PDE Inhibitors in DMD Study (Acute Dosing Study)

NCT01580501 | Completed Phase 1

• 1 other identifier: PRO 27521
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

PDE5A inhibition, which boosts NO-cGMP signaling, will relieve functional muscle ischemia and restore normal blood flow regulation (i.e., functional sympatholysis) during exercise in boys with DMD. The investigators specific aim is to perform an efficient dose-titration study to inform the design of a randomized multicenter trial of PDE5A inhibition for clinical skeletal muscle and cardiac endpoints.

Conditions

Duchenne Muscular Dystrophy

Outcome Measures

Primary Outcomes (1)

• Pre vs. post treatment change in functional sympatholysis by NIR for each dose of each drug.

  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 Outcomes (1)

• Sympatholysis measured by brachial artery Doppler ultrasound

Interventions

Tadalafil and Sildenafil DRUG

PDE-5 Inhibitor; Low dosages will be 0.5mg/kg and high dosages will be 1.0mg/kg

Also known as: Tadalafil/Cialis, Sildenafil/Viagra

Eligibility Criteria

• Age: 7 Years - 15 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• diagnosis of DMD confirmed by muscle biopsy or DNA analysis
• age 7-15y
• ambulatory
• no clinical evidence of heart failure

You may not qualify if:

• hypertension, diabetes, or heart failure by standard clinical criteria
• elevated BNP level (\>100 pg/ml)
• LVEF \< 50%
• non-ambulatory
• cardiac rhythm disorder, specifically: rhythm other than sinus, SVT, atrial fibrillation, ventricular tachycardia
• continuous ventilatory support
• liver disease
• renal impairment
• contraindications to sildenafil (use of nitrates, alpha-blockers, CYP3A inhibitors, amlodipine, or other PDE5A inhibitors)

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead

Study Sites (1)

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Interventions

Tadalafil; Sildenafil Citrate

Condition Hierarchy (Ancestors)

Muscular Dystrophies; 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)

Carbolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Purines

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Director of the Hypertension Center

Study Record Dates

• First Submitted: April 17, 2012
• First Posted: April 19, 2012
• Study Start: March 1, 2012
• Primary Completion: March 1, 2013
• Last Updated: January 28, 2014

Record last verified: 2014-01

Locations

US (1)