Duchenne Muscular DystrophyPhase 2REVERSE-DBMDNCT01168908
Revatio for Heart Disease in Duchenne Muscular Dystrophy and Becker Muscular Dystrophy
A Phase 2 study testing Sildenafil in people with Duchenne Muscular Dystrophy and Becker Muscular Dystrophy, run by Hugo W. Moser Research Institute at Kennedy Krieger, Inc. at 1 site in United States.
Trial summary
This study, supported by Charley's Fund, Inc., is being done to determine if the drug Revatio®(also known as Sildenafil), as compared to placebo (an inactive substance that looks like the study drug, but contains no medication), improves heart function in people with Duchenne Muscular Dystrophy and Becker Muscular… Read more about this study
- Who is it for?
- Ages 18 to 50 years, men only
- Conditions the study is for
- Duchenne Muscular Dystrophy, Becker Muscular Dystrophy
- What is being tested?
- Sildenafil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2010to Jan 2014
- Phase
- Phase 2
- 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 18 to 50 years
- Men only
- No healthy volunteers
- Adult
Who may be able to join
- DBMD as determined by either a skeletal muscle biopsy demonstrating absence or lack of dystrophin, and/or genetic testing showing a mutation in the dystrophin gene predictive of DBMD, as well as a consistent physical examination
- Male gender
- Age greater than or equal to 18 years
- Cardiac dysfunction with ejection fraction less than or equal to 50% as determined by echocardiogram, cardiac MRI, or multi-gated acquisition (MUGA) scan
- On a stable dose of ACE-inhibitor or angiotensin receptor blocker (ARB) for at least 3 months; beta-adrenergic receptor blockers and glucocorticosteroids are not required but if used, a stable dose for at least 3 months is required.
- Ability of the subject or legal guardian to provide informed consent
- Ability to adhere with study follow-up
- Willingness to abstain from food and alcohol for 8 hours prior to FMD
Who cannot join
- Use of nitrates or alpha-adrenergic receptor blockers
- Known intolerance or allergy to sildenafil, or a history of any severe allergic or anaphylactic reactions
- Any medical or psychosocial condition, which, in the view of the study investigator, makes study participation inadvisable
- Known hereditary retinal disorder such as retinitis pigmentosa
- History of priapism or conditions that may predispose to priapism such as sickle cell anemia, multiple myeloma, or leukemia
- Bleeding disorders
Show all 12Show fewer
- Active tobacco use
- Chronic atrial fibrillation or frequent arrhythmia that would result in an irregular pulse
- Factors that would preclude obtaining an MRI study - (e.g. implantable pacemaker or cardioverter-defibrillator; body habitus cannot fit into scanner)
- Systolic blood pressure (SBP) less than 85 mmHg at baseline evaluation
- Chronic kidney disease stages 4 and 5: GFR< 30 mL/min/1.73 m2 as determined by serum cystatin C level and the equation eGFRcys = 76.7 x (serum cystatin C-1.18)
- Current use of sildenafil.
Trial locations and contacts
1 site in 1 country.
United States1 site
Kennedy Krieger Institute, Johns Hopkins School of Medicine
Baltimore, Maryland, 21205
About this study
Official title: Phase 2 Clinical Trial of Sildenafil for Cardiac Dysfunction in Duchenne Muscular Dystrophy and Becker Muscular Dystrophy
This study, supported by Charley's Fund, Inc., is being done to determine if the drug Revatio®(also known as Sildenafil), as compared to placebo (an inactive substance that looks like the study drug, but contains no medication), improves heart function in people with Duchenne Muscular Dystrophy and Becker Muscular Dystrophy (DBMD).
In people with DBMD, dystrophin is not present or lacking in heart and muscle. This is associated with abnormalities in an enzyme called "neuronal nitric oxide synthase" or nNOS, and leads to decreases in "cyclic GMP," which is necessary for proper function of those muscles. Revatio blocks an enzyme called phosphodiesterase 5 (PDE5), and helps to restore the normal amounts of cyclic GMP. The purpose of this research is to determine if Revatio is safe for people with DBMD and if it can improve heart function.
Hypothesis : PDE5 inhibition, with the use of Revatio, will improve cardiac function in patients with DBMD.
