Cystic Fibrosis and Endothelial Function: At Rest and During Exercise

Cystic Fibrosis Clinical Trial

Official title:

Influence of Cystic Fibrosis on Vascular Endothelial Function at Rest and During Exercise

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01772758
• Other study ID #: CFD Study
• Status: Completed
• Phase: Phase 2
• Start date: August 2011
• Est. completion date: June 21, 2016

Study information

• Verified date: June 2019
• Source: Augusta University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: June 21, 2016
• Est. primary completion date: June 21, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 7 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

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.)
• 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.)

Dietary Supplement:
• Antioxidant Cocktail
Vitamin C (1000 mg) , Vitamin E (600 IU) , and alpha-lipoic acid (600 mg). all BID

Locations

Country	Name	City	State
United States	Georgia Prevention Institute/ Laboratory of Integrative and Exercise Physiology	Augusta	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Augusta University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage Flow-Mediated Dilation (FMD)	Brachial artery FMD induced by reactive hyperemia assessed vascular endothelial function at baseline and several hours after treatment.	pre-treatment Baseline and 2-3 hours post-treatment

External Links

•   Laboratory of Integrative and Exercise Physiology Website