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Tadalafil and Sildenafil for Duchenne Muscular Dystrophy

This study has been completed.
Sponsor:
Collaborator:
Parent Project Muscular Dystrophy
Information provided by (Responsible Party):
Ron Victor, Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier:
NCT01359670
First received: May 23, 2011
Last updated: August 19, 2013
Last verified: August 2013
  Purpose

This study, supported by Parent Project Muscular Dystrophy, will determine if tadalafil or sildenafil can improve muscle blood flow during exercise in boys with Duchenne muscular dystrophy.


Condition Intervention
Duchenne Muscular Dystrophy
Drug: Tadalafil
Drug: Sildenafil

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Functional Muscle Ischemia and PDE5A Inhibition in Duchenne Muscular Dystrophy

Resource links provided by NLM:


Further study details as provided by Cedars-Sinai Medical Center:

Primary Outcome Measures:
  • Functional muscle ischemia [ Time Frame: For 5 study visits ] [ Designated as safety issue: No ]
    Measured by the decrease in muscle tissue oxygenation (near infrared spectroscopy) and blood flow (Doppler ultrasound) evoked by reflex sympathetic activation in exercising forearm muscle.


Secondary Outcome Measures:
  • Cardiac Function [ Time Frame: For 5 study visits ] [ Designated as safety issue: No ]
    Echocardiogram

  • EKG Monitoring [ Time Frame: 5 times over about 6 weeks ] [ Designated as safety issue: Yes ]
    48 hour Holter monitoring

  • 6 Minute Walk Test [ Time Frame: For 5 study visits ] [ Designated as safety issue: No ]
  • Physical Activity [ Time Frame: 5 times over about 6-weeks ] [ Designated as safety issue: No ]
    Assessed by accelerometers

  • Quality of Life [ Time Frame: For 5 study visits ] [ Designated as safety issue: No ]
    PedsQL inventory


Enrollment: 30
Study Start Date: May 2011
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tadalafil Drug: Tadalafil
Escalating dose (0.25 mg/kg, 0.5 mg/kg, 1.0 mg/kg; once daily) over 2 weeks
Other Names:
  • Cialis
  • Adcirca
Experimental: Sildenafil Drug: Sildenafil
Escalating dose (0.25 mg/kg, 0.5 mg/kg, 1.0 mg/kg; four times daily) over 2 weeks
Other Names:
  • Viagra
  • Revatio

Detailed Description:

Duchenne muscular dystrophy (DMD) is a rare, progressive and fatal muscle disease affecting boys and accounts for 80% of muscular dystrophy cases. Tadalafil and sildenafil are medications approved by the FDA for the treatment of erectile dysfunction and pulmonary hypertension. This class of medication improves muscle blood flow in a mouse model of muscular dystrophy, but their benefit to boys with DMD is unknown. The purpose of this study is to 1) determine if tadalafil or sildenafil can improve muscle blood flow during exercise in boys with DMD; and 2) to inform the design of a subsequent, randomized, multi-center trial with clinical endpoints.

The investigators will enroll boys with DMD between the ages of 7 and 15 years who are ambulatory and without clinical heart failure. Participants will undergo 6 visits over the course of 5 weeks. The initial visit will include a medical history, physical exam, echocardiogram, and blood draw to determine eligibility for the study. Boys will be given a Holter monitor (a heart monitor) to wear for 48 hours to observe any irregular heartbeats or abnormalities.

Eligible boys will be randomized to one of the two study drugs: tadalafil or sildenafil. The boys will take a low dose (0.25mg/kg) of the study drug for the first 2 days and an intermediate dose (0.5mg/kg) for the subsequent 5 days. Then, boys will take a higher dose (1.0mg/kg) of the study drug for 1 week. Tadalafil will be taken once daily and sildenafil will be taken four times daily.

Study visits will occur 2 times at baseline, 2 times during the medication, and 1 time after washout of the medication. For these visits, boys will undergo an arm blood flow and hand grip exercise protocol. In this procedure, blood flow and oxygen delivery to the forearm muscles will be measured (noninvasively) before and during application of lower body negative pressure at rest and during handgrip exercise. Lower body negative pressure stimulates the blood flow changes that normally occur when a person sits up after lying down. During these visits, boys will complete a quality of life questionnaire, echocardiogram, and 6-minute walk tests. At home, boys will wear an accelerometer to measure physical activity and a Holter monitor to check for irregular heartbeats.

For boys who wish to continue with the study, there will be an option to cross-over and complete study visits with the drug they did not originally receive.

  Eligibility

Ages Eligible for Study:   7 Years to 15 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of DMD confirmed by muscle biopsy or DNA analysis
  2. Age 7-15y
  3. Ambulatory
  4. No clinical evidence of heart failure

Exclusion Criteria:

  1. Hypertension, diabetes, or heart failure by standard clinical criteria
  2. Elevated BNP level (>100 pg/ml)
  3. LVEF < 50%
  4. Wheelchair bound
  5. Cardiac rhythm disorder, specifically: rhythm other than sinus, SVT, atrial fibrillation, ventricular tachycardia
  6. Continuous ventilatory support
  7. Liver disease
  8. Renal impairment
  9. Contraindications to tadalafil or sildenafil (use of nitrates, alpha-blockers, CYP3A inhibitors, amlodipine, or other PDE5A inhibitors)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01359670

Locations
United States, California
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
Sponsors and Collaborators
Cedars-Sinai Medical Center
Parent Project Muscular Dystrophy
Investigators
Principal Investigator: Ronald Victor, MD Cedars-Sinai Medical Center
  More Information

No publications provided

Responsible Party: Ron Victor, Associate Director of the Heart Institute, Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier: NCT01359670     History of Changes
Other Study ID Numbers: PPMD
Study First Received: May 23, 2011
Last Updated: August 19, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Cedars-Sinai Medical Center:
Duchenne
muscular dystrophy
tadalafil
sildenafil
muscle ischemia
exercise

Additional relevant MeSH terms:
Muscular Dystrophy, Duchenne
Tadalafil
Muscular Dystrophies
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Sildenafil
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents

ClinicalTrials.gov processed this record on September 18, 2014