Read the detailed description
This clinical trial is focused on cardiovascular disease due to dystrophin deficiency. Dystrophin is normally localized to the muscle cell membrane where it interacts with a complex of proteins including neuronal nitric oxide synthase (nNOS). DMD gene mutations lead to the loss of dystrophin and to mislocalization and reduced activity of nNOS, consequently reducing cyclic guanosine monophosphate (cGMP) and the activity of its downstream effector, protein kinase G. Our group and others have shown that inhibition of phosphodiesterase 5 (PDE5) leads to favorable cardiac remodeling and improved vascular tone in animal models of heart failure.
This will be a phase 2, randomized, double-blind, placebo-controlled single center study for 6 months followed by open-label period of 6 months in which all enrolled subjects receive Revatio (a PDE5 inhibitor). A single dose of Revatio (20 mg three times daily) will be tested based on the safety and efficacy of that dose for treatment of pulmonary hypertension.
The primary endpoint will be the change in cardiac left ventricular end-systolic volume (LVESV) as determined by cardiac MRI after 6 months of Revatio compared to baseline. A 10% change in LVESV will be considered significant. This degree of improvement has generally been observed in cardiac therapies that improve survival such as ACE inhibitors, beta blockers, and cardiac resynchronization. The change from baseline in LVESV after 6 months of Revatio will be compared to the change in LVESV over 6 months with placebo. The study will extend for an additional 6 months of open-label Revatio to provide data on 6 months versus 12 months of Revatio treatment. Additional secondary endpoints will include differences in systolic and diastolic LV function by MRI, differences in LV mass and fibrosis by MRI, brachial flow-mediated vasodilation (peripheral endothelial function), and targeted exploratory assessment of differences in skeletal muscle function using forced vital capacity (FVC) and pincher and grip testing. Safety will be assessed by differences in the frequency and grade of adverse events
The study is taking place at the Kennedy Krieger Institute/Johns Hopkins Medical Institutions in Baltimore, MD. The trial requires out-patient visits over a 12-month period. Travel funds, through a grant from Ryan's Quest, are available.
- Being tested
- Sildenafil
- Keywords
- Clinical trial, Revatio, Sildenafil, Muscular Dystrophy, Duchenne, Becker, Adult, Adolescent
- Medical subject headings
- Muscular Dystrophy, Duchenne, Muscular Dystrophies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SildenafilDrug
Also called Revatio
20mg tablet three times daily
| Study group | Role | What they receive |
|---|---|---|
| Revatio (sildenafil) | Experimental | This arm will receive Revatio (sildenafil) for 12 months. During the first 6 months, the subject and investigator will be blinded to treatment. The second 6 months, will be open label treatment with Revatio. Receives: Drug: Sildenafil |
| Placebo | Other | This arm will receive placebo (sugar pill) for 6 months and Revatio (sildenafil) for 6 months. During the first 6 months, the subject and investigator will be blinded to treatment. The second 6 months, will be open label treatment with Revatio. Receives: Drug: Sildenafil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Cardiac Left Ventricular End-systolic Volume (LVESV) by Cardiac Magnetic Resonance (CMR) Imaging.
To determine whether a 6 month trial of oral sildenafil compared to placebo improves cardiac contractile function in DBMD as determined by a > 10% decline in end-systolic volume as detected by CMR.
Measured: 6 months compared to baseline
Secondary outcomes (5)
Change in Cardiac Systolic and Diastolic Function by CMR
Cardiac volumes and systolic ejection parameters will be measured.
Measured: 6 months and 12 months
Change in Cardiac Mass
Left ventricular (LV) mass will be measured by CMR .
Measured: 6 months and 12 months
Change in Forced Vital Capacity (FVC) by Pulmonary Function Testing
Skeletal muscle function of the diaphragm will be measured using FVC by pulmonary function testing.
Measured: 6 months and 12 months
Change in Skeletal Muscle Strength
Skeletal muscle strength will be assessed by pincher and grip dynamometry
Measured: 6 months and 12 months
Ejection Fraction
Left ventricular ejection fraction by cardiac MRI was measured
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2010 (estimated)
- Study startSep 2010
- Primary completionJan 2014
- Study completionJan 2014
Why it stopped: As recommended by the DSMB.
