, London, UK.
authors.forename: A Reghan
authors.initials: AR
authors.lastname: Foley
authors.affiliation: Pediatric Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: James
authors.initials: J
authors.lastname: Collins
authors.affiliation: Dubowitz Neuromuscular Centre, MRC Centre for Neuromuscular Diseases, University College London Institute of Child Health and Great Ormond Street Hospital for Children, London, UK.
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
authors.affiliation: CureCMD, Los Angeles, CA, USA; Kaiser SCPMG, Los Angeles, CA, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Rutkowski
authors.affiliation: National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA. Electronic address: carsten.bonnemann@nih.gov.
authors.forename: Carsten G
authors.initials: CG
authors.lastname: Bönnemann
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D024142:Collagen Type VI / Q000235:genetics*; D005080:Exercise Test; D005260:Female; D006801:Humans; D007797:Laminin / Q000235:genetics*; D008297:Male; D009136:Muscular Dystrophies / Q000151:congenital / Q000628:therapy*; D009154:Mutation; D010865:Pilot Projects; D011788:Quality of Life; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D024142:Collagen Type VI; D007797:Laminin; C102645:laminin alpha 2
keywords: Clinical outcome measures; Collagen VI related muscular dystrophy; Laminin alpha 2 related dystrophy; Motor function scales; Neuromuscular disease