We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Tadalafil and Sildenafil for Duchenne Muscular Dystrophy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01359670
Recruitment Status : Completed
First Posted : May 25, 2011
Last Update Posted : August 20, 2013
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
Brief Summary:
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 or disease Intervention/treatment
Duchenne Muscular Dystrophy Drug: Tadalafil Drug: Sildenafil

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.


Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Functional Muscle Ischemia and PDE5A Inhibition in Duchenne Muscular Dystrophy
Study Start Date : May 2011
Primary Completion Date : May 2013
Study Completion Date : May 2013


Arms and Interventions

Arm Intervention/treatment
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


Outcome Measures

Primary Outcome Measures :
  1. Functional muscle ischemia [ Time Frame: For 5 study visits ]
    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 :
  1. Cardiac Function [ Time Frame: For 5 study visits ]
    Echocardiogram

  2. EKG Monitoring [ Time Frame: 5 times over about 6 weeks ]
    48 hour Holter monitoring

  3. 6 Minute Walk Test [ Time Frame: For 5 study visits ]
  4. Physical Activity [ Time Frame: 5 times over about 6-weeks ]
    Assessed by accelerometers

  5. Quality of Life [ Time Frame: For 5 study visits ]
    PedsQL inventory


Eligibility Criteria

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   7 Years to 15 Years   (Child)
Sexes 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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

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
First Posted: May 25, 2011    Key Record Dates
Last Update Posted: August 20, 2013
Last Verified: August 2013

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

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