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.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
- Sponsor type
- University, hospital or other
- Collaborators
- Johns Hopkins University
- Responsible party
- Principal investigator, Kathryn Wagner, Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
- Investigators
- Daniel P Judge, MD, Principal investigator, Johns Hopkins School of MedicineKathryn R. Wagner, M.D., Ph.D., Principal investigator, The Kennedy Krieger Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01168908
- Sponsor's protocol ID
- NA-00036602
- Acronym
- REVERSE-DBMD
- Status last verified
- Feb 2019
- First submitted
- 22 Jul 2010
- Last updated
- 26 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Leung DG, Herzka DA, Thompson WR, He B, Bibat G, Tennekoon G, Russell SD, Schuleri KH, Lardo AC, Kass DA, Thompson RE, Judge DP, Wagner KR. Sildenafil does not improve cardiomyopathy in Duchenne/Becker muscular dystrophy. Ann Neurol. 2014 Oct;76(4):541-9. doi: 10.1002/ana.24214. Epub 2014 Jul 10.
PubMed 25042693
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Clinical Trial of Sildenafil for Cardiac Dysfunction in Duchenne Muscular Dystrophy and Becker Muscular Dystrophy
- ClinicalTrials.gov ID
- NCT01168908
- Acronym / sponsor ID
- REVERSE-DBMD / NA-00036602
- Keywords
- Clinical trial, Revatio, Sildenafil, Muscular Dystrophy, Duchenne, Becker, Adult, Adolescent
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: As recommended by the DSMB.
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Hugo W. Moser Research Institute at Kennedy Krieger, Inc.University, hospital or other
- Collaborators
- Johns Hopkins University
- Study start
- Sep 2010
- Primary completion
- Jan 2014 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 23 Jul 2010 (estimated)
- Results
- Posted 21 Mar 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study, supported by Charley's Fund, Inc., is being done to determine if the drug Revatio®(also known as Sildenafil), as compared to placebo (an inactive substance that looks like the study drug, but contains no medication), improves heart function in people with Duchenne Muscular Dystrophy and Becker Muscular Dystrophy (DBMD).
In people with DBMD, dystrophin is not present or lacking in heart and muscle. This is associated with abnormalities in an enzyme called "neuronal nitric oxide synthase" or nNOS, and leads to decreases in "cyclic GMP," which is necessary for proper function of those muscles. Revatio blocks an enzyme called phosphodiesterase 5 (PDE5), and helps to restore the normal amounts of cyclic GMP. The purpose of this research is to determine if Revatio is safe for people with DBMD and if it can improve heart function.
Hypothesis : PDE5 inhibition, with the use of Revatio, will improve cardiac function in patients with DBMD.
Detailed description
This clinical trial is focused on cardiovascular disease due to dystrophin deficiency. Dystrophin is normally localized to the muscle cell membrane where it interacts with a complex of proteins including neuronal nitric oxide synthase (nNOS). DMD gene mutations lead to the loss of dystrophin and to mislocalization and reduced activity of nNOS, consequently reducing cyclic guanosine monophosphate (cGMP) and the activity of its downstream effector, protein kinase G. Our group and others have shown that inhibition of phosphodiesterase 5 (PDE5) leads to favorable cardiac remodeling and improved vascular tone in animal models of heart failure.
This will be a phase 2, randomized, double-blind, placebo-controlled single center study for 6 months followed by open-label period of 6 months in which all enrolled subjects receive Revatio (a PDE5 inhibitor). A single dose of Revatio (20 mg three times daily) will be tested based on the safety and efficacy of that dose for treatment of pulmonary hypertension.
The primary endpoint will be the change in cardiac left ventricular end-systolic volume (LVESV) as determined by cardiac MRI after 6 months of Revatio compared to baseline. A 10% change in LVESV will be considered significant. This degree of improvement has generally been observed in cardiac therapies that improve survival such as ACE inhibitors, beta blockers, and cardiac resynchronization. The change from baseline in LVESV after 6 months of Revatio will be compared to the change in LVESV over 6 months with placebo. The study will extend for an additional 6 months of open-label Revatio to provide data on 6 months versus 12 months of Revatio treatment. Additional secondary endpoints will include differences in systolic and diastolic LV function by MRI, differences in LV mass and fibrosis by MRI, brachial flow-mediated vasodilation (peripheral endothelial function), and targeted exploratory assessment of differences in skeletal muscle function using forced vital capacity (FVC) and pincher and grip testing. Safety will be assessed by differences in the frequency and grade of adverse events
The study is taking place at the Kennedy Krieger Institute/Johns Hopkins Medical Institutions in Baltimore, MD. The trial requires out-patient visits over a 12-month period. Travel funds, through a grant from Ryan's Quest, are available.
