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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Ryan Harris, Augusta University

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.

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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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis

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




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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02057458


Locations
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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
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Principal Investigator: Ryan Harris, Ph.D. Augusta University
  Study Documents (Full-Text)

Documents provided by Ryan Harris, Augusta University:
Additional Information:
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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    Key Record Dates
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:
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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