Trial record 16 of 35 for:    eplerenone | Open Studies

Therapeutic Potential for Aldosterone Inhibition in Duchenne Muscular Dystrophy

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2015 by Ohio State University
Sponsor:
Collaborators:
University of California, Los Angeles
University of Utah
University of Colorado, Denver
Information provided by (Responsible Party):
Subha Raman, Ohio State University
ClinicalTrials.gov Identifier:
NCT02354352
First received: January 27, 2015
Last updated: February 23, 2015
Last verified: February 2015
  Purpose

The study is to demonstrate non-inferiority of spironolactone vs. eplerenone in preserving cardiac and pulmonary function in patients with preserved LV ejection fraction. Males with Duchenne muscular dystrophy (DMD) confirmed clinically and by mutation analysis will be enrolled. Subjects must also be non-ambulatory and not taking corticosteroids at the time of enrollment. Subjects will be randomized to either eplerenone or spironolactone. Subjects will use a drug diary to record daily compliance of taking the study medication as well as any concerns they may have during the study period. Subjects will undergo cardiac magnetic resonance imaging (CMR) and pulmonary function tests (PFT) at baseline and then again at 12 months post enrollment. Subjects will also complete a quality of life questionnaire at baseline and 12 months. Degree of elbow contracture will be measured using a goniometer at baseline and 12 months.


Condition Intervention Phase
Duchenne Muscular Dystrophy
Drug: Eplerenone
Drug: Spironolactone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Therapeutic Potential for Aldosterone Inhibition in Duchenne Muscular Dystrophy

Resource links provided by NLM:


Further study details as provided by Ohio State University:

Primary Outcome Measures:
  • Left ventricular strain (a sensitive measurement of heart function using cardiac MRI) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    a sensitive measurement of heart function using cardiac MRI


Secondary Outcome Measures:
  • Forced vital capacity (a measure of pulmonary function) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    a measure of pulmonary function


Other Outcome Measures:
  • muscle injury blood biomarkers (blood measures of muscle damage and repair) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    blood measures of muscle damage and repair


Estimated Enrollment: 52
Study Start Date: January 2015
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Eplerenone
Eplerenone is an aldosterone antagonist used as an adjunct in the management of chronic heart failure. It is marketed under the trade name Inspra. Eplerenone is a potassium-sparing diuretic.
Drug: Eplerenone
26 Subjects will take Eplerenone, one 50mg capsule by mouth once daily for 12 months.
Other Name: Inspra
Active Comparator: Spironolactone
Spironolactone is an aldosterone antagonist used as an adjunct in the management of chronic heart failure. It is marketed under the trade name Aldactone. Spironolactone is a potassium-sparing diuretic.
Drug: Spironolactone
26 Subjects will take Spironolactone, one 50mg capsule by mouth once daily for 12 months.
Other Name: Aldactone

Detailed Description:

DMD is an X-linked disorder in which the sarcolemmal protein dystrophin is effectively absent. Males with DMD typically die in the third and fourth decades of life of cardiopulmonary disease. Mouse models of DMD, autopsy data, and in vivo human studies using magnetic resonance-based late gadolinium enhancement imaging (LGE) have shown that progressive myocardial damage is well underway before left ventricular ejection fraction (LV EF) becomes abnormal.

Exertional symptoms and signs of myocardial disease are typically absent as skeletal muscle disease progressively limits functional capacity in affected boys. Thus, cardiac involvement can go undetected until LV dysfunction and myocardial fibrosis are advanced. While echocardiography remains a useful tool to evaluate LV dysfunction, CMR with LGE is advantageous for DMD patients since it identifies myocardial injury before decline in EF is apparent by echocardiography. Further, greater reproducibility affords efficient sample sizes for cardiomyopathy clinical trials in patients with rare diseases. CMR's increasing availability at DMD clinical centers has afforded earlier cardiomyopathy detection, and has helped refine current management to typically include agents such as angiotensin converting enzyme inhibitors (ACEI) once damage is evident. This strategy, however, may not be sufficient, with prior studies showing decline in systolic function with or without ACEI or angiotensin receptor blocker (ARB) therapy.

