Back to resultsCystic Fibrosis and Endothelial Function: At Rest and During Exercise
Primary Purpose
Cystic Fibrosis
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
BH4 5mg
BH4 20mg
Antioxidant Cocktail
Sponsored by
About this trial
This is an interventional other trial for Cystic Fibrosis focused on measuring CF, cystic fibrosis, exercise
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%
- Resting oxygen saturation (room air) >90%
- Patients with or without CFRD
- 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)
Exclusion Criteria:
- Children 6 yrs. old and younger
- FEV1 percent predicted < 30%
- Resting oxygen saturation (room air) < 90%
- Clinical diagnosis of heart disease
- Pulmonary artery hypertension
- Febrile illness within two weeks of visit
- Current smokers
- Currently pregnant or nursing
- Individuals on vaso-active medications (i.e. nitrates, beta blockers, ACE inhibitors, etc.)
- Inability to swallow pills
- Patients with B. Cepacia (only ~3% of our CF center patient population)
Sites / Locations
- Georgia Prevention Institute/ Laboratory of Integrative and Exercise Physiology
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
No Intervention
Arm Label
Protocol 1: AOC
Protocol 2: BH4 (5mg)
Protocol 2: BH4 (20mg)
Healthy Controls
Arm Description
measurements at baseline and 2 hours following the antioxidant cocktail that is comprised of over the counter vitamins (vitamin C 1000mg, vitamin E 600 IU, and alpha lipoic acid 600 mg) that will be given in two doses, 30 minutes apart.
measurements at baseline and 3 hours following the single dose of 5mg/kg Kuvan® or sapropterin dihydrochloride which is a synthetic preparation of the dihydrochloride salt of naturally occurring tetrahydrobiopterin (BH4).BH4 has been shown in past studies to increase NO bioavailability.
measurements at baseline and 3 hours following the single dose of 20mg/kg Kuvan® or sapropterin dihydrochloride which is a synthetic preparation of the dihydrochloride salt of naturally occurring tetrahydrobiopterin (BH4).BH4 has been shown in past studies to increase NO bioavailability.
baseline measurements were done with no intervention
Outcomes
Primary Outcome Measures
Percentage Flow-Mediated Dilation (FMD)
Brachial artery FMD induced by reactive hyperemia assessed vascular endothelial function at baseline and several hours after treatment.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01772758
Brief Title
Cystic Fibrosis and Endothelial Function: At Rest and During Exercise
Official Title
Influence of Cystic Fibrosis on Vascular Endothelial Function at Rest and During Exercise
Study Type
Interventional
2. Study Status
Record Verification Date
June 2019
Overall Recruitment Status
Completed
Study Start Date
August 2011 (undefined)
Primary Completion Date
June 21, 2016 (Actual)
Study Completion Date
June 21, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Augusta University
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Perhaps one of the most disturbing aspects of Cystic Fibrosis (CF) is the associated premature death. Oxidative stress has been observed in patients with CF and exercise intolerance has been shown to predict mortality in patients with CF, regardless of how healthy their lungs are. A critical barrier to improving the quality of life and longevity in patients with CF is our lack of knowledge regarding the different reasons why patients with CF cannot exercise to the level of their peers. We have collected preliminary data to support our central hypothesis that oxidative stress contributes to the impairment in blood vessel function at rest and during exercise which ultimately oxygen transport and delivery resulting in exercise intolerance. Exercise is therapeutic medicine for patients with CF and this investigation represents a major breakthrough in the approach to begin understanding the physiological mechanisms which contribute to exercise intolerance in these patients.
