Mechanisms for Vascular Dysfunction and Exercise Tolerance in CF (CF-AOX)

January 27, 2025 updated by: Ryan Harris, Augusta University
Cystic fibrosis 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 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 and if oxidative stress contributes to both artery dysfunction and exercise intolerance in CF.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Cystic Fibrosis (CF) is the most common fatal genetic disease in North America. The most disturbing aspect of CF is the associated premature death, most often due to respiratory complications. Clinical manifestations of CF include not only lung dysfunction, but many other systemic consequences as well. Systemic oxidative stress and exercise intolerance are established phenotypes in patients with CF. Additionally, for the first time the investigators have recently published the presence of systemic endothelial dysfunction in a cohort of young patients with CF who exhibited normal oxygen saturation and spirometric function.

Exercise intolerance, the limitation of the ability to perform exercise at the expected level, has been shown to predict mortality in patients with CF independent of lung function. Exercise capacity (VO2 peak), an objective measurement of exercise tolerance, drops approximately 5-8% per year in patients with CF. This excessive decay in exercise capacity not only leads to more pulmonary infections and deterioration of lung function, it represents a 5-8 fold decline compared to healthy sedentary adults. Preventing the excessive annual reduction in exercise capacity is essential to increasing the quality of life and longevity of patients with CF. However, a critical barrier to improving exercise capacity in CF is the investigators lack of knowledge regarding the different physiological mechanisms that contribute to exercise intolerance. It is important to emphasize that decreases in lung function (FEV1) do not always contribute to reductions in VO2 peak. Furthermore, less than 2% of patients who have an FEV1 greater than 50% predicted will have a significant drop in hemoglobin oxygen saturation (SpO2) during maximal exercise. These data suggest that mechanisms other than lung function induced hypoxemia may be contributing to exercise intolerance in patients with CF.

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Georgia
      • Augusta, Georgia, United States, 30912
        • Georgia Prevention Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

7 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Diagnosis of CF and healthy controls
  • Men and women (> 18 yrs. old)
  • Boys and girls (7-17 yrs. old)
  • FEV1 percent predicted > 30%
  • Patients with or without CF related diabetes
  • Resting oxygen saturation (room air) >90%
  • Traditional CF-treatment medications
  • Ability to perform reliable/reproducible PFTs
  • Clinically stable for 2 weeks (no exacerbations or need for antibiotic treatment within 2 weeks of testing or major change in medical status)
  • Pancreatic sufficient and pancreatic insufficient patients

Exclusion Criteria:

  • Children 6 yrs. old and younger
  • FEV1 percent predicted < 30%
  • Resting oxygen saturation (room air) < 90%
  • Clinical diagnosis of heart disease, PAH
  • Febrile illness within two weeks of visit
  • Currently smoking, pregnant, or nursing
  • Individuals on vaso-active medications (i.e. nitrates, beta blockers, ACE inhibitors, etc.)
  • Patients with B. cepacia (only ~3% of our CF center patient population)
  • Treatment for pulmonary exacerbation within 4 weeks of a study visit

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Acute Antioxidant Treatment
Following an overnight fast, blood samples, flow-mediated dilation, lung function, and exercise capacity (VO2 peak) (post only) will be performed at baseline and 2 hours following either a single dose oral 1) antioxidant cocktail (1000 mg Vitamin C, 600 IU vitamin E, 600 mg Alpha Lipoic Acid) 2) Resveratrol (1500 mg) 3) Mitoquinol (10 mg) or placebo on two days separated by at least 72 hours.
Other: Placebo
Flow-Mediated Dilation will be determined at baseline and 2 hours following acute antioxidant treatment
Dietary supplement: Acute Antioxidant
Flow-Mediated Dilation will be determined at baseline and 2 hours following acute antioxidant treatment
Other Names:
  • Vitamin E
  • Vitamin C
  • Alpha Lipoic Acid
  • Resveratrol
  • Mitoquinol (MitoQ)
Experimental: Chronic Antioxidant Treatment
Following the completion of Arm 1, blood samples, flow-mediated dilation, lung function, and exercise capacity (VO2 peak) will be performed, only in patients with CF, at baseline, 4 weeks, 8 weeks, and 12 weeks following one of the following: 1) an anti-oxidant cocktail (vitamin C 1000 mg, vitamin E 400 IU, and alpha lipoic acid 600 mg) taken once a day, 2) 1500 mg Resveratrol once a day or 3) 10 mg Mitoquinol once a day.
Dietary supplement: Chronic Antioxidant
Flow-Mediated Dilation will be determined at baseline, week 4, week 8, and week 12.
Other Names:
  • Vitamin E
  • Vitamin C
  • Alpha Lipoic Acid
  • Resveratrol
  • Mitoquinol (MitoQ)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acute Change in Flow mediated dilation
Time Frame: Change from baseline (2 hours)
Flow-Mediated Dilation will be determined at baseline and 2 hours following acute antioxidant treatment
Change from baseline (2 hours)
Chronic Change in Flow mediated dilation
Time Frame: Baseline, week 4, week 8, and week 12
Flow-Mediated Dilation will be determined at baseline, week 4, week 8 and week 12.
Baseline, week 4, week 8, and week 12
Acute Change in exercise capacity (VO2 peak)
Time Frame: Baseline and 2 hours following acute antioxidant treatment
Subjects will perform a baseline maximal exercise capacity test and on a separate visit perform a maximal exercise capacity test 2 hours following acute antioxidant treatment
Baseline and 2 hours following acute antioxidant treatment
Chronic Change in exercise capacity (VO2 peak)
Time Frame: Baseline, week 4, week 8, and week 12
Subjects will perform a maximal exercise capacity test at baseline, week 4, week 8, and week 12.
Baseline, week 4, week 8, and week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Augusta University

Investigators

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2015

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

January 1, 2027

Study Registration Dates

First Submitted

February 19, 2016

First Submitted That Met QC Criteria

February 19, 2016

First Posted (Estimated)

February 24, 2016

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 27, 2025

Last Verified

January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CF-AOX

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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