Blood Flow and Vascular Function in Cystic Fibrosis

Phase 2

Completed

Conditions: Cystic Fibrosis

Interventions: Drug: Sildenafil (Acute-1 hour)
Drug: Sildenafil (Subchronic-4 weeks)
Drug: Placebo

Registration Number: NCT02057458

Lead Sponsor: Augusta University

Brief Summary: Cystic fibrosis (CF) has many health consequences. A reduction in the ability to perform exercise in patients with CF is related to greater death rates, steeper decline in lung function, and more frequent lung infections. However, the physiological mechanisms for this reduced exercise capacity are unknown. The investigators laboratory recently published the first evidence of systemic vascular dysfunction in patients with CF. Therefore, it is reasonable to suspect that the blood vessels are involved with exercise intolerance in CF. This study will look at how 1) blood flow and 2) artery function contribute to exercise capacity in CF.

Detailed Description: The most disturbing aspect of Cystic Fibrosis (CF) is the associated premature death. Low exercise capacity predicts death in patients with CF and is also associated with a steeper decline in lung function and more lung infections. A critical barrier to improving exercise tolerance in patients with CF is the investigators lack of knowledge regarding the different physiological mechanisms which contribute to their lower exercise capacity. We have compelling data to indicate that the blood vessels may contribute to the low exercise capacity in CF. The impact of this proof of concept investigation will test Phosphodiesterase Type 5 inhibitors (PDE5) inhibitors as a potential therapy in CF and will explore blood flow and endothelial function as potential mechanisms which contribute to exercise intolerance in CF. Improvements in exercise capacity will not only contribute to a better quality of live for patients with CF, it will also increase longevity in these patients.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 19

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Acute Study: Sildenafil first, then Placebo	Sildenafil (Acute-1 hour)	In randomized order, on two separate days, endothelial function and exercise capacity will be determined 1 hour following a single dose of sildenafil (50 mg) or placebo.
Acute Study: Sildenafil first, then Placebo	Placebo	In randomized order, on two separate days, endothelial function and exercise capacity will be determined 1 hour following a single dose of sildenafil (50 mg) or placebo.
Acute Study: Placebo first, then Sildenafil	Placebo	In randomized order, on two separate days, endothelial function and exercise capacity will be determined 1 hour following a single dose of sildenafil (50 mg) or placebo.
Acute Study: Placebo first, then Sildenafil	Sildenafil (Acute-1 hour)	In randomized order, on two separate days, endothelial function and exercise capacity will be determined 1 hour following a single dose of sildenafil (50 mg) or placebo.
Sub-Chronic Study Sildenafil	Sildenafil (Subchronic-4 weeks)	Following the acute study, patients will be instructed to take 20 mg of sildenafil, three times a day, for 4 weeks. Endothelial function will be determined within 48 hours following the last dose.

Primary Outcome Measures

Name	Time	Method
Acute Study: Percentage Flow-Mediated Dilation (FMD)	pre-treatment Baseline and 1 hour post-treatment	FMD determined one hour after ingestion of 50 mg Sildenafil or placebo
Baseline Diameter	pre-treatment Baseline and following 4 weeks sub-chronic treatment	Brachial Artery Diameter during FMD (pre-occlusion or "baseline")
Peak Diameter	pre-treatment Baseline and following 4 weeks sub-chronic treatment	Peak Brachial Artery Diameter during FMD (post-occlusion)
Absolute Change in Diameter	pre-treatment Baseline and following 4 weeks sub-chronic treatment	Absolute change in brachial artery diameter taken from the FMD assessment
FEV1 (% Predicted)	pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment	Forced Expiratory Volume in the first second expressed as a percent predicted.
VO2 Peak (Absolute)	pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment	absolute (L/min) peak oxygen consumption during maximal exercise test
VO2 Peak (Relative)	pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment	relative (mL/kg/min) peak oxygen consumption during maximal exercise test
VO2 Peak (Percent Predicted)	pre-treatment Baseline and 1 hour post-treatment, and 4 weeks sub-chronic treatment	Maximal Oxygen consumption expressed as percent predicted taken from maximal exercise test.
VE Peak	pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment	peak ventilation (L/min) during maximal exercise test
RER Peak	pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment	peak respiratory exchange ratio during maximal exercise test