Blood Flow and Vascular Function in Cystic Fibrosis

Cystic Fibrosis Clinical Trial

— CF-FLOW  

Official title:

Role of Blood Flow and Vascular Function on Exercise Capacity in Cystic Fibrosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02057458
• Other study ID #: DK100783
• Secondary ID: R21DK100783
• Status: Completed
• Phase: Phase 2
• Start date: April 2014
• Est. completion date: July 2018

Study information

• Verified date: April 2020
• Source: Augusta University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: July 2018
• Est. primary completion date: July 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• Sildenafil (Acute-1 hour)
Vascular function will be assessed 1 hour following oral ingestion of sildenafil (50 mg)
• Sildenafil (Subchronic-4 weeks)
Vascular function will be assessed 4 weeks following 20 mg three times per day (TID) of sildenafil for four weeks
• Placebo
Sugar pill designed to mimic the sildenafil treatment

Locations

Country	Name	City	State
United States	Augusta University	Augusta	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Augusta University	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

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

External Links

•   Laboratory of Integrative Vascular and Exercise Physiology