Therapeutic Potential for Aldosterone Inhibition in Duchenne Muscular Dystrophy
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|ClinicalTrials.gov Identifier: NCT02354352|
Recruitment Status : Completed
First Posted : February 3, 2015
Last Update Posted : August 21, 2018
|Condition or disease||Intervention/treatment||Phase|
|Duchenne Muscular Dystrophy||Drug: Eplerenone Drug: Spironolactone||Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||52 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Therapeutic Potential for Aldosterone Inhibition in Duchenne Muscular Dystrophy|
|Study Start Date :||January 2015|
|Actual Primary Completion Date :||May 2018|
|Actual Study Completion Date :||May 2018|
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.
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.
26 Subjects will take Spironolactone, one 50mg capsule by mouth once daily for 12 months.
Other Name: Aldactone
- Left ventricular strain (a sensitive measurement of heart function using cardiac MRI) [ Time Frame: 12 months ]a sensitive measurement of heart function using cardiac MRI
- Forced vital capacity (a measure of pulmonary function) [ Time Frame: 12 months ]a measure of pulmonary function
- muscle injury blood biomarkers (blood measures of muscle damage and repair) [ Time Frame: 12 months ]blood measures of muscle damage and repair
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02354352
|United States, California|
|Mattel Children's Hospital and David Geffen School of Medicine at UCLA|
|Los Angeles, California, United States, 90095-1743|
|United States, Colorado|
|University of Colorado|
|Aurora, Colorado, United States, 80045|
|United States, Kansas|
|University of Kansas Medical Center|
|Kansas City, Kansas, United States, 66103|
|United States, Ohio|
|The Ohio State University Medical Center|
|Columbus, Ohio, United States, 43210|
|United States, Tennessee|
|Vanderbilt University Medical Center|
|Nashville, Tennessee, United States, 37212|
|United States, Utah|
|University of Utah|
|Salt Lake City, Utah, United States, 84113|
|Principal Investigator:||Subha V Raman, MD||Ohio State University|