Cystic Fibrosis and Endothelial Function: At Rest and During Exercise

NCT01772758 | Completed Phase 2 Results

• 1 other identifier: CFD Study
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

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.

Conditions

Cystic Fibrosis

Keywords

CF, cystic fibrosis, exercise

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (4)

Protocol 1: AOC

EXPERIMENTAL

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

Protocol 2: BH4 (5mg)

EXPERIMENTAL

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

Protocol 2: BH4 (20mg)

EXPERIMENTAL

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

Healthy Controls

NO INTERVENTION

baseline measurements were done with no intervention

Interventions

BH4 5mg 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.)

Also known as: Tetrahydrobiopterin, Kuvan

Protocol 2: BH4 (5mg)

BH4 20mg 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.)

Also known as: Tetrahydrobiopterin, Kuvan

Protocol 2: BH4 (20mg)

Antioxidant Cocktail DIETARY_SUPPLEMENT

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

Protocol 1: AOC

Eligibility Criteria

• Age: 7 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Augusta University: lead

Study Sites (1)

Georgia Prevention Institute/ Laboratory of Integrative and Exercise Physiology

Augusta, Georgia, 30912, United States

Location

Related Links

• Laboratory of Integrative and Exercise Physiology Website

MeSH Terms

Conditions

Cystic Fibrosis; Motor Activity

Interventions

sapropterin

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Behavior

Results Point of Contact

• Title: Ryan Harris, Ph.D.
• Organization: Augusta University

ryharris@augusta.edu

706-721-5998

Study Officials

• Ryan Harris, PhD, CES

  Augusta University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 16, 2012
• First Posted: January 21, 2013
• Study Start: August 1, 2011
• Primary Completion: June 21, 2016
• Study Completion: June 21, 2016
• Last Updated: June 20, 2019
• Results First Posted: January 10, 2018

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will share

Locations

US (1)