Assessment of Cardiopulmonary Function in Duchenne Muscular Dystrophy (CPI)

This study seeks to develop and validate non-invasive assessments of cardiac and respiratory muscles with magnetic resonance imaging (MRI) to better predict the natural disease progression of Duchenne muscular dystrophy (DMD) in affected individuals over time, as well as determine whether peripheral skeletal muscle dysfunction can predict cardiopulmonary dysfunction. The central hypothesis is that non-invasive MRI measures of the heart, muscle, and peripheral skeletal muscles can sensitively predict future cardiopulmonary decline.

Study Overview

• Status: Completed
• Conditions: Muscular Dystrophy, Duchenne
• Intervention / Treatment: Other: Magnetic Resonance Imaging (MRI); Other: Pulmonary Function Testing (PFT); Other: Metabolic Exercise Testing using stationary bicycle; Other: Echocardiogram

Detailed Description

Magnetic Resonance Imaging (MRI) of the heart and breathing muscles, special breathing tests (called pulmonary function testing), special exercise tests (using a stationary bike), and possibly an echocardiogram (ultrasound of the heart, commonly known as an "echo") will be completed up to 4 times per year for up to 4 years. Most participants will complete testing once or twice each year; however, some participants will be asked to repeat some of the tests twice during each visit.

• Study Type: Observational
• Enrollment (Actual): 9

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • Clinical and Translational Research Building

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 13 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

As the focus of this study is on validating novel measures of cardiac and respiratory function in individuals with DMD, this study will utilize a single-group design with up to 60 males with DMD between 5 and 15 years old upon entry to the study. The participant selection is limited to children since the detrimental effects of DMD begin in early childhood, and the life expectancy of these boys is shortened to the early- to mid-20s. Only males will be eligible to participate in the study because DMD is an X-linked recessive genetic disorder that only leads to the characteristic disease in males. Although females may be carriers, they do not exhibit the same phenotype as males.

Description

Inclusion Criteria:

• Male
• 5-15 years old at the time of enrollment
• Diagnosed with DMD (as defined by parent project)
• Written parental informed consent (and assent where appropriate) before any study procedures take place

Exclusion Criteria:

• Contraindication to an MRI examination
• Presence of a secondary condition that impacts muscle function or metabolism, that leads to developmental delay or impaired motor control, or that is not stable
• Participant is unable to comply with study requirements
• Congenital structural abnormality of the heart, repaired or unrepaired
• Clinically contraindicated participation

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Individuals with DMD; Magnetic Resonance Imaging is a non-invasive method to determine ventricular size, volumes, mass, and ejection fraction. Pulmonary Function testing (PFT) are a series of non-invasive breathing tests that characterize respiratory muscle function, as well as lung compliance and physiology. Metabolic exercise testing using stationary bicycle (exercise capacity and MVO2) evaluates global cardiopulmonary functional status. Echocardiogram with multiple-echo Dixon method helps to assess cross-sectional and longitudinal variations in myocardial structure.

Other: Magnetic Resonance Imaging (MRI); It is a non-invasive method to determine ventricular size, volumes, mass, and ejection fraction.; Other: Pulmonary Function Testing (PFT); It is non-invasive breathing tests that characterize respiratory muscle function, as well as lung compliance and physiology.; Other: Metabolic Exercise Testing using stationary bicycle; Metabolic exercise testing, including assessment of exercise capacity and MVO2, evaluates global cardiopulmonary functional status. This is performed with the use of a stationary bicycle.; Other: Echocardiogram; The echocardiogram performed with the multiple-echo Dixon method helps to assess participants cross-sectionally and longitudinally for variations and changes in myocardial structure.; Other Names: Multiple-echo Dixon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Magnetic Resonance (MRI) T2 and Magnetic Resonance Spectroscopy (MRS)	The MRI T2 and MRS will be used as a noninvasive marker of myocardial damage/inflammation of participants of this study as an early detection for DMD.	up to 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary Function Testing (PFT)	Non-invasive breathing tests that characterize respiratory muscle function, as well as lung compliance and physiology.	up to 4 years
Metabolic Exercise Testing (exercise capacity and MVO2)	With the use of metabolic exercise testing, the aim is to correlate changes in cardiopulmonary function with decline in peripheral skeletal muscle function in individuals with DMD. Metabolic exercise testing includes measuring exercise capacity and maximum oxygen consumption (MVO2).	up to 4 years
Multiple-echo Dixon	The echocardiogram performed with the multiple-echo Dixon method helps to assess participants cross-sectionally and longitudinally for variations and changes in myocardial structure. This method and MRS will also be used for fat fraction determination.	up to 4 years

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: CureDuchenne
• Investigators: Principal Investigator: Barry Byrne, MD, PhD, University of Florida

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): March 6, 2019
• Study Completion (Actual): March 6, 2019

Study Registration Dates

• First Submitted: July 17, 2014
• First Submitted That Met QC Criteria: July 17, 2014
• First Posted (Estimate): July 21, 2014

Study Record Updates

• Last Update Posted (Actual): July 8, 2019
• Last Update Submitted That Met QC Criteria: July 3, 2019
• Last Verified: July 1, 2019

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: IRB201300420

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No