Blood Flow and Vascular Function in Cystic Fibrosis (CF-FLOW)

Augusta University

Status and phase: Completed; Phase 2

Conditions: Cystic Fibrosis

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

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02057458

R21DK100783 (U.S. NIH Grant/Contract)

DK100783

Details and patient eligibility

About

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.

Full 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.

Enrollment: 19 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria.

• Diagnosis of CF and healthy controls
• Men and women (greater than 18 yrs. old)
• Resting oxygen saturation (room air) greater than 90%
• Forced expiratory volume (FEV1) percent predicted greater than 30%
• Patients with or without CF related diabetes
• Traditional CF-treatment medications
• Ability to perform reliable/reproducible pulmonary function tests (PFT)
• Clinically stable for 2 weeks (no exacerbations or need for antibiotic treatment within 2 weeks of testing or major change in medical status)

Exclusion Criteria.

• Children less than 17 years old
• Body mass less than 20 kg
• A diagnosis of pulmonary arterial hypertension (PAH)
• FEV1 less than 30% of predicted
• Resting oxygen saturation (SpO2) less than 90%
• Self-reported to be a smoker
• Current use of any vaso-active medications
• History of migraine headaches
• Pregnant or nursing at the time of the investigation
• A clinical diagnosis of cardiovascular disease, hypertension, or CF related diabetes

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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19 participants in 3 patient groups

Acute Study: Sildenafil first, then Placebo

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Sildenafil (Acute-1 hour)

Acute Study: Placebo first, then Sildenafil

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Sildenafil (Acute-1 hour)

Sub-Chronic Study Sildenafil

Experimental group

Description:

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.

Treatment:

Drug: Sildenafil (Subchronic-4 weeks)