Cystic Fibrosis and Endothelial Function: At Rest and During Exercise

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Georgia Regents University
Sponsor:
Information provided by (Responsible Party):
Ryan Harris, Georgia Regents University
ClinicalTrials.gov Identifier:
NCT01772758
First received: October 16, 2012
Last updated: April 14, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Cystic Fibrosis
Drug: BH4
Dietary Supplement: Antioxidant Cocktail
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Official Title: Influence of Cystic Fibrosis on Vascular Endothelial Function at Rest and During Exercise

Resource links provided by NLM:


Further study details as provided by Georgia Regents University:

Primary Outcome Measures:
  • Acute Change in Blood flow regulation during exercise [ Time Frame: change from Baseline (2-3hours) ] [ Designated as safety issue: No ]
    Brachial artery blood flow and velocities (both antegrade and retrograde) will be determined during baseline and 60% maximal work rate intensity.

  • Acute Change in Flow mediated dilation [ Time Frame: change from Baseline (2-3hours) ] [ Designated as safety issue: No ]
    Flow-Mediated Dilation will be determined at baseline and 2 and 3 hours following acute antioxidant and BH4 treatment, respectively

  • Acute Change in Arterial Stiffness [ Time Frame: change from Baseline (2-3hours) ] [ Designated as safety issue: No ]
    Pulse wave velocity will be determined at baseline and 2 and 3 hours following acute antioxidant and BH4 treatment, respectively


Secondary Outcome Measures:
  • Acute Change in Biomarkers of oxidative stress [ Time Frame: change from Baseline (2-3hours) ] [ Designated as safety issue: No ]
    Ascorbyl and alkoxyl free radicals 8-isoprostane lipid hydroperoxide will all be determined at baseline and 2 and 3 hours following acute antioxidant and BH4 treatment, respectively


Estimated Enrollment: 80
Study Start Date: August 2011
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Antioxidant Cocktail
measurements at baseline and 2 hours following the antioxidant cocktail
Dietary Supplement: Antioxidant Cocktail
none
Other Names:
  • Vitamin C
  • Vitamin E
  • Alpha Lipoic Acid
Experimental: BH4
measurements will be performed at baseline and 3 hour following BH4 (5 mg/kg body mass) dissolved in apple juice.
Drug: BH4
none
Other Names:
  • Tetrahydrobiopterin
  • Kuvan

  Eligibility

Ages Eligible for Study:   7 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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)
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01772758

Contacts
Contact: Nichole Seigler, BA 706-721-5998 maseigler@georgiahealth.edu
Contact: Ryan A Harris, PhD, CES 706-721-5998 ryharris@georgiahealth.edu

Locations
United States, Georgia
Georgia Prevention Center/ Laboratory of Integrative and Exercise Physiology Recruiting
Augusta, Georgia, United States, 30912
Contact: Nichole Seigler, BA    706-721-5998    maseigler@georgiahealth.edu   
Sub-Investigator: Katie McKie, MD         
Sub-Investigator: Nichole Seigler, BA         
Sub-Investigator: Dabney Eidson, RRT         
Sub-Investigator: Valera Hudson, MD         
Sponsors and Collaborators
Georgia Regents University
Investigators
Principal Investigator: Ryan Harris, PhD, CES Georgia Regents University
  More Information

Additional Information:
No publications provided

Responsible Party: Ryan Harris, Principal Investigator, Georgia Regents University
ClinicalTrials.gov Identifier: NCT01772758     History of Changes
Other Study ID Numbers: CFD Study
Study First Received: October 16, 2012
Last Updated: April 14, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Antioxidants
Cystic Fibrosis
Fibrosis
Digestive System Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Lung Diseases
Pancreatic Diseases
Pathologic Processes
Respiratory Tract Diseases
Vitamins
Growth Substances
Micronutrients
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents

ClinicalTrials.gov processed this record on October 21, 2014