DMD Longitudinal Natural History Study
Natural History Studies – Neuromuscular Research Center
UCD0305: A longitudinal study of the relationship between impairment, activity limitation, participation and quality of life in persons with confirmed Duchenne muscular dystrophy (DMD).
The purpose of this study is to continue a world-wide, long-term study of people with Duchenne muscular dystrophy (DMD) that is now following 340 families at universities and clinics around the world. Through this study we are evaluating different measures of strength and function that researchers can use in tests of new therapies. For this part of our study, we are seeking two new cohorts, 1) a new group of children diagnosed with DMD aged 4-8, and 2) a group of typically-developing male participants’ ages 6 to 30 years old without Duchenne muscular dystrophy (“healthy male controls”). Another purpose of this study is to collect a sample of blood to evaluate potential biomarkers that are associated with disease progression and response to steroid therapy.
There are no interventions for this study. We call these studies "Natural History Studies."
DMD Subject Inclusion Criteria:
- Affected subjects must be male and between the ages of 2 and 30
Affected subjects between the ages of 2 and 4 must have a diagnosis of DMD confirmed by at least one the following OR have an older male sibling that meet at least one of the following criteria:
- Dystrophin immunofluorescence and/or immunoblot showing complete dystrophin deficiency, and clinical picture consistent with typical Duchenne dystrophy OR
- Gene deletion test positive (missing one or more exons) in the central rod domain exons 25-60) of dystrophin, where reading frame can be predicted as 'out-of-frame',and clinical picture consistent with typical Duchenne dystrophy.
- Complete dystrophin gene sequencing showing an alteration (point mutation, duplication, other) that is expected to preclude production of the dystrophin protein(i.e. nonsense mutation, deletion/duplication leading to a downstream stop codon),with a typical clinical picture of DMD.
Affected subjects between the ages of 5 and 30 must either fulfill the above criteria OR show evidence of a dystrophinopathy and clinical picture consistent with Duchenne Muscular Dystrophy
- Participants who have documented clinical symptoms referable to a dystrophinopathy and direct support of the diagnosis by either (1) a positive DNA analysis for dystrophin mutation, (2) a muscle biopsy demonstrating abnormal dystrophin, or (3) an elevated CK (>5X normal), and X-linked pedigree and an affected family member who meets either criterion (1) or (2) as described above.
- Muscle weakness prevalent by 5 years of age
- Non-affected adult subjects must be Parent(s) or legal guardian(s) of an eligible affected subject.
DMD Serum Biomarker Inclusion Criteria:
- Participants must meet eligibility criteria for the DMD phenotyping portion of this study
- For the GC-treatment response cohort, participants must initiate GC treatment within the first year of study participation (i.e. between their first study visit and their one year follow-up visit)
DMD Subject Exclusion Criteria:
- For those subjects that confirm DMD diagnosis through a clinical picture consistent with DMD
- Steroid-naïve subjects ambulating past the 13th birthday
- Steroid users ambulating past the 16th birthday
- Subjects/families who are unwilling or unable to comply with the protocol study procedures or visits
Control Subject Inclusion Criteria:
- Male sex
- Age 6-30 years
- Able to comply with functional testing instructions
Control Serum Biomarker Inclusion Criteria:
- Participants must be male
- Participants must be free of DMD, other neuromuscular disease, or other significant concomitant illness
- Participant must be free of glucocorticoid therapy
Control Subject Exclusion Criteria:
- Musculoskeletal disease
- Musculoskeletal injury within 6 months of enrollment
- Other concomitant illness that precludes functional testing in the judgment of the investigator or clinical evaluator
- Completion of enrollment for age cohort