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

Primary Purpose

Cystic Fibrosis

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Sildenafil (Acute-1 hour)
Sildenafil (Subchronic-4 weeks)
Placebo
Sponsored by
Augusta University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cystic Fibrosis focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Augusta University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Acute Study: Sildenafil first, then Placebo

Acute Study: Placebo first, then Sildenafil

Sub-Chronic Study Sildenafil

Arm 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.

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
February 4, 2014
Last Updated
April 23, 2020
Sponsor
Augusta University
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT02057458
Brief Title
Blood Flow and Vascular Function in Cystic Fibrosis
Acronym
CF-FLOW
Official Title
Role of Blood Flow and Vascular Function on Exercise Capacity in Cystic Fibrosis
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
April 2014 (Actual)
Primary Completion Date
July 2018 (Actual)
Study Completion Date
July 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Augusta University
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Acute Study: Sildenafil first, then Placebo
Arm Type
Experimental
Arm 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.
Arm Title
Acute Study: Placebo first, then Sildenafil
Arm Type
Experimental
Arm 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.
Arm Title
Sub-Chronic Study Sildenafil
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Sildenafil (Acute-1 hour)
Other Intervention Name(s)
Viagra, Revatio
Intervention Description
Vascular function will be assessed 1 hour following oral ingestion of sildenafil (50 mg)
Intervention Type
Drug
Intervention Name(s)
Sildenafil (Subchronic-4 weeks)
Other Intervention Name(s)
Viagra, Revatio
Intervention Description
Vascular function will be assessed 4 weeks following 20 mg three times per day (TID) of sildenafil for four weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Sugar pill designed to mimic the sildenafil treatment
Primary Outcome Measure Information:
Title
Acute Study: Percentage Flow-Mediated Dilation (FMD)
Description
FMD determined one hour after ingestion of 50 mg Sildenafil or placebo
Time Frame
pre-treatment Baseline and 1 hour post-treatment
Title
Baseline Diameter
Description
Brachial Artery Diameter during FMD (pre-occlusion or "baseline")
Time Frame
pre-treatment Baseline and following 4 weeks sub-chronic treatment
Title
Peak Diameter
Description
Peak Brachial Artery Diameter during FMD (post-occlusion)
Time Frame
pre-treatment Baseline and following 4 weeks sub-chronic treatment
Title
Absolute Change in Diameter
Description
Absolute change in brachial artery diameter taken from the FMD assessment
Time Frame
pre-treatment Baseline and following 4 weeks sub-chronic treatment
Title
FEV1 (% Predicted)
Description
Forced Expiratory Volume in the first second expressed as a percent predicted.
Time Frame
pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment
Title
VO2 Peak (Absolute)
Description
absolute (L/min) peak oxygen consumption during maximal exercise test
Time Frame
pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment
Title
VO2 Peak (Relative)
Description
relative (mL/kg/min) peak oxygen consumption during maximal exercise test
Time Frame
pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment
Title
VO2 Peak (Percent Predicted)
Description
Maximal Oxygen consumption expressed as percent predicted taken from maximal exercise test.
Time Frame
pre-treatment Baseline and 1 hour post-treatment, and 4 weeks sub-chronic treatment
Title
VE Peak
Description
peak ventilation (L/min) during maximal exercise test
Time Frame
pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment
Title
RER Peak
Description
peak respiratory exchange ratio during maximal exercise test
Time Frame
pre-treatment Baseline, 1 hour post-treatment, and following 4 weeks sub-chronic treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ryan Harris, Ph.D.
Organizational Affiliation
Augusta University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Augusta University
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
Citations:
PubMed Identifier
33105385
Citation
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.
Results Reference
derived
Links:
URL
http://www.livep.net
Description
Laboratory of Integrative Vascular and Exercise Physiology

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Blood Flow and Vascular Function in Cystic Fibrosis

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