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

Primary Purpose

Cystic Fibrosis

Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Acute Antioxidant
Chronic Antioxidant
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 Endothelial Function, Maximal Exercise Capacity, Flow Mediated Dilation, Antioxidant, FEV1

Eligibility Criteria

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

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

Sites / Locations

  • Georgia Prevention Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Acute Antioxidant Treatment

Chronic Antioxidant Treatment

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Acute Change in Flow mediated dilation
Flow-Mediated Dilation will be determined at baseline and 2 hours following acute antioxidant treatment
Chronic Change in Flow mediated dilation
Flow-Mediated Dilation will be determined at baseline, week 4, week 8 and week 12.
Acute Change in exercise capacity (VO2 peak)
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
Chronic Change in exercise capacity (VO2 peak)
Subjects will perform a maximal exercise capacity test at baseline, week 4, week 8, and week 12.

Secondary Outcome Measures

Full Information

First Posted
February 19, 2016
Last Updated
July 18, 2022
Sponsor
Augusta University
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1. Study Identification

Unique Protocol Identification Number
NCT02690064
Brief Title
Mechanisms for Vascular Dysfunction and Exercise Tolerance in CF
Acronym
CF-AOX
Official Title
Mechanisms for Vascular Dysfunction and Exercise Tolerance in CF
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 2015 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
January 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Augusta University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
Keywords
Endothelial Function, Maximal Exercise Capacity, Flow Mediated Dilation, Antioxidant, FEV1

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Acute Antioxidant Treatment
Arm Type
Experimental
Arm Description
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.
Arm Title
Chronic Antioxidant Treatment
Arm Type
Experimental
Arm Description
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
Acute Antioxidant
Other Intervention Name(s)
Vitamin C, Vitamin E, Alpha Lipoic Acid, Resveratrol, Mitoquinol (MitoQ)
Intervention Description
Flow-Mediated Dilation will be determined at baseline and 2 hours following acute antioxidant treatment
Intervention Type
Dietary Supplement
Intervention Name(s)
Chronic Antioxidant
Other Intervention Name(s)
Vitamin C, Vitamin E, Alpha Lipoic Acid, Resveratrol, Mitoquinol (MitoQ)
Intervention Description
Flow-Mediated Dilation will be determined at baseline, week 4, week 8, and week 12.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Flow-Mediated Dilation will be determined at baseline and 2 hours following acute antioxidant treatment
Primary Outcome Measure Information:
Title
Acute Change in Flow mediated dilation
Description
Flow-Mediated Dilation will be determined at baseline and 2 hours following acute antioxidant treatment
Time Frame
Change from baseline (2 hours)
Title
Chronic Change in Flow mediated dilation
Description
Flow-Mediated Dilation will be determined at baseline, week 4, week 8 and week 12.
Time Frame
Baseline, week 4, week 8, and week 12
Title
Acute Change in exercise capacity (VO2 peak)
Description
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
Time Frame
Baseline and 2 hours following acute antioxidant treatment
Title
Chronic Change in exercise capacity (VO2 peak)
Description
Subjects will perform a maximal exercise capacity test at baseline, week 4, week 8, and week 12.
Time Frame
Baseline, week 4, week 8, and week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
7 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
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
Georgia Prevention Institute
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes

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Mechanisms for Vascular Dysfunction and Exercise Tolerance in CF

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