Longitudinal Study of the Natural History of Duchenne Muscular Dystrophy (DMD)
- Conditions
- Duchenne Muscular Dystrophy
- Registration Number
- NCT00468832
- Lead Sponsor
- Cooperative International Neuromuscular Research Group
- Brief Summary
The purpose of this study is to establish the largest long-term assessment of people with Duchenne muscular dystrophy (DMD). In this study, the investigators associated with the Cooperative International Neuromuscular Research Group CINRG) will take a detailed look (for a minimum of eight years) at DMD participant's physical abilities, the medical problems they experience, and how they use health care services. Physical abilities will be compared to a group of healthy controls.
The second purpose of this study is to find out whether small, normal differences in the genetic makeup of people with DMD (called "single nucleotide polymorphisms" or "SNPs") affect how their disease progresses and relates to muscle strength/size and steroid response.
The third purpose of this study is to study genetic variations associated with DMD.
The final purpose of this study is to determine whether certain biomarkers are present in people with DMD and not in healthy controls.
- Detailed Description
Phenotyping Study Aims
Aim 1: Longitudinally assess body function and body structure (impairment) through the measurement of anthropometrics, muscle strength and pulmonary function in subjects with DMD through the multicenter CINRG network.
Aim 2: Longitudinally assess activity limitations in subjects with DMD through CINRG with timed motor performance, burden of care, and functional status.
Aim 3: Longitudinally assess secondary conditions in subjects with DMD, and relative risks of developing those conditions based on exposure to preventive interventions.
Aim 4: Longitudinally assess participation, life satisfaction, service utilization and health-related quality of life in subjects with DMD.
Aim 5: Determine appropriate outcome measurements for impairment, activities (activity limitations), participation and quality of life to determine the effect of prednisone and other therapeutic interventions on these factors.
Aim 6: Using the most robust impairment, activity, participation and quality of life outcome measures, determine the sample size, power and statistical methods for the analysis of the effect size for future planned randomized-controlled rehabilitation interventions in DMD.
Aim 7: Examine the associations between interventions and incidence and severity of secondary conditions, achievement of disease milestones and measures of motor function and mobility.
Aim 8: To assess the validity and responsiveness of novel clinical outcome measures in DMD, including the 6-minute walk test (6MWT), the 9-hole peg test (9-HPT) Egen Klassification Scale(EK), the North Star Ambulatory Assessment (NSAA), and quantitative key and pinch grip strength testing.
Aim 9: To assess the reliability, validity and responsiveness of novel patient-reported outcome(PRO) measures in DMD, including the NeuroQOL and PedsQL Neuromuscular Module.
Aim 10: To assess the clinical meaningfulness of novel objective clinical outcome measures by assessing their ability to predict milestones of loss of ability to stand from supine, to stand from a seated position, to climb stairs, to ambulate independently and to raise a hand to the mouth.
AIM 11: To determine the impact of development and growth on outcome measure performance,we will assess physical function on a group of healthy, typically developing male children and adults between 6 and 30 years of age for outcome measures of motor function and strength including the9-HPT, 6MWT, NSAA, timed function tests and quantitative muscle strength (QMT). Test results from this cohort will be used to develop initial percent predicted for age values for these assessments.
SNP Genotyping Study Aim
Our goal of the proposed study is to define polygenic modifiers of disease progression, and also response to treatment with glucocorticoids (prednisone and deflazacort). The most common type of human genetic variation is the single-nucleotide polymorphism (SNP, a base position at which two alternative bases occur at an appreciable frequency (\>1%) in the population. SNPs are 90% of variation in the human genome. SNPs occur on the average of 1 per 1000 to 2000 bp throughout the 3.2 billion bp of the human genome while coding region SNPs (cSNPs) occur on the average of 1 per 346 bp.
Genome-wide Association Study Aim
Our goal of the proposed study is to isolate genomic DNA and find possible correlations of clinical phenotypes with gene loci associated with mild vs. severe clinical presentation, progression, or response to steroids.
Serum Biomarkers Study Aim
Our goal is to discover and validate sensitive and specific serum biomarkers for DMD.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- Male
- Target Recruitment
- 551
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Medical history assessment Collected at yearly visits Outcomes on ambulation status, medication history, hospitalizations, surgeries, nutrition, fractures, and cardiac tests.
Strength and function Collected at yearly visits These assessments include:
* Quantitative muscle testing
* Manual muscle testing
* Pulmonary function testing
* Functional evaluations (nine hole peg, six minute walk, North Star ambulatory assessment, Brooke and Vignos scales, Egen Klassification (EK) scale, and range of motion).Quality of life Collected at yearly visits These questionnaires include:
* Pediatric Quality of Life Inventory (PedsQL)
* Pediatric Orthopaedic Functional Health Questionnaire of the Pediatric Orthopaedic Society of North America (POSNA)
* World Health Organization Quality of Life Assessment - Brief (WHO QOL Brief)
* Pediatrics and Adult Neuromuscular module Quality of Life (NeuroQOL)
* Review of Systems
- Secondary Outcome Measures
Name Time Method Biomarkers and genetic modifiers Collected either once at any visit or each visit Genotyping and Serum Biomarkers include blood/saliva collection for:
* Blood collection for Genome Wide Association Study (GWAS) analysis (one time sample, any visit)
* Blood or saliva collection for SNP sample (one time sample, any visit)
* Blood collection for biomarker analysis (collected at each visit)
Trial Locations
- Locations (21)
University of California, Davis
🇺🇸Sacramento, California, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
University of of Florida
🇺🇸Gainesville, Florida, United States
Lurie Children's Hospial
🇺🇸Chicago, Illinois, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Washington University, St. Louis
🇺🇸St. Louis, Missouri, United States
Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
Duke Children's Hospital
🇺🇸Durham, North Carolina, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
University of Tennessee
🇺🇸Memphis, Tennessee, United States
Scroll for more (11 remaining)University of California, Davis🇺🇸Sacramento, California, United States