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

Characterization of Clinical Skeletal and Cardiac Impairment in Carriers of Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD)

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.

Study Overview

• Status: Recruiting
• Conditions: Duchenne Muscular Dystrophy; Becker Muscular Dystrophy
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Estimated): 250

Contacts and Locations

• Study Contact: Name: Kate Kanwar, MS; Phone Number: 614-355-5649; Email: Kate.kanwar@nationwidechildrens.org
• Study Contact Backup: Name: Victoria Shay, MS; Phone Number: 615-355-5819; Email: victoria.shay@nationwidechildrens.org

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Recruiting
      • Nationwide Children's Hosptial
      • Contact: Kate Kanwar, MS; Phone Number: 614-355-5649; Email: Kate.kanwar@nationwidechildrens.org
      • Contact: Victoria Shay, MS; Phone Number: 615-355-5819; Email: victoria.shay@nationwidechildrens.org
      • Principal Investigator: May Ling Mah, MD
      • Sub-Investigator: Jerry Mendell, MD
      • Sub-Investigator: Kan Hor, MD
      • Sub-Investigator: Linda Cripe, MD
      • Sub-Investigator: Jamie Jackson, PhD
      • Sub-Investigator: Lindsay Alfano, DPT
      • Sub-Investigator: Kelly Lehman, CNP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• 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)

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compromise of cardiac function based on Cardiac Magnetic Resonance Imaging	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.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac Function Assessment Treadmill SVO2	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 years
Physical Therapy Assessments Maximum Voluntary Isometric Contraction Testing	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.	2 Years
Physical Therapy Assessments 6 Minute Walk Test	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.	2 years
Physical Therapy Assessments ACTIVE-seated	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.	2 Years
Physical Therapy Assessments Time-to-Rise	A timed-test to measure ability to rise from the floor is quantifiable and measuring over time tells if there is loss of function.	2 Years
Laboratory biomarkers - Creatine Kinase	CK levels are an indicator of muscle breakdown.	2 Years
Laboratory biomarkers - C-Reactive Protein	Pro-inflammatory marker indicating the degree of inflammation of muscle when there is muscle breakdown.	2 Years
Laboratory biomarkers - Interleukin-6	Pro-inflammatory marker indicating the degree of inflammation of muscle when there is muscle breakdown.	2 Years
Laboratory biomarkers - Cortisol levels	Hair cortisol levels measure stress levels as a means of understanding coping with disease.	2 Years
Cognitive Assessment	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.	2 Years
Caregiver Stress	Online self-report survey to assess stress burden on caregiver.	2 Years
Pulmonary function testing (PFTs)	Stable or improved FVC	2 Years

Collaborators and Investigators

• Sponsor: Nationwide Children's Hospital
• Collaborators: Parent Project Muscular Dystrophy
• Investigators: Principal Investigator: May Ling Mah, MD, PI

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: July 25, 2016
• First Submitted That Met QC Criteria: November 21, 2016
• First Posted (Estimated): November 23, 2016

Study Record Updates

• Last Update Posted (Actual): August 31, 2023
• Last Update Submitted That Met QC Criteria: August 29, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: IRB16-00319