Duchenne Muscular DystrophyPhase 3NCT02354352
Therapeutic Potential for Aldosterone Inhibition in Duchenne Muscular Dystrophy
A Phase 3 study testing Eplerenone and Spironolactone in people with Duchenne Muscular Dystrophy, run by Ohio State University at 6 sites in United States.
Trial summary
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. 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 and Spironolactone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 6 sitesUnited States
- Study dates
- 20 Mar 2015to May 2018
- Phase
- Phase 3
- 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
- Boys age ≥7 years with DMD confirmed clinically and by mutation analysis able to undergo cardiac magnetic resonance (CMR) without sedation
- LV EF ≥45% (+/-5%) by clinically-acquired echocardiography, nuclear scan or cardiac MRI done within 2 weeks of enrollment
Who cannot join
- Non-MR compatible implants
- Severe claustrophobia
- Gadolinium contrast allergy
- Kidney disease
- Prior use of or allergy to aldosterone antagonist
- Use of other investigational therapy.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
University of Colorado
Aurora, Colorado, 80045
The Ohio State University Medical Center
Columbus, Ohio, 43210
University of Kansas Medical Center
Kansas City, Kansas, 66103
Mattel Children's Hospital and David Geffen School of Medicine at UCLA
Los Angeles, California, 90095-1743
Vanderbilt University Medical Center
Nashville, Tennessee, 37212
University of Utah
Salt Lake City, Utah, 84113
About this study
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 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.
Read the 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.
- Conditions
- Duchenne Muscular Dystrophy
- Being tested
- Eplerenone, Spironolactone
- Medical subject headings
- Muscular Dystrophy, Duchenne
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EplerenoneDrug
Also called Inspra
26 Subjects will take Eplerenone, one 50mg capsule by mouth once daily for 12 months.
SpironolactoneDrug
Also called Aldactone
26 Subjects will take Spironolactone, one 50mg capsule by mouth once daily for 12 months.
| Study group | Role | What they receive |
|---|---|---|
| Eplerenone | Active comparator | 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. Receives: Drug: Eplerenone |
| Spironolactone | Active comparator | 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. Receives: Drug: Spironolactone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Left Ventricular Strain
a sensitive measure of heart muscle function
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2015 (estimated)
- Study start20 Mar 2015
- Primary completionMay 2018
- Study completionMay 2018
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 (1)Papers the sponsor has linked to this study.
- Other trials for Duchenne Muscular DystrophyStudies of the same condition, open and under way.
- More trials run by Ohio State UniversityThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ohio State University
- Sponsor type
- University, hospital or other
- Collaborators
- University of California, Los Angeles, University of Utah, University of Colorado, Denver, University of Kansas Medical Center, Vanderbilt University Medical Center
- Responsible party
- Principal investigator, Subha Raman, Ohio State University
- Investigators
- Subha V Raman, MD, Principal investigator, Ohio State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02354352
- Sponsor's protocol ID
- 2014H0387
- Status last verified
- Sep 2019
- First submitted
- 27 Jan 2015
- Last updated
- 7 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Raman SV, Hor KN, Mazur W, Cardona A, He X, Halnon N, Markham L, Soslow JH, Puchalski MD, Auerbach SR, Truong U, Smart S, McCarthy B, Saeed IM, Statland JM, Kissel JT, Cripe LH. Stabilization of Early Duchenne Cardiomyopathy With Aldosterone Inhibition: Results of the Multicenter AIDMD Trial. J Am Heart Assoc. 2019 Oct;8(19):e013501. doi: 10.1161/JAHA.119.013501. Epub 2019 Sep 24.
PubMed 31549577
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Therapeutic Potential for Aldosterone Inhibition in Duchenne Muscular Dystrophy
- ClinicalTrials.gov ID
- NCT02354352
- Acronym / sponsor ID
- 2014H0387
- Conditions
- Duchenne Muscular Dystrophy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Ohio State UniversityUniversity, hospital or other
- Collaborators
- University of California, Los Angeles, University of Utah, University of Colorado, Denver, University of Kansas Medical Center, Vanderbilt University Medical Center
- Study start
- 20 Mar 2015 (actual)
- Primary completion
- May 2018 (actual)
- Study completion
- May 2018 (actual)
- First posted
- 3 Feb 2015 (estimated)
- Results
- Posted 24 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 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.
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.
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: EplerenoneEplerenone 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. |
| Spironolactone | Active comparator | Drug: SpironolactoneSpironolactone 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. |
Who may qualify
- Ages
- 7 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Boys age ≥7 years with DMD confirmed clinically and by mutation analysis able to undergo cardiac magnetic resonance (CMR) without sedation
- LV EF ≥45% (+/-5%) by clinically-acquired echocardiography, nuclear scan or cardiac MRI done within 2 weeks of enrollment
Key exclusion criteria (6 listed)
- Non-MR compatible implants
- Severe claustrophobia
- Gadolinium contrast allergy
- Kidney disease
- Prior use of or allergy to aldosterone antagonist
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 |
|---|---|---|
| EplerenoneAlso: Inspra26 Subjects will take Eplerenone, one 50mg capsule by mouth once daily for 12 months. | Drug | Eplerenone |
| SpironolactoneAlso: Aldactone26 Subjects will take Spironolactone, one 50mg capsule by mouth once daily for 12 months. | Drug | Spironolactone |
Primary outcome
Left Ventricular Strain
Time frame: 12 months
a sensitive measure of heart muscle function
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31549577Raman SV, Hor KN, Mazur W, Cardona A, He X, Halnon N, Markham L, Soslow JH, Puchalski MD, Auerbach SR, Truong U, Smart S, McCarthy B, Saeed IM, Statland JM, Kissel JT, Cripe LH. Stabilization of Early Duchenne Cardiomyopathy With Aldosterone Inhibition: Results of the Multicenter AIDMD Trial. J Am Heart Assoc. 2019 Oct;8(19):e013501. doi: 10.1161/JAHA.119.013501. Epub 2019 Sep 24.
- Individual participant dataSharing planned: No
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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 principal investigator
Ohio State University
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Eplerenone and Spironolactone in people with Duchenne Muscular Dystrophy, run by Ohio State University at 6 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 2 inclusion and 6 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 7 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Sep 2019). 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?
Left Ventricular Strain (time frame: 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 NCT02354352, which also lists 1 linked publication.
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 7 Oct 2019.