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 |
|---|---|---|
| Revatio (sildenafil) | Experimental | Drug: SildenafilThis arm will receive Revatio (sildenafil) for 12 months. During the first 6 months, the subject and investigator will be blinded to treatment. The second 6 months, will be open label treatment with Revatio. |
| Placebo | Other | Drug: SildenafilThis arm will receive placebo (sugar pill) for 6 months and Revatio (sildenafil) for 6 months. During the first 6 months, the subject and investigator will be blinded to treatment. The second 6 months, will be open label treatment with Revatio. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- DBMD as determined by either a skeletal muscle biopsy demonstrating absence or lack of dystrophin, and/or genetic testing showing a mutation in the dystrophin gene predictive of DBMD, as well as a consistent physical examination
- Male gender
- Age greater than or equal to 18 years
- Cardiac dysfunction with ejection fraction less than or equal to 50% as determined by echocardiogram, cardiac MRI, or multi-gated acquisition (MUGA) scan
- On a stable dose of ACE-inhibitor or angiotensin receptor blocker (ARB) for at least 3 months; beta-adrenergic receptor blockers and glucocorticosteroids are not required but if used, a stable dose for at least 3 months is required.
Key exclusion criteria (12 listed)
- Use of nitrates or alpha-adrenergic receptor blockers
- Known intolerance or allergy to sildenafil, or a history of any severe allergic or anaphylactic reactions
- Any medical or psychosocial condition, which, in the view of the study investigator, makes study participation inadvisable
- Known hereditary retinal disorder such as retinitis pigmentosa
- History of priapism or conditions that may predispose to priapism such as sickle cell anemia, multiple myeloma, or leukemia
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 |
|---|---|---|
| SildenafilAlso: Revatio20mg tablet three times daily | Drug | Placebo, Revatio (sildenafil) |
Primary outcome
Change in Cardiac Left Ventricular End-systolic Volume (LVESV) by Cardiac Magnetic Resonance (CMR) Imaging.
Time frame: 6 months compared to baseline
To determine whether a 6 month trial of oral sildenafil compared to placebo improves cardiac contractile function in DBMD as determined by a > 10% decline in end-systolic volume as detected by CMR.
5 secondary outcomes
Change in Cardiac Systolic and Diastolic Function by CMR
Time frame: 6 months and 12 months
Change in Cardiac Mass
Time frame: 6 months and 12 months
Change in Forced Vital Capacity (FVC) by Pulmonary Function Testing
Time frame: 6 months and 12 months
Change in Skeletal Muscle Strength
Time frame: 6 months and 12 months
Ejection Fraction
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25042693Leung DG, Herzka DA, Thompson WR, He B, Bibat G, Tennekoon G, Russell SD, Schuleri KH, Lardo AC, Kass DA, Thompson RE, Judge DP, Wagner KR. Sildenafil does not improve cardiomyopathy in Duchenne/Becker muscular dystrophy. Ann Neurol. 2014 Oct;76(4):541-9. doi: 10.1002/ana.24214. Epub 2014 Jul 10.
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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.
Daniel P Judge, MD principal investigator
Johns Hopkins School of Medicine
Kathryn R. Wagner, M.D., Ph.D. principal investigator
The Kennedy Krieger Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sildenafil in people with Duchenne Muscular Dystrophy and Becker Muscular Dystrophy, run by Hugo W. Moser Research Institute at Kennedy Krieger, Inc. at 1 site 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 8 inclusion and 12 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: stopped early, as of the sponsor's last update on 26 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 21 Mar 2018). 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?
Change in Cardiac Left Ventricular End-systolic Volume (LVESV) by Cardiac Magnetic Resonance (CMR) Imaging. (time frame: 6 months compared to baseline). 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 NCT01168908, 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 26 Feb 2019.