Longitudinal Study of the Natural History of Duchenne Muscular Dystrophy (DMD)
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|ClinicalTrials.gov Identifier: NCT00468832|
Recruitment Status : Unknown
Verified April 2016 by Cooperative International Neuromuscular Research Group.
Recruitment status was: Active, not recruiting
First Posted : May 3, 2007
Last Update Posted : April 21, 2016
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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.
|Condition or disease|
|Duchenne Muscular Dystrophy|
|Study Type :||Observational|
|Actual Enrollment :||551 participants|
|Official Title:||Longitudinal Study of the Relationship Between Impairment, Activity Limitation, Participation and Quality of Life in Persons With Confirmed Duchenne Muscular Dystrophy (DMD)|
|Study Start Date :||December 2005|
|Estimated Primary Completion Date :||December 2019|
|Estimated Study Completion Date :||December 2019|
Ongoing Duchenne Muscular Dystrophy (DMD) Cohort
340 patients currently enrolled participants with DMD.
New Young Duchenne Muscular Dystrophy (DMD) Cohort
Additional 100 confirmed DMD participants aged 4-7 years old to be recruited.
Typically Developing Control Cohort
Up to 370 typically developing male children and adults aged 6-30 years old to be recruited.
- Strength and function [ Time Frame: 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 [ Time Frame: 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
- Medical history assessment [ Time Frame: Collected at yearly visits ]Outcomes on ambulation status, medication history, hospitalizations, surgeries, nutrition, fractures, and cardiac tests.
- Biomarkers and genetic modifiers [ Time Frame: 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)
Biospecimen Retention: Samples With DNA
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|Ages Eligible for Study:||2 Years to 30 Years (Child, Adult)|
|Sexes Eligible for Study:||Male|
|Accepts Healthy Volunteers:||Yes|
|Sampling Method:||Non-Probability Sample|
The incidence of DMD is considered equal across racial and ethnic groups. At the start of the CINRG program, it was assumed by investigators that the aggregate subject populations of the participating US sites should closely mirror the racial and ethnic distribution of the US population.
DMD is an X-linked recessive disease affecting only males. However, female carriers of the disease can be symptomatic due to skewed X-inactivation, a secondary genetic event. We have opted to study the most commonly affected population, males, to ensure subject homogeneity. As such, there are no outreach programs planned for women in this study.
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.
NOTE: Determination of the appropriate clinical symptoms consistent with DMD will generally be the responsibility of the clinician. At a minimum this will include progressive loss of function, with additional consideration for other clinical features such as a characteristic gait, a positive Gower sign and calf pseudohypertrophy. When immunostaining of muscle biopsy is used to determining case definition, the clinical reviewer (site PI) should confirm that appropriate testing has ruled out a secondary deficiency of dystrophin. Affected subjects that do not exhibit the above symptoms consistent with DMD should be excluded.
o 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
Controls 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00468832
|Study Chair:||Craig McDonald, MD||University of California, Davis|
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
|Responsible Party:||Cooperative International Neuromuscular Research Group|
|Other Study ID Numbers:||
|First Posted:||May 3, 2007 Key Record Dates|
|Last Update Posted:||April 21, 2016|
|Last Verified:||April 2016|
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked