Cystic Fibrosis and Endothelial Function: At Rest and During Exercise

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

64 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-08-31

Study Completion Date

2016-06-21

Brief Summary

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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.

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Detailed Description

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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.

Conditions

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Cystic Fibrosis

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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.

Group Type EXPERIMENTAL

Antioxidant Cocktail

Intervention Type DIETARY_SUPPLEMENT

Vitamin C (1000 mg) , Vitamin E (600 IU) , and alpha-lipoic acid (600 mg). all BID

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.

Group Type EXPERIMENTAL

BH4 5mg

Intervention Type DRUG

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.)

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.

Group Type EXPERIMENTAL

BH4 20mg

Intervention Type DRUG

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.)

Healthy Controls

baseline measurements were done with no intervention

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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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.)

Intervention Type 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.)

Intervention Type DRUG

Antioxidant Cocktail

Vitamin C (1000 mg) , Vitamin E (600 IU) , and alpha-lipoic acid (600 mg). all BID

Intervention Type DIETARY_SUPPLEMENT

Other Intervention Names

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Tetrahydrobiopterin Kuvan Tetrahydrobiopterin Kuvan

Eligibility Criteria

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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)

Minimum Eligible Age

7 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes