Trial Review

Did you know?

The ANZCTR now automatically displays published trial results and simplifies the addition of trial documents such as unpublished protocols and statistical analysis plans.

These enhancements will offer a more comprehensive view of trials, regardless of whether their results are positive, negative, or inconclusive.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00468832




Registration number
NCT00468832
Ethics application status
Date submitted
1/05/2007
Date registered
3/05/2007
Date last updated
21/04/2016

Titles & IDs
Public title
Longitudinal Study of the Natural History of Duchenne Muscular Dystrophy (DMD)
Scientific title
Longitudinal Study of the Relationship Between Impairment, Activity Limitation, Participation and Quality of Life in Persons With Confirmed Duchenne Muscular Dystrophy (DMD)
Secondary ID [1] 0 0
UCD0305
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Duchenne Muscular Dystrophy 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
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.
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Strength and function
Timepoint [1] 0 0
Collected at yearly visits
Primary outcome [2] 0 0
Quality of life
Timepoint [2] 0 0
Collected at yearly visits
Primary outcome [3] 0 0
Medical history assessment
Timepoint [3] 0 0
Collected at yearly visits
Secondary outcome [1] 0 0
Biomarkers and genetic modifiers
Timepoint [1] 0 0
Collected either once at any visit or each visit

Eligibility
Key inclusion criteria
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
Minimum age
2 Years
Maximum age
30 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
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

Study design
Purpose
Duration
Selection
Timing
Prospective
Statistical methods / analysis

Recruitment
Recruitment status
UNKNOWN
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2005
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2019
Actual
Sample size
Target
Accrual to date
Final
551
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
The Children's Hospital at Westmead - Sydney
Recruitment hospital [2] 0 0
Royal Children's Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2145 - Sydney
Recruitment postcode(s) [2] 0 0
3052 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Minnesota
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Tennessee
Country [10] 0 0
United States of America
State/province [10] 0 0
Virginia
Country [11] 0 0
Argentina
State/province [11] 0 0
Buenos Aires
Country [12] 0 0
Canada
State/province [12] 0 0
Alberta
Country [13] 0 0
Canada
State/province [13] 0 0
Ontario
Country [14] 0 0
India
State/province [14] 0 0
Chennai
Country [15] 0 0
Israel
State/province [15] 0 0
Petach Tikvah
Country [16] 0 0
Italy
State/province [16] 0 0
Milan
Country [17] 0 0
Sweden
State/province [17] 0 0
Gothenburg

Funding & Sponsors
Primary sponsor type
Other
Name
Cooperative International Neuromuscular Research Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
U.S. Department of Education
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Government body
Name [2] 0 0
National Institutes of Health (NIH)
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Government body
Name [3] 0 0
United States Department of Defense
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Parent Project Muscular Dystrophy
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00468832
Trial related presentations / publications
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Craig McDonald, MD
Address 0 0
University of California, Davis
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00468832