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Cystic Fibrosis and Endothelial Function: At Rest and During Exercise

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ClinicalTrials.gov Identifier: NCT01772758
Recruitment Status : Completed
First Posted : January 21, 2013
Results First Posted : January 10, 2018
Last Update Posted : January 10, 2018
Sponsor:
Information provided by (Responsible Party):
Ryan Harris, Augusta University

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.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: BH4 5mg Drug: BH4 20mg Dietary Supplement: Antioxidant Cocktail Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 64 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Other
Official Title: Influence of Cystic Fibrosis on Vascular Endothelial Function at Rest and During Exercise
Study Start Date : August 2011
Actual Primary Completion Date : June 21, 2016
Actual Study Completion Date : June 21, 2016


Arm Intervention/treatment
Experimental: Protocol 1: AOC
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.
Dietary Supplement: Antioxidant Cocktail
Vitamin C (1000 mg) , Vitamin E (600 IU) , and alpha-lipoic acid (600 mg). all BID

Experimental: Protocol 2: BH4 (5mg)
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.
Drug: BH4 5mg
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.)
Other Names:
  • Tetrahydrobiopterin
  • Kuvan

Experimental: Protocol 2: BH4 (20mg)
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.
Drug: BH4 20mg
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.)
Other Names:
  • Tetrahydrobiopterin
  • Kuvan

No Intervention: Healthy Controls
baseline measurements were done with no intervention



Primary Outcome Measures :
  1. Percentage Flow-Mediated Dilation (FMD) [ Time Frame: pre-treatment Baseline and 2-3 hours post-treatment ]
    Brachial artery FMD induced by reactive hyperemia assessed vascular endothelial function at baseline and several hours after treatment.



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Ages Eligible for Study:   7 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
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)

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): NCT01772758


Locations
United States, Georgia
Georgia Prevention Institute/ Laboratory of Integrative and Exercise Physiology
Augusta, Georgia, United States, 30912
Sponsors and Collaborators
Augusta University
Investigators
Principal Investigator: Ryan Harris, PhD, CES Augusta University

Additional Information:
Responsible Party: Ryan Harris, Principal Investigator, Augusta University
ClinicalTrials.gov Identifier: NCT01772758     History of Changes
Other Study ID Numbers: CFD Study
First Posted: January 21, 2013    Key Record Dates
Results First Posted: January 10, 2018
Last Update Posted: January 10, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Keywords provided by Ryan Harris, Augusta University:
CF, cystic fibrosis, exercise

Additional relevant MeSH terms:
Fibrosis
Cystic Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Antioxidants
Verapamil
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Calcium Channel Blockers
Membrane Transport Modulators
Vasodilator Agents