Duchenne Muscular DystrophyE-SCAR DMDNCT01521546
Eplerenone for Subclinical Cardiomyopathy in Duchenne Muscular Dystrophy
A study testing eplerenone in people with Duchenne Muscular Dystrophy, run by Subha Raman at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 7 years and older, men only
- Conditions the study is for
- Duchenne Muscular Dystrophy
- What is being tested?
- eplerenone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 3 sitesUnited States
- Study dates
- Feb 2012to Jun 2016
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 years and older
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio
The Ohio State University Medical Center
Columbus, Ohio, 43210
Mattel Children's Hospital and David Geffen School of Medicine at UCLA
Los Angeles, California, 90095-1743
About this study
Official title: Early Treatment With Aldosterone Antagonism Attenuates Cardiomyopathy in Duchenne Muscular Dystrophy
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.
Read the detailed description
Duchenne Muscular dystrophy (DMD) is a deadly X-linked disease affecting 1 in 3,500 males. DMD patients suffer significant disability due to skeletal myopathy and excess death due to cardiomyopathy. Current guidelines advocate initiating cardioprotective treatment with evident global cardiac dysfunction, yet this treatment paradigm has not improved survival much beyond the third decade of life. Potentially promising approaches like gene therapy will take considerable time to improve outcomes. Recently completed studies in a DMD mouse model at our institution indicate that existing drugs known as aldosterone antagonists, typically reserved for advanced heart failure patients, preserve skeletal and cardiac muscle function at 80% of normal. Clinical studies at many centers including ours have shown that high-resolution, noninvasive cardiac magnetic resonance (CMR) detects subclinical myocardial fibrosis and abnormal regional function prior to global functional abnormalities. Combining findings from these preclinical and clinical studies, we plan to execute a randomized, controlled clinical trial (RCT) of eplerenone plus background therapy vs. background therapy alone in patients with DMD. We expect that the aldosterone antagonist eplerenone compared to standard therapy significantly delays progressive cardiomyopathy and skeletal myopathy using highly reproducible imaging biomarkers selected for efficient sample size design, to ultimately reduce disability and death.
- Conditions
- Duchenne Muscular Dystrophy
- Being tested
- eplerenone, placebo
- Keywords
- Duchenne muscular dystrophy, cardiomyopathy, aldosterone antagonist
- Medical subject headings
- Muscular Dystrophy, Duchenne, Cardiomyopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
eplerenoneDrug
25mg tablet, once daily by mouth for 12 months
placeboDrug
one tablet by mouth daily for 12 months
| Study group | Role | What they receive |
|---|---|---|
| eplerenone | Active comparator | active study drug Receives: Drug: eplerenone |
| sugar pill | Placebo comparator | placebo Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
12-month Change in Myocardial Strain
a sensitive measurement of heart function using cardiac MRI, change was 12 months minus baseline.
Measured: baseline and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2012 (estimated)
- Study startFeb 2012
- Primary completionJun 2016
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Duchenne Muscular DystrophyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Subha Raman
- Sponsor type
- University, hospital or other
- Collaborators
- Ballou Skies
- Responsible party
- Sponsor-investigator, Subha Raman, Ohio State University
- Investigators
- Subha V Raman, MD, MSEE, Principal investigator, Ohio State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01521546
- Sponsor's protocol ID
- 2011H0251
- Acronym
- E-SCAR DMD
- Status last verified
- Oct 2016
- First submitted
- 26 Jan 2012
- Last updated
- 8 Nov 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 28219442Raman 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.
PubMed 25554404
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Treatment With Aldosterone Antagonism Attenuates Cardiomyopathy in Duchenne Muscular Dystrophy
- ClinicalTrials.gov ID
- NCT01521546
- Acronym / sponsor ID
- E-SCAR DMD / 2011H0251
- Conditions
- Duchenne Muscular Dystrophy
- Keywords
- Duchenne muscular dystrophy, cardiomyopathy, aldosterone antagonist
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Subha RamanUniversity, hospital or other
- Collaborators
- Ballou Skies
- Study start
- Feb 2012
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 30 Jan 2012 (estimated)
- Results
- Posted 27 May 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Duchenne Muscular dystrophy (DMD) is a deadly X-linked disease affecting 1 in 3,500 males. DMD patients suffer significant disability due to skeletal myopathy and excess death due to cardiomyopathy. Current guidelines advocate initiating cardioprotective treatment with evident global cardiac dysfunction, yet this treatment paradigm has not improved survival much beyond the third decade of life. Potentially promising approaches like gene therapy will take considerable time to improve outcomes. Recently completed studies in a DMD mouse model at our institution indicate that existing drugs known as aldosterone antagonists, typically reserved for advanced heart failure patients, preserve skeletal and cardiac muscle function at 80% of normal. Clinical studies at many centers including ours have shown that high-resolution, noninvasive cardiac magnetic resonance (CMR) detects subclinical myocardial fibrosis and abnormal regional function prior to global functional abnormalities. Combining findings from these preclinical and clinical studies, we plan to execute a randomized, controlled clinical trial (RCT) of eplerenone plus background therapy vs. background therapy alone in patients with DMD. We expect that the aldosterone antagonist eplerenone compared to standard therapy significantly delays progressive cardiomyopathy and skeletal myopathy using highly reproducible imaging biomarkers selected for efficient sample size design, to ultimately reduce disability and death.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| eplerenone | Active comparator | Drug: eplerenoneactive study drug |
| sugar pill | Placebo comparator | Drug: placeboplacebo |
Who may qualify
- Ages
- 7 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- 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)
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| eplerenone25mg tablet, once daily by mouth for 12 months | Drug | eplerenone |
| placeboone tablet by mouth daily for 12 months | Drug | sugar pill |
Primary outcome
12-month Change in Myocardial Strain
Time frame: baseline and 12 months
a sensitive measurement of heart function using cardiac MRI, change was 12 months minus baseline.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28219442Raman 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.
- Derived from this study: PubMed 25554404Raman 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Subha V Raman, MD, MSEE principal investigator
Ohio State University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing eplerenone in people with Duchenne Muscular Dystrophy, run by Subha Raman at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 May 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
12-month Change in Myocardial Strain (time frame: baseline and 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01521546, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2016.