Clinical trial NCT02972580: 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)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Duchenne Muscular Dystrophy
Becker Muscular Dystrophy
Lead sponsor: Nationwide Children's Hospital
Sponsor class: OTHER
Collaborators: name: Parent Project Muscular Dystrophy
First posted: 2016-11-23
Enrollment: 250
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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)

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.

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

Primary outcomes:
measure: Compromise of cardiac function based on Cardiac Magnetic Resonance Imaging
timeFrame: 2 years
Secondary outcomes:
measure: Cardiac Function Assessment Treadmill SVO2
timeFrame: 2 years
measure: Physical Therapy Assessments Maximum Voluntary Isometric Contraction Testing
timeFrame: 2 Years
measure: Physical Therapy Assessments 6 Minute Walk Test
timeFrame: 2 years
measure: Physical Therapy Assessments ACTIVE-seated
timeFrame: 2 Years
measure: Physical Therapy Assessments Time-to-Rise
timeFrame: 2 Years
measure: Laboratory biomarkers - Creatine Kinase
timeFrame: 2 Years
measure: Laboratory biomarkers - C-Reactive Protein
timeFrame: 2 Years
measure: Laboratory biomarkers - Interleukin-6
timeFrame: 2 Years
measure: Laboratory biomarkers - Cortisol levels
timeFrame: 2 Years
measure: Cognitive Assessment
timeFrame: 2 Years
measure: Caregiver Stress
timeFrame: 2 Years
measure: Pulmonary function testing (PFTs)
timeFrame: 2 Years
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Nationwide Children's Hosptial
state: Ohio
Study officials:
affiliation: PI
name: May Ling Mah, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.