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

• ClinicalTrials.gov Identifier: NCT02057458
• Recruitment Status: Completed
• First Posted: February 7, 2014
• Results First Posted: April 24, 2020
• Last Update Posted: April 24, 2020
• Sponsor: Augusta University
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): Ryan Harris, Augusta University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cystic Fibrosis	Drug: Sildenafil (Acute-1 hour); Drug: Sildenafil (Subchronic-4 weeks); Drug: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 19 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Role of Blood Flow and Vascular Function on Exercise Capacity in Cystic Fibrosis
• Actual Study Start Date: April 2014
• Actual Primary Completion Date: July 2018
• Actual Study Completion Date: July 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Acute Study: Sildenafil first, then 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.	Drug: Sildenafil (Acute-1 hour); Vascular function will be assessed 1 hour following oral ingestion of sildenafil (50 mg); Other Names: Viagra; Revatio; Drug: Placebo; Sugar pill designed to mimic the sildenafil treatment
Experimental: Acute Study: Placebo first, then Sildenafil; 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.	Drug: Sildenafil (Acute-1 hour); Vascular function will be assessed 1 hour following oral ingestion of sildenafil (50 mg); Other Names: Viagra; Revatio; Drug: Placebo; Sugar pill designed to mimic the sildenafil treatment
Experimental: Sub-Chronic Study Sildenafil; 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.	Drug: Sildenafil (Subchronic-4 weeks); Vascular function will be assessed 4 weeks following 20 mg three times per day (TID) of sildenafil for four weeks; Other Names: Viagra; Revatio

Outcome Measures

Primary Outcome Measures :

1. Acute Study: Percentage Flow-Mediated Dilation (FMD) [ Time Frame: pre-treatment Baseline and 1 hour post-treatment ]
   FMD determined one hour after ingestion of 50 mg Sildenafil or placebo
2. Baseline Diameter [ Time Frame: pre-treatment Baseline and following 4 weeks sub-chronic treatment ]
   Brachial Artery Diameter during FMD (pre-occlusion or "baseline")
3. Peak Diameter [ Time Frame: pre-treatment Baseline and following 4 weeks sub-chronic treatment ]
   Peak Brachial Artery Diameter during FMD (post-occlusion)
4. Absolute Change in Diameter [ Time Frame: pre-treatment Baseline and following 4 weeks sub-chronic treatment ]
   Absolute change in brachial artery diameter taken from the FMD assessment
5. FEV1 (% Predicted) [ Time Frame: 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.
6. VO2 Peak (Absolute) [ Time Frame: pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment ]
   absolute (L/min) peak oxygen consumption during maximal exercise test
7. VO2 Peak (Relative) [ Time Frame: 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
8. VO2 Peak (Percent Predicted) [ Time Frame: 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.
9. VE Peak [ Time Frame: pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment ]
   peak ventilation (L/min) during maximal exercise test
10. RER Peak [ Time Frame: pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment ]
    peak respiratory exchange ratio during maximal exercise test

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

United States, Georgia

Augusta University

Augusta, Georgia, United States, 30912

Sponsors and Collaborators

Augusta University

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Ryan Harris, Ph.D.; Augusta University

  Study Documents (Full-Text)

Documents provided by Ryan Harris, Augusta University:

Study Protocol and Statistical Analysis Plan  [PDF] January 27, 2014

More Information

Additional Information:

Laboratory of Integrative Vascular and Exercise Physiology 

• Responsible Party: Ryan Harris, Assistant Professor, Augusta University
• ClinicalTrials.gov Identifier: NCT02057458
• Other Study ID Numbers: DK100783; R21DK100783 ( U.S. NIH Grant/Contract )
• First Posted: February 7, 2014
• Results First Posted: April 24, 2020
• Last Update Posted: April 24, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Keywords provided by Ryan Harris, Augusta University:

arterial stiffness; flow-mediated dilation; endothelial function; pulse wave velocity; inflammation; oxidative stress; pulmonary function test; Cystic Fibrosis; Lung Disease; Nitric Oxide; Exercise Capacity; CF; Muscle Function; Sildenafil; Viagra; Revatio

Additional relevant MeSH terms:

Cystic Fibrosis; Fibrosis; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Sildenafil Citrate; Vasodilator Agents; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Urological Agents