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Characterization of Clinical Skeletal and Cardiac Impairment in Carriers of DMD and BMD

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ClinicalTrials.gov Identifier: NCT02972580
Recruitment Status : Recruiting
First Posted : November 23, 2016
Last Update Posted : August 31, 2023
Sponsor:
Collaborator:
Parent Project Muscular Dystrophy
Information provided by (Responsible Party):
May Ling Mah, Nationwide Children's Hospital

Tracking Information
First Submitted Date July 25, 2016
First Posted Date November 23, 2016
Last Update Posted Date August 31, 2023
Study Start Date June 2016
Estimated Primary Completion Date December 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: May 22, 2018)
Compromise of cardiac function based on Cardiac Magnetic Resonance Imaging [ Time Frame: 2 years ]
Cardiac function as compromised by evidence of scarring of cardiac muscles, particularly of the base of the left ventricle via cardiac MRI studies with gadolinium contrast.
Original Primary Outcome Measures
 (submitted: November 21, 2016)
  • Cardiac Function [ Time Frame: 2 years ]
    Cardiac function as defined by cardiac MRI studies and treadmill SVO2
  • Skeletal Muscle Strength [ Time Frame: 2 years ]
Change History
Current Secondary Outcome Measures
 (submitted: November 5, 2018)
  • Cardiac Function Assessment Treadmill SVO2 [ Time Frame: 2 years ]
    Stress on heart muscle measured by SVO2 (percentage of oxygen saturation in the blood of the pulmonary artery). SVO2 represents an average of all the venous oxygen saturation of major organs and tissues. This measure provides assessment of cardiopulmonary function and helps measure the degree of cardiac instability and can be an indicator of deterioration from normal.
  • Physical Therapy Assessments Maximum Voluntary Isometric Contraction Testing [ Time Frame: 2 Years ]
    MVICT measures strength of skeletal muscles by assessing the force generated by by individual muscles. The results can be compared to norms and deterioration can be assessed over time.
  • Physical Therapy Assessments 6 Minute Walk Test [ Time Frame: 2 years ]
    A timed test to assess distance walked in 6 minutes is very quantitative and can be assessed in comparison to normal controls. Deterioration over time can be clearly measured.
  • Physical Therapy Assessments ACTIVE-seated [ Time Frame: 2 Years ]
    Exploratory outcome quantifying upper extremity reaching ability using a custom-designed game telling how far the arm reaches in comparison to overall functional ability of the individual ability.
  • Physical Therapy Assessments Time-to-Rise [ Time Frame: 2 Years ]
    A timed-test to measure ability to rise from the floor is quantifiable and measuring over time tells if there is loss of function.
  • Laboratory biomarkers - Creatine Kinase [ Time Frame: 2 Years ]
    CK levels are an indicator of muscle breakdown.
  • Laboratory biomarkers - C-Reactive Protein [ Time Frame: 2 Years ]
    Pro-inflammatory marker indicating the degree of inflammation of muscle when there is muscle breakdown.
  • Laboratory biomarkers - Interleukin-6 [ Time Frame: 2 Years ]
    Pro-inflammatory marker indicating the degree of inflammation of muscle when there is muscle breakdown.
  • Laboratory biomarkers - Cortisol levels [ Time Frame: 2 Years ]
    Hair cortisol levels measure stress levels as a means of understanding coping with disease.
  • Cognitive Assessment [ Time Frame: 2 Years ]
    Cognitive function measured by Wechsler Abbreviated Scale of Intelligence (WASI) provides a possible tool to measure disease awareness and establish if IQ level correlates with disease-related stress.
  • Caregiver Stress [ Time Frame: 2 Years ]
    Online self-report survey to assess stress burden on caregiver.
  • Pulmonary function testing (PFTs) [ Time Frame: 2 Years ]
    Stable or improved FVC
Original Secondary Outcome Measures
 (submitted: November 21, 2016)
  • Laboratory biomarkers [ Time Frame: 2 years ]
    Laboratory biomarkers of disease and stress burden: CK enzyme level, hair cortisol levels, pro-inflammatory markers
  • WAISI [ Time Frame: 2 years ]
    WAISI online survey for caregiver stress
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Characterization of Clinical Skeletal and Cardiac Impairment in Carriers of DMD and BMD
Official Title Characterization of Clinical Skeletal and Cardiac Impairment in Carriers of Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD)
Brief Summary Longitudinal prospective observational study. This is a 24-month study with the possibility of extending the data time points. Initially baseline, then 12 and 24 months follow up studies will be completed.
Detailed Description Four cohorts are enrolled in this study. The target population is the cohort of genetically confirmed DMD/BMD female carriers (Cohort A). This cohort will consist of 150 DMD/BMD mothers who are somatic carriers of a mutation in the DMD gene. The data collected for this cohort will be compared to three control groups; Control Group B is a cohort of 50 DMD/BMD mothers who are NOT somatic carriers, Control Group C is a cohort of 50 age-matched healthy controls and Control Group D is a cohort of 25 genetically confirmed carriers who do not have an affected child. The inclusion of a Control Group B allows for a comparison to a group of mothers that share the emotional and cognitive burden of caring for an affected male without having the physical or cognitive risks of being a female carrier. The Control Group C offers robust data from an age-matched healthy cohort for purposes of comparison. Control Group D allows for comparison to a group of women that have the same physical or cognitive risks as the Cohort A female carriers, but do not have the same burden of care giving.
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
The blood sample for genetic testing will be delivered to the Molecular Genetics lab at Nationwide Children's Hospital, where genomic DNA will be isolated from peripheral white blood cells. DNA will be banked frozen while a portion of the sample will be delivered to the Emory Molecular Genetics Laboratories for testing of the DMD gene.
Sampling Method Non-Probability Sample
Study Population Cohort A: DMD/BMD Female Carriers who have/had an affected child (n=150) Cohort B: DMD/BMD Female non-carriers controls who have/had an affected child (n=50) Cohort C: Healthy Age-Matched Controls (n=50) Cohort D: DMD/BMD Female Carriers who do not have/had an affected child (n=25)
Condition
  • Duchenne Muscular Dystrophy
  • Becker Muscular Dystrophy
Intervention Genetic: Genetic characterization
Confirmatory genetic testing for mutation in DMD gene (Carrier Status) for subjects in respective Cohorts
Study Groups/Cohorts
  • Cohort A
    DMD/BMD Female Carriers who have/had an affected child (n=150)
    Intervention: Genetic: Genetic characterization
  • Cohort B
    DMD/BMD Female non-carriers controls who have/had an affected child (n=50)
    Intervention: Genetic: Genetic characterization
  • Cohort C
    Healthy Age-Matched Controls (n=50)
    Intervention: Genetic: Genetic characterization
  • Cohort D
    DMD/BMD Female Carriers with no affected children (n=25)
    Intervention: Genetic: Genetic characterization
Publications * Mah ML, Cripe L, Slawinski MK, Al-Zaidy SA, Camino E, Lehman KJ, Jackson JL, Iammarino M, Miller N, Mendell JR, Hor KN. Duchenne and Becker muscular dystrophy carriers: Evidence of cardiomyopathy by exercise and cardiac MRI testing. Int J Cardiol. 2020 Oct 1;316:257-265. doi: 10.1016/j.ijcard.2020.05.052. Epub 2020 May 27.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: November 21, 2016)
250
Original Estimated Enrollment Same as current
Estimated Study Completion Date December 2025
Estimated Primary Completion Date December 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Age >18 years
  • Cohort A requires a genetically confirmed mutation in the DMD gene with an affected child
  • Cohort B includes DMD/BMD mothers with NO somatic mutation in the DMD gene
  • Cohort C age-matched healthy controls with a normal CK level
  • Cohort D requires a genetically confirmed mutation in the DMD gene without an affected child
  • Able to complete testing in English
  • Able to consent

