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

• ClinicalTrials.gov Identifier: NCT02972580
• Recruitment Status: Unknown
• First Posted: November 23, 2016
• Last Update Posted: July 16, 2020
• Sponsor: Nationwide Children's Hospital
• Collaborator: Parent Project Muscular Dystrophy
• Information provided by (Responsible Party): Jerry R. Mendell, Nationwide Children's Hospital

Study Description

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.

Condition or disease	Intervention/treatment
Duchenne Muscular Dystrophy; Becker Muscular Dystrophy	Genetic: Genetic characterization

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 Design

• Study Type: Observational
• Estimated Enrollment: 250 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Characterization of Clinical Skeletal and Cardiac Impairment in Carriers of Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD)
• Study Start Date: June 2016
• Estimated Primary Completion Date: December 2020
• Estimated Study Completion Date: December 2020

Groups and Cohorts

Group/Cohort	Intervention/treatment
Cohort A; DMD/BMD Female Carriers who have/had an affected child (n=150)	Genetic: Genetic characterization; Confirmatory genetic testing for mutation in DMD gene (Carrier Status) for subjects in respective Cohorts
Cohort B; DMD/BMD Female non-carriers controls who have/had an affected child (n=50)	Genetic: Genetic characterization; Confirmatory genetic testing for mutation in DMD gene (Carrier Status) for subjects in respective Cohorts
Cohort C; Healthy Age-Matched Controls (n=50)	Genetic: Genetic characterization; Confirmatory genetic testing for mutation in DMD gene (Carrier Status) for subjects in respective Cohorts
Cohort D; DMD/BMD Female Carriers with no affected children (n=25)	Genetic: Genetic characterization; Confirmatory genetic testing for mutation in DMD gene (Carrier Status) for subjects in respective Cohorts

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. Laboratory biomarkers - Creatine Kinase [ Time Frame: 2 Years ]
   CK levels are an indicator of muscle breakdown.
7. Laboratory biomarkers - C-Reactive Protein [ Time Frame: 2 Years ]
   Pro-inflammatory marker indicating the degree of inflammation of muscle when there is muscle breakdown.
8. Laboratory biomarkers - Interleukin-6 [ Time Frame: 2 Years ]
   Pro-inflammatory marker indicating the degree of inflammation of muscle when there is muscle breakdown.
9. Laboratory biomarkers - Cortisol levels [ Time Frame: 2 Years ]
   Hair cortisol levels measure stress levels as a means of understanding coping with disease.
10. 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.
11. Caregiver Stress [ Time Frame: 2 Years ]
    Online self-report survey to assess stress burden on caregiver.
12. Pulmonary function testing (PFTs) [ Time Frame: 2 Years ]
    Stable or improved FVC

Biospecimen Retention:   Samples With DNA

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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes
• 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)

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

Contacts and Locations

Locations

United States, Ohio

Nationwide Children's Hosptial

Columbus, Ohio, United States, 43205

Sponsors and Collaborators

Nationwide Children's Hospital

Parent Project Muscular Dystrophy

Investigators

• Principal Investigator: Jerry Mendell, MD; PI

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Jerry R. Mendell, Principal Investigator, Nationwide Children's Hospital
• ClinicalTrials.gov Identifier: NCT02972580
• Other Study ID Numbers: IRB16-00319
• First Posted: November 23, 2016
• Last Update Posted: July 16, 2020
• Last Verified: July 2020

Additional relevant MeSH terms:

Muscular Dystrophies; Muscular Dystrophy, Duchenne; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked