Blood Flow and Vascular Function in Cystic Fibrosis

NCT02057458 | Completed Phase 2 Results DMC

• 2 other identifiers: DK100783R21DK100783
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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.

Conditions

Cystic Fibrosis

Keywords

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

Outcome Measures

Primary Outcomes (10)

• 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

• Baseline Diameter

  Brachial Artery Diameter during FMD (pre-occlusion or "baseline")

  pre-treatment Baseline and following 4 weeks sub-chronic treatment

• Peak Diameter

  Peak Brachial Artery Diameter during FMD (post-occlusion)

  pre-treatment Baseline and following 4 weeks sub-chronic treatment

• 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

• 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

• 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

• 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

• 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

• VE Peak

  peak ventilation (L/min) during maximal exercise test

  pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment

• RER Peak

  peak respiratory exchange ratio during maximal exercise test

  pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment

Study Arms (3)

Acute Study: Sildenafil first, then Placebo

EXPERIMENTAL

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); Drug: Placebo

Acute Study: Placebo first, then Sildenafil

EXPERIMENTAL

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); Drug: Placebo

Sub-Chronic Study Sildenafil

EXPERIMENTAL

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)

Interventions

Sildenafil (Acute-1 hour) DRUG

Vascular function will be assessed 1 hour following oral ingestion of sildenafil (50 mg)

Also known as: Viagra, Revatio

Acute Study: Placebo first, then Sildenafil; Acute Study: Sildenafil first, then Placebo

Sildenafil (Subchronic-4 weeks) DRUG

Vascular function will be assessed 4 weeks following 20 mg three times per day (TID) of sildenafil for four weeks

Also known as: Viagra, Revatio

Sub-Chronic Study Sildenafil

Placebo DRUG

Sugar pill designed to mimic the sildenafil treatment

Acute Study: Placebo first, then Sildenafil; Acute Study: Sildenafil first, then Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Augusta University: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Augusta University

Augusta, Georgia, 30912, United States

Location

Related Publications (1)

• Rodriguez-Miguelez P, Seigler N, Ishii H, Crandall R, McKie KT, Forseen C, Harris RA. Exercise Intolerance in Cystic Fibrosis: Importance of Skeletal Muscle. Med Sci Sports Exerc. 2021 Apr 1;53(4):684-693. doi: 10.1249/MSS.0000000000002521.

  PMID: 33105385 DERIVED

Related Links

• Laboratory of Integrative Vascular and Exercise Physiology

MeSH Terms

Conditions

Cystic Fibrosis; Inflammation; Lung Diseases

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Ryan Harris, PhD
• Organization: Augusta University

ryharris@augusta.edu

7067215998

Study Officials

• Ryan Harris, Ph.D.

  Augusta University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: February 4, 2014
• First Posted: February 7, 2014
• Study Start: April 1, 2014
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2018
• Last Updated: April 24, 2020
• Results First Posted: April 24, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will share

Locations

US (1)