Validating Cardiac MRI Biomarkers and Genotype-Phenotype Correlations for DMD

Not Applicable

Completed

• Conditions: Muscular Dystrophy, Duchenne
• Interventions: Other: Cardiac MRI with contrast; Other: Cardiac MRI without contrast; Other: Blood Test; Other: Repeat MRI scan; Other: Heart Rate; Other: Pulmonary Function Test; Other: Genetic Testing

• Registration Number: NCT02834650
• Lead Sponsor: Stanford University

Brief Summary

This study will collect MRI from healthy volunteer boys and boys with Duchenne Muscular Dystrophy (DMD) to help researchers identify and validate cardiac MRI biomarkers to better understand the health of the heart and changes in heart health over time in boys with DMD.

Currently, there is a lack of sufficiently well characterized cardiac MRI biomarkers that can serve as endpoints for detecting on-target and/or off-target cardiac effects during clinical drug trials for boys with DMD.

Consequently, the first objective is to identify and characterize several cardiac MRI biomarkers for boys with DMD.

Detailed Description

The second objective is to use their well-characterized cardiac MRI biomarkers and define their sensitivity for detecting early cardiac involvement. The final objective is to use these validated cardiac MRI biomarkers to better understand the genotype-phenotype correlation in boys with DMD, which to date remain tenuous. The investigators propose a pilot study to explore cardiac genotype-phenotype correlations in boys with DMD and outlier phenotypes using approaches they have pioneered for skeletal muscle.

Study Timeline

• Study First Submitted: 2016-07-13
• Study First Submitted QC: 2016-07-13
• Study First Posted: 2016-07-15
• Study Start: 2017-02-01
• Primary Completion: 2022-03-30
• Study Completion: 2022-03-30
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-04
• Last Update Posted: 2022-05-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 89

Inclusion Criteria

• Healthy boys or pediatric patients with DMD age 7 to 21
• Able & willing to complete an approximately 75-minute (or less) MRI exam without sedation or mechanical ventilation
• Drug regimen (if applicable) stable for at least 3 months prior to participation

Exclusion Criteria

• Renal insufficiency (GFR<40 mL/min/m2)
• Non-MRI compatible implants (e.g. neurostimulator, pacemaker, implanted cardioverter defibrillator)
• Claustrophobia that prevents an MRI exam
• Known allergy to MRI contrast agents
• Serum potassium level of >5.0 mmol/L
• Signs and symptoms of heart failure

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Group 2	Blood Test	Group 2 comprises boys with DMD who will complete a Cardiac MRI with contrast, a blood test, a heart rate test and a pulmonary function test and a repeat MRI scan with contrast at 6 Months.
Group 1b	Cardiac MRI with contrast	Group 1b comprises boys with DMD who will complete a Cardiac MRI with contrast, a blood test, a heart rate test and a pulmonary function test. A subset of boys with DMD will have a repeat MRI with contrast at Children's Hospital of Orange County.
Group 1a	Cardiac MRI without contrast	Group 1a comprises healthy volunteers who will complete a Cardiac MRI without contrast. A subset of healthy volunteers will have a repeat MRI at Children's Hospital of Orange County.
Group 1a	Repeat MRI scan	Group 1a comprises healthy volunteers who will complete a Cardiac MRI without contrast. A subset of healthy volunteers will have a repeat MRI at Children's Hospital of Orange County.
Group 1b	Blood Test	Group 1b comprises boys with DMD who will complete a Cardiac MRI with contrast, a blood test, a heart rate test and a pulmonary function test. A subset of boys with DMD will have a repeat MRI with contrast at Children's Hospital of Orange County.
Group 1b	Genetic Testing	Group 1b comprises boys with DMD who will complete a Cardiac MRI with contrast, a blood test, a heart rate test and a pulmonary function test. A subset of boys with DMD will have a repeat MRI with contrast at Children's Hospital of Orange County.
Group 1b	Heart Rate	Group 1b comprises boys with DMD who will complete a Cardiac MRI with contrast, a blood test, a heart rate test and a pulmonary function test. A subset of boys with DMD will have a repeat MRI with contrast at Children's Hospital of Orange County.
Group 1b	Pulmonary Function Test	Group 1b comprises boys with DMD who will complete a Cardiac MRI with contrast, a blood test, a heart rate test and a pulmonary function test. A subset of boys with DMD will have a repeat MRI with contrast at Children's Hospital of Orange County.
Group 2	Cardiac MRI with contrast	Group 2 comprises boys with DMD who will complete a Cardiac MRI with contrast, a blood test, a heart rate test and a pulmonary function test and a repeat MRI scan with contrast at 6 Months.
Group 2	Heart Rate	Group 2 comprises boys with DMD who will complete a Cardiac MRI with contrast, a blood test, a heart rate test and a pulmonary function test and a repeat MRI scan with contrast at 6 Months.
Group 2	Genetic Testing	Group 2 comprises boys with DMD who will complete a Cardiac MRI with contrast, a blood test, a heart rate test and a pulmonary function test and a repeat MRI scan with contrast at 6 Months.
Group 3	Blood Test	Group 3 comprises boys with DMD who will complete a Cardiac MRI with contrast, a blood test, a heart rate test and a pulmonary function test and a genetic testing.
Group 3	Pulmonary Function Test	Group 3 comprises boys with DMD who will complete a Cardiac MRI with contrast, a blood test, a heart rate test and a pulmonary function test and a genetic testing.
Group 1b	Repeat MRI scan	Group 1b comprises boys with DMD who will complete a Cardiac MRI with contrast, a blood test, a heart rate test and a pulmonary function test. A subset of boys with DMD will have a repeat MRI with contrast at Children's Hospital of Orange County.
Group 3	Genetic Testing	Group 3 comprises boys with DMD who will complete a Cardiac MRI with contrast, a blood test, a heart rate test and a pulmonary function test and a genetic testing.
Group 2	Pulmonary Function Test	Group 2 comprises boys with DMD who will complete a Cardiac MRI with contrast, a blood test, a heart rate test and a pulmonary function test and a repeat MRI scan with contrast at 6 Months.
Group 2	Repeat MRI scan	Group 2 comprises boys with DMD who will complete a Cardiac MRI with contrast, a blood test, a heart rate test and a pulmonary function test and a repeat MRI scan with contrast at 6 Months.
Group 3	Cardiac MRI with contrast	Group 3 comprises boys with DMD who will complete a Cardiac MRI with contrast, a blood test, a heart rate test and a pulmonary function test and a genetic testing.
Group 3	Heart Rate	Group 3 comprises boys with DMD who will complete a Cardiac MRI with contrast, a blood test, a heart rate test and a pulmonary function test and a genetic testing.

Primary Outcome Measures

Name	Time	Method
Myocardial Functional Characterization	6 months	Strain imaging and rotational mechanics
Genomic Analysis	4 years	Proposing mechanisms of cardiac dysfunction or protective phenotypes using genomic analysis
Myocardial Tissue Characterization	6 months	Focal and diffuse fibrosis, intra myocardial fat, edema plus water mobility

Trial Locations

Locations (3)

Stanford University; 🇺🇸 Stanford, California, United States

University of California, Los Angeles; 🇺🇸 Los Angeles, California, United States

Children's Hospital of Orange County; 🇺🇸 Orange, California, United States