Eplerenone for Subclinical Cardiomyopathy in Duchenne Muscular Dystrophy

NCT01521546 | Completed Results DMC

• 1 other identifier: 2011H0251
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 3

Brief Summary

Duchenne muscular dystrophy (DMD), the most common muscular dystrophy, leads to skeletal and cardiac muscle damage. Treatment of pulmonary complications has improved survival; however, heart muscle disease or cardiomyopathy has emerged as a leading cause of death, typically by the third decade. Although myocardial changes begin early, clinically significant heart disease is rarely detected in the first decade of life. Consequently, DMD cardiomyopathy frequently goes unrecognized (and untreated) until advanced (and irreversible). Current DMD cardiovascular care guidelines recommend beta-blockers and angiotensin converting enzyme inhibitors (ACEIs) when decreased ejection fraction (EF) is noted by echocardiography (echo); however, this strategy has not significantly improved outcomes. Our team has recently made a breakthrough in a mouse study, showing in a model that causes the same heart muscle disease in humans with DMD adding an old medicine traditionally used for high blood pressure and late-stage heart failure can actually prevent heart muscle damage. Because of this drug's proven safety in both children and adults, it is ready to be studied immediately in an RCT in patients with DMD to hopefully show, as we did in mice, that we can prevent the devastating consequences of heart muscle damage.

Conditions

Duchenne Muscular Dystrophy

Keywords

Duchenne muscular dystrophy; cardiomyopathy; aldosterone antagonist

Outcome Measures

Primary Outcomes (1)

• 12-month Change in Myocardial Strain

  a sensitive measurement of heart function using cardiac MRI, change was 12 months minus baseline.

  baseline and 12 months

Study Arms (2)

eplerenone

ACTIVE COMPARATOR

active study drug

Drug: eplerenone

sugar pill

PLACEBO COMPARATOR

placebo

Drug: placebo

Interventions

eplerenone DRUG

25mg tablet, once daily by mouth for 12 months

eplerenone

placebo DRUG

one tablet by mouth daily for 12 months

sugar pill

Eligibility Criteria

• Age: 7 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• DMD patients age 7 years and older (and able to complete cardiac MRI without sedation) with preserved left ventricular (LV) systolic function and abnormal heart muscle by late post-gadolinium imaging (LGE)

You may not qualify if:

• renal insufficiency (GFR \<40 mL/min/m2)
• non-MR compatible implants (e.g. neurostimulator, AICD)
• severe claustrophobia
• allergy to gadolinium contrast
• prior use of or known allergy to epleronone
• use of potassium-sparing diuretics
• serum potassium level of \>5.0 mmol/L

Sponsors & Collaborators

• Subha Raman: lead
• Ballou Skies: collaborator

Study Sites (3)

Mattel Children's Hospital and David Geffen School of Medicine at UCLA

Los Angeles, California, 90095-1743, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Location

The Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Related Publications (2)

• Raman SV, Hor KN, Mazur W, He X, Kissel JT, Smart S, McCarthy B, Roble SL, Cripe LH. Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: results of a two-year open-label extension trial. Orphanet J Rare Dis. 2017 Feb 20;12(1):39. doi: 10.1186/s13023-017-0590-8.

  PMID: 28219442 DERIVED

• Raman SV, Hor KN, Mazur W, Halnon NJ, Kissel JT, He X, Tran T, Smart S, McCarthy B, Taylor MD, Jefferies JL, Rafael-Fortney JA, Lowe J, Roble SL, Cripe LH. Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2015 Feb;14(2):153-61. doi: 10.1016/S1474-4422(14)70318-7. Epub 2014 Dec 30.

  PMID: 25554404 DERIVED

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne; Cardiomyopathies

Interventions

Eplerenone

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Subha V. Raman, MD
• Organization: The Ohio State University

raman.1@osu.edu

(614)293-8963

Study Officials

• Subha V Raman, MD, MSEE

  Ohio State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: January 26, 2012
• First Posted: January 30, 2012
• Study Start: February 1, 2012
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: November 8, 2016
• Results First Posted: May 27, 2015

Record last verified: 2016-10

Locations

US (3)