Cystic Fibrosis and Endothelial Function: At Rest and During Exercise
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis
Intervention: BH4 5mg; BH4 20mg; Antioxidant Cocktail
Intervention description: 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.); 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.); Vitamin C (1000 mg) , Vitamin E (600 IU) , and alpha-lipoic acid (600 mg). all BID
Intervention MeSH terms: Antioxidants
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 64.0
Sex: All
Minimum age: 7 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: CF, cystic fibrosis, exercise

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.
    

Eligibility 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)