The investigators previously tested mineralocorticoid receptor antagonism (MRA) added to ACEI while EF was still normal in a mouse model that mimics the myocardial damage seen in DMD patients. This combination significantly reduced myocardial injury and improved (made more negative) LV circumferential strain (Ecc), a sensitive and early marker of LV systolic dysfunction. Additionally, preliminary findings from a recently completed clinical trial suggests efficacy of eplerenone vs. placebo, while further preclinical data suggests greater benefit without concomitant steroid use. Thus, a non-inferiority trial comparing MRAs is needed.

  Eligibility

Ages Eligible for Study:   10 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Boys age ≥10 years with DMD confirmed clinically and by mutation analysis able to undergo cardiac magnetic resonance (CMR) without sedation
  • LV EF ≥45% by clinically-acquired echocardiography, nuclear scan or cardiac MRI done within 2 weeks of enrollment
  • non-ambulatory

Exclusion Criteria:

  • Non-MR compatible implants
  • Severe claustrophobia
  • Gadolinium contrast allergy
  • Kidney disease
  • Prior use of or allergy to aldosterone antagonist
  • Use of other investigational therapy.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02354352

Contacts
Contact: Subha V Raman, MD 614-293-8963 raman.1@osu.edu
Contact: Beth McCarthy, BSRT(R) 614-688-8020 beth.mccarthy@osumc.edu

Locations
United States, California
Mattel Children's Hospital and David Geffen School of Medicine at UCLA Not yet recruiting
Los Angeles, California, United States, 90095-1743
Contact: Nancy Halnon, MD    310-267-7667    nhalnon@mednet.ucla.edu   
Contact: Vanessa DePaz    310-267-7618    vdepaz@mednet.ucla.edu   
Principal Investigator: Nancy Halnon, MD         
United States, Colorado
University of Colorado Not yet recruiting
Aurora, Colorado, United States, 80045
Contact: Scott Auerbach, MD    720-777-3218    scott.auerbach@childrenscolorado.org   
Contact: Alison Ballard, PNP    720-777-8723    alison.ballard@childrenscolorado.org   
United States, Ohio
The Ohio State University Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Beth McCarthy, BSRT(R)(CV)    614-688-8020    beth.mccarthy@osumc.edu   
Contact: Subha V Raman, MD, MSEE    614-293-8963    raman.1@osu.edu   
Principal Investigator: Subha V Raman, MD         
Sub-Investigator: Linda H Cripe, MD         
United States, Utah
University of Utah Not yet recruiting
Salt Lake City, Utah, United States, 84113
Contact: Michael Puchalski, MD    801-213-7652    michael.puchalski@hsc.utah.edu   
Contact: Ashley Snyder    801-587-9104    ashley.snyder@hsc.utah.edu   
Sponsors and Collaborators
Ohio State University
University of California, Los Angeles
University of Utah
University of Colorado, Denver
Investigators
Principal Investigator: Subha V Raman, MD Ohio State University
  More Information

No publications provided

Responsible Party: Subha Raman, Professor of Medicine, Ohio State University
ClinicalTrials.gov Identifier: NCT02354352     History of Changes
Other Study ID Numbers: 2014H0387
Study First Received: January 27, 2015
Last Updated: February 23, 2015
Health Authority: United States: Food and Drug Administration
United States: Data and Safety Monitoring Board

Additional relevant MeSH terms:
Eplerenone
Muscular Dystrophies
Muscular Dystrophy, Duchenne
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Muscular Diseases
Muscular Disorders, Atrophic
Musculoskeletal Diseases
Nervous System Diseases
Neuromuscular Diseases
Diuretics, Potassium Sparing
Sodium Channel Blockers
Spironolactone
Cardiovascular Agents
Diuretics
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Membrane Transport Modulators
Mineralocorticoid Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on May 28, 2015