Viagra Trial in Children and Young Adults With CF

Sildenafil Trial in Children and Young Adults With CF

This study is not yet open for participant recruitment.

Verified by Children's Hospital Medical Center, Cincinnati, September 2010

First Received: September 1, 2010   No Changes Posted

Sponsor:	Children's Hospital Medical Center, Cincinnati
Information provided by:	Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier:	NCT01194232

  Purpose

Cystic Fibrosis (CF), the most common inherited disease in Caucasians, is characterized by chronic pulmonary inflammation and progressive loss of gas exchange units that eventually results in respiratory failure. There is strong evidence that, in CF, abnormally low perfusion carries a high risk of death independent from the presence of pulmonary hypertension. However, the evolution of pulmonary vascular disease in CF and how it might contribute to the rate of decline in lung function is not known. Our knowledge remains limited to the results of old observational studies which concluded that the major causes of pulmonary vascular remodeling and hypertension in CF are hypoxic respiratory failure and destruction of lung tissue. Our recent data obtained by state-of-the-art Magnetic Resonance Imaging (MRI) of the pulmonary circulation, challenges the existing paradigm. We demonstrate that in the absence of hypoxia, significant changes in pulmonary perfusion and in surrogate measures of vascular resistance as well as in collateral blood flow begin early in the course of CF. Newly developed therapeutics have altered dramatically the course of patients suffering from pulmonary vascular disease. Through this 8 week trial, we will examine by Magnetic Resonance Imaging the effect of Sildenafil on pulmonary perfusion and systemic vascularization of the lungs in subjects with mild to moderate disease.

Condition	Intervention	Phase
Cystic Fibrosis With Mild to Moderate Lung Disease CMRI of Lung Perfusion Lung Perfusion Lung Vascularization	Drug: Sildenafil	Phase I Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Control: Uncontrolled Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Randomized Controlled Study of Sildenafil in Children and Young Adults With Mild to Moderate Cystic Fibrosis Lung Disease

Resource links provided by NLM:

Genetics Home Reference related topics: cystic fibrosis

MedlinePlus related topics: Cystic Fibrosis

Drug Information available for: Sildenafil Sildenafil citrate

U.S. FDA Resources

Further study details as provided by Children's Hospital Medical Center, Cincinnati:

Primary Outcome Measures:

• Increase pulmonary perfusion [ Time Frame: 8 week visit ] [ Designated as safety issue: No ]
  • Increase of pulmonary perfusion by a minimum of 15% as measured by gadolinium contrast MRI with segmental perfusion and scored on a continuous scale;
  
  

Secondary Outcome Measures:

• Improved lung function [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Improved exercise performance as measured by the following variables:

  • Ventilatory equivalent of O2 and CO2 (VEO2 and VECO2)
  • Maximum oxygen consumption (VO2 max)
  
  

Estimated Enrollment:	36
Study Start Date:	October 2010
Estimated Study Completion Date:	September 2012
Estimated Primary Completion Date:	March 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Sildenafil: Experimental 24 subjects will receeive 8 week course of Sildenafil administered at a dose of 1 mg / Kg three times a day with a maximum dose of 20 mg per dose.	Drug: Sildenafil 8 week course of Sildenafil administered at a dose of 1 mg / Kg three times a day with a maximum dose of 20 mg per dose.

  Eligibility

Ages Eligible for Study:	8 Years to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

• Age 8 years to age 21 years
• Diagnosis of cystic fibrosis confirmed by a prior sweat chloride evaluation of > 60 mmol/liter or by two identified CFTR mutations on genetic analysis
• Able to perform acceptable and repeatable spirometry per American Thoracic Society/European Respiratory Society (ATS/ERS) joint consensus criteria.
• Have valid spirometry data for at least 3 years
• Must have mild to moderate lung disease (Mild lung disease will be defined as an FEV1%p of 80-99% predicted. Moderate lung disease will be defined as an FEV1%p of 60-79% predicted.)
• If under the age of 18, the subject must assent to participation in the study, and the subject's parent or guardian must be able to give written informed consent and comply with the requirements of the study protocol
• If 18 years of age or older, the subject must be able to give written parental permission and comply with the requirements of the study protocol
• For female subjects: negative serum pregnancy test and must be willing to use contraception during study participation
• Able to tolerate MRI without sedation
• Subjects who are on alternating monthly on/off cycles of inhaled antibiotics must be willing to be off of inhaled antibiotic therapy for one "on" cycle.
• Must be currently enrolled in CCHMC IRB#: 2008-0926 5.2 Exclusion Criteria

Research subjects will be excluded from the study based on:

• History of CF-related liver disease with portal hypertension
• Currently smoking cigarettes or other tobacco products
• Use of daytime oxygen supplementation
• Previous organ transplantation
• Unstable or uncontrolled hypertension
• Ongoing use of oral corticosteroids
• For female subjects: pregnancy or lactation and unwillingness to use contraception during study participation
• Any hemodynamically significant congenital or acquired cardiac disease or significant cardiomyopathy, hematologic disease (i.e. hemoglobinopathies), or pulmonary disease associated with an increased risk of pulmonary perfusion defects or pulmonary hypertension other than as an outcome of CF
• History of renal and/or hepatic insufficiency, defined as cystatin-C level that exceeds normal range and a previous diagnosis of liver cirrhosis.
• History of uncontrolled asthma defined as oral steroid dependent
• History of hypersensitivity to gadolinium (Magnevist)
• Contraindications specific to MRI including a history of claustrophobia, cardiac pacemaker, or other non-MRI compatible surgical implants (This includes neuro-stimulators containing electrical circuitry, or which generate electrical signals and/or have moving metal parts, and metal orthopedic pins or plates. The research coordinator and/or the MRI technologist will screen all subjects using the standard checklist of medical history and safety questions used by the Radiology Department in routine clinical scans.)
• Daily use of montelukast and ibuprofen
• Use of nitrate medicines or other drugs known to have unsafe interactions with Sildenafil
• Known allergy to Sildenafil
• Inability to comply with study procedures

Laboratory Exclusion Criteria for research subjects (based on history or bloodwork before first MRI):

• Positive sputum, epiglottic, or brochoalveolar lavage culture for Mycobacterium abscessus during the 2 years prior to enrollment
• A positive serum pregnancy test
• Serum creatinine > two times the upper limit of normal for age
• A serum Cystatin C outside of normal range for age

  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01194232

Contacts

Contact: Lorrie Duan, RN	513-636-7089	lorrie.duan@cchmc.org
Contact: Margo Moore, RN	60394	margo.moore@cchmc.org

Locations

United States, Ohio

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229