Longitudinal Study of the Natural History of Duchenne Muscular Dystrophy (DMD)

NCT00468832 | Unknown DMC

• 1 other identifier: UCD0305
• Study Type: observational
• Target: 551
• Locations: 8 countries
• Sites: 21

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.

Conditions

Duchenne Muscular Dystrophy

Outcome Measures

Primary Outcomes (3)

• Strength and function

  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).

  Collected at yearly visits

• Quality of life

  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

  Collected at yearly visits

• Medical history assessment

  Outcomes on ambulation status, medication history, hospitalizations, surgeries, nutrition, fractures, and cardiac tests.

  Collected at yearly visits

Secondary Outcomes (1)

• Biomarkers and genetic modifiers

  Collected either once at any visit or each visit

Study Arms (3)

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.

Eligibility Criteria

• Age: 2 Years - 30 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• 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.
• 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)

You may not qualify if:

• 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
• Male sex
• Age 6-30 years
• Able to comply with functional testing instructions
• 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
• 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

Sponsors & Collaborators

• Cooperative International Neuromuscular Research Group: lead
• U.S. Department of Education: collaborator
• National Institutes of Health (NIH): collaborator
• United States Department of Defense: collaborator
• Parent Project Muscular Dystrophy: collaborator

Study Sites (21)

University of California, Davis

Sacramento, California, 95817, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

University of of Florida

Gainesville, Florida, 32610, United States

Location

Lurie Children's Hospial

Chicago, Illinois, 60614, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Washington University, St. Louis

St Louis, Missouri, 63110, United States

Location

Carolinas Medical Center

Charlotte, North Carolina, 28207, United States

Location

Duke Children's Hospital

Durham, North Carolina, 27710, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Tennessee

Memphis, Tennessee, 38104, United States

Location

Children's Hospital of Virginia

Richmond, Virginia, 23220, United States

Location

Fundacion Favaloro

Buenos Aires, 1434, Argentina

Location

The Children's Hospital at Westmead

Sydney, New South Wales, 2145, Australia

Location

Royal Children's Hospital

Melbourne, Victoria, 3052, Australia

Location

Alberta Children's Hospital

Calgary, Alberta, T2T 5C7, Canada

Location

University of Alberta

Edmonton, Alberta, T6G 2J3, Canada

Location

Holland Bloorview Kids Rehab Hospital

Toronto, Ontario, M4G 1R8, Canada

Location

Apollo Hospitals

Chennai, India

Location

Schneider Children's Medical Center of Israel

Petach Tikvah, Israel

Location

NEMO

Milan, Italy

Location

Queen Silvia Children's Hospital

Gothenburg, Sweden

Location

Related Publications (2)

• Thangarajh M, Spurney CF, Gordish-Dressman H, Clemens PR, Hoffman EP, McDonald CM, Henricson EK; CINRG Investigators. Neurodevelopmental Needs in Young Boys with Duchenne Muscular Dystrophy (DMD): Observations from the Cooperative International Neuromuscular Research Group (CINRG) DMD Natural History Study (DNHS). PLoS Curr. 2018 Oct 17;10:ecurrents.md.4cdeb6970e54034db2bc3dfa54b4d987. doi: 10.1371/currents.md.4cdeb6970e54034db2bc3dfa54b4d987.

  PMID: 30443431 DERIVED

• McDonald CM, Henricson EK, Abresch RT, Duong T, Joyce NC, Hu F, Clemens PR, Hoffman EP, Cnaan A, Gordish-Dressman H; CINRG Investigators. Long-term effects of glucocorticoids on function, quality of life, and survival in patients with Duchenne muscular dystrophy: a prospective cohort study. Lancet. 2018 Feb 3;391(10119):451-461. doi: 10.1016/S0140-6736(17)32160-8. Epub 2017 Nov 22.

  PMID: 29174484 DERIVED

Related Links

• CINRG Website

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples are being collected for single-nucleotide polymorphism, Genome-wide Association Study, and biomarker analyses.

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Craig McDonald, MD

  University of California, Davis

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2007
• First Posted: May 3, 2007
• Study Start: December 1, 2005
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: April 21, 2016

Record last verified: 2016-04

Locations

IT (1); AU (2); CA (3); IN (1); US (11); SE (1); IL (1); AR (1)