Revatio for Heart Disease in Duchenne Muscular Dystrophy and Becker Muscular Dystrophy

NCT01168908 | Terminated Phase 2 Results DMC

• 1 other identifier: NA-00036602
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Duchenne Muscular Dystrophy; Becker Muscular Dystrophy

Keywords

Clinical trial; Revatio; Sildenafil; Muscular Dystrophy; Duchenne; Becker; Adult; Adolescent

Outcome Measures

Primary Outcomes (1)

• 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.

  6 months compared to baseline

Secondary Outcomes (5)

• Change in Cardiac Systolic and Diastolic Function by CMR

  6 months and 12 months

• Change in Cardiac Mass

  6 months and 12 months

• Change in Forced Vital Capacity (FVC) by Pulmonary Function Testing

  6 months and 12 months

• Change in Skeletal Muscle Strength

  6 months and 12 months

• Ejection Fraction

  6 months

Study Arms (2)

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.

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.

Drug: Sildenafil

Interventions

Sildenafil DRUG

20mg tablet three times daily

Also known as: Revatio

Placebo; Revatio (sildenafil)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Hugo W. Moser Research Institute at Kennedy Krieger, Inc.: lead
• Johns Hopkins University: collaborator

Study Sites (1)

Kennedy Krieger Institute, Johns Hopkins School of Medicine

Baltimore, Maryland, 21205, United States

Location

Related Publications (1)

• 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.

  PMID: 25042693 DERIVED

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne; Muscular Dystrophies

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Kathryn Wagner, MD, PhD
• Organization: Kennedy Krieger Institute

wagnerk@kennedykrieger.org

443-923-9525

Study Officials

• Daniel P Judge, MD

  Johns Hopkins School of Medicine

  PRINCIPAL INVESTIGATOR

• Kathryn R. Wagner, M.D., Ph.D.

  The Kennedy Krieger Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Neurology, Johns Hopkins University School of Medicine

Study Record Dates

• First Submitted: July 22, 2010
• First Posted: July 23, 2010
• Study Start: September 1, 2010
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: February 26, 2019
• Results First Posted: March 21, 2018

Record last verified: 2019-02

Locations

US (1)