Exclusion Criteria:

  • Subjects with a contraindication to cardiac or skeletal muscle MRI
  • Subjects on heart failure medication at time of enrollment
  • Subjects on steroid treatment
  • Presence of an inherited neurologic disease or comorbidity that may affect their ability to complete this study
  • Has a medical condition or extenuating circumstance that, in the opinion of the investigator, might compromise the subject's ability to comply with the protocol required testing or procedures or compromise the subject's wellbeing, safety, or clinical interpretability
Sex/Gender
Sexes Eligible for Study: Female
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts
Contact: Kate Kanwar, MS 614-355-5649 Kate.Kanwar@nationwidechildrens.org
Contact: Victoria Shay, MS 615-355-5819 Victoria.Shay@nationwidechildrens.org
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT02972580
Other Study ID Numbers IRB16-00319
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Current Responsible Party May Ling Mah, Nationwide Children's Hospital
Original Responsible Party Samiah Al-Zaidy, Nationwide Children's Hospital, Physician/Assistant Professor- Department of Pediatrics
Current Study Sponsor Nationwide Children's Hospital
Original Study Sponsor Same as current
Collaborators Parent Project Muscular Dystrophy
Investigators
Principal Investigator: May Ling Mah, MD PI
PRS Account Nationwide Children's Hospital
Verification Date August 2023