Detailed Description
The overall goals of this proposal are to provide mechanistic evidence that oxidative stress contributes to 1) endothelial dysfunction and 2) exercise intolerance in patients with CF. This study consists of two separate sub-studies, or protocols. Protocol 1: AOC tested the effect of an antioxidant cocktail (AOC) on endothelial function at rest and during exercise in CF patients. Protocol 2: BH4 tested the effect of tetrahydrobiopterin (BH4) on endothelial function at rest and during exercise in CF patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
Keywords
CF, cystic fibrosis, exercise
7. Study Design
Primary Purpose
Other
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Non-Randomized
Enrollment
64 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Protocol 1: AOC
Arm Type
Experimental
Arm Description
measurements at baseline and 2 hours following the antioxidant cocktail that is comprised of over the counter vitamins (vitamin C 1000mg, vitamin E 600 IU, and alpha lipoic acid 600 mg) that will be given in two doses, 30 minutes apart.
Arm Title
Protocol 2: BH4 (5mg)
Arm Type
Experimental
Arm Description
measurements at baseline and 3 hours following the single dose of 5mg/kg Kuvan® or sapropterin dihydrochloride which is a synthetic preparation of the dihydrochloride salt of naturally occurring tetrahydrobiopterin (BH4).BH4 has been shown in past studies to increase NO bioavailability.
Arm Title
Protocol 2: BH4 (20mg)
Arm Type
Experimental
Arm Description
measurements at baseline and 3 hours following the single dose of 20mg/kg Kuvan® or sapropterin dihydrochloride which is a synthetic preparation of the dihydrochloride salt of naturally occurring tetrahydrobiopterin (BH4).BH4 has been shown in past studies to increase NO bioavailability.
Arm Title
Healthy Controls
Arm Type
No Intervention
Arm Description
baseline measurements were done with no intervention
Intervention Type
Drug
Intervention Name(s)
BH4 5mg
Other Intervention Name(s)
Tetrahydrobiopterin, Kuvan
Intervention Description
Kuvan® or sapropterin dihydrochloride is a synthetic preparation of the dihydrochloride salt of naturally occurring tetrahydrobiopterin (BH4). Subjects received an oral dose of 5 mg/kg of Kuvan® (Biomarin Pharmaceuticals Inc.)
Intervention Type
Drug
Intervention Name(s)
BH4 20mg
Other Intervention Name(s)
Tetrahydrobiopterin, Kuvan
Intervention Description
Kuvan® or sapropterin dihydrochloride is a synthetic preparation of the dihydrochloride salt of naturally occurring tetrahydrobiopterin (BH4). Subjects received an oral dose of 20 mg/kg of Kuvan® (Biomarin Pharmaceuticals Inc.)
Intervention Type
Dietary Supplement
Intervention Name(s)
Antioxidant Cocktail
Intervention Description
Vitamin C (1000 mg) , Vitamin E (600 IU) , and alpha-lipoic acid (600 mg). all BID
Primary Outcome Measure Information:
Title
Percentage Flow-Mediated Dilation (FMD)
Description
Brachial artery FMD induced by reactive hyperemia assessed vascular endothelial function at baseline and several hours after treatment.
Time Frame
pre-treatment Baseline and 2-3 hours post-treatment
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%
Resting oxygen saturation (room air) >90%
Patients with or without CFRD
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)
Exclusion Criteria:
Children 6 yrs. old and younger
FEV1 percent predicted < 30%
Resting oxygen saturation (room air) < 90%
Clinical diagnosis of heart disease
Pulmonary artery hypertension
Febrile illness within two weeks of visit
Current smokers
Currently pregnant or nursing
Individuals on vaso-active medications (i.e. nitrates, beta blockers, ACE inhibitors, etc.)
Inability to swallow pills
Patients with B. Cepacia (only ~3% of our CF center patient population)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ryan Harris, PhD, CES
Organizational Affiliation
Augusta University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Georgia Prevention Institute/ Laboratory of Integrative and Exercise Physiology
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
Links:
URL
http://facebook.com/harrislab
Description
Laboratory of Integrative and Exercise Physiology Website
Learn more about this trial
Cystic Fibrosis and Endothelial Function: At Rest and During Exercise
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