Effects of an Antioxidant-Enriched Multivitamin Supplement on Inflammation and Oxidative Stress in Cystic Fibrosis
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis; Inflammation
Intervention: AquADEKs-2; control multivitamin
Intervention description: AquADEKs-2 contains standard amounts of fat-soluble vitamins (A, D, E, K) that are contained in typical CF multivitamin supplements plus several antioxidants including beta-carotene, mixed tocopherols (different forms of vitamin E), coenzyme Q10 (CoQ10), mixed carotenoids (lutein, lycopene and zeaxanthin), and the minerals zinc and selenium.; The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.
Intervention MeSH terms: Antioxidants
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 73.0
Sex: All
Minimum age: 10 Years
Healthy volunteers: No
Keywords: Antioxidants; Vitamins; Inflammation; Oxidative stress

Summary:

      The purpose of this study will be to evaluate the effects of a modified formulation of
      AquADEKs (AquADEKs-2) on markers of inflammation, antioxidant levels and oxidative stress.

      Cystic Fibrosis (CF) is a disease that affects the organs in the body such as the lungs. Some
      of the damage to the lungs of CF patients may be caused by something called
      oxidant/antioxidant imbalance and oxidative stress.

      Oxidation in the body is kind of what happens to an apple when it turns brown after being
      cut. And, just as a squeeze of lemon juice stops the oxidation of an apple, antioxidants can
      stop the rusting (or damage) inside our bodies by unstable oxygen molecules called free
      radicals. Free radicals can help fight off bacteria and viruses but too many of them do
      damage instead. Our bodies need antioxidants to keep things in balance so we have the right
      amount of free radicals.

      Many CF patients also have trouble digesting food and absorbing nutrients like vitamins. Many
      of the vitamins we rely on are antioxidants, like vitamins A, D, E, K and beta-carotene. In
      some people with CF, even though they take multivitamins and pancreatic enzymes, they still
      have low amounts of antioxidants. The investigators are looking to see if taking more
      vitamins and antioxidants will help CF patients.

      AquADEKs-2 is an investigational new drug (a drug that has not received approval by the Food
      and Drug Administration [FDA]). This research study is being done with the AquADEKs-2
      compared to a control multivitamin. The study drug, AquADEKs-2 contains standard amounts of
      fat-soluble vitamins (A, D, E, K) that are contained in typical CF multivitamin supplements
      plus several antioxidants including beta-carotene, mixed tocopherols (different forms of
      vitamin E), coenzyme Q10 (CoQ10), mixed carotenoids (lutein, lycopene and zeaxanthin), and
      the minerals zinc and selenium. The control multivitamin contains standard amounts of
      vitamins A, B, D, E, and K without additional antioxidant supplementation.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female ≥10 years of age

          -  Documentation of a Cystic Fibrosis (CF) diagnosis as evidenced by 1 or more clinical
             features consistent with the CF phenotype and 1 or more of the following criteria:

               -  Sweat chloride equal to or greater than 60 milliequivalent (mEq/L) by
                  quantitative pilocarpine iontophoresis test (QPIT)

               -  2 well-characterized mutations in the cystic fibrosis transmembrane conductance
                  regulator (CFTR) gene

          -  Pancreatic insufficiency documented by having a spot fecal elastase-1 (FE-1) ≤ 100μg/g
             in a stool sample done either historically or at the screening visit

          -  Clinically stable with no significant changes in health status within 2 weeks prior to
             randomization

          -  Forced expiratory volume over one second (FEV1) ≥ 40 and ≤ 100% of predicted for age
             based on the Wang (males < 18 years,females < 16 years) or Hankinson (males ≥ 18
             years, females ≥ 16 years) standardized equations at the screening visit

          -  Weight ≥ 30 kg at the screening visit

          -  Able to perform repeatable, consistent efforts in pulmonary function testing

          -  Able to tolerate sputum induction with 3% hypertonic saline and to expectorate with
             induction

          -  Written informed consent (and assent when applicable) obtained from subject or
             subject's legal representative

          -  Ability to swallow softgel capsules

        Exclusion Criteria:

          -  Subjects being treated with ivacaftor (Kalydeco™)

          -  Liver enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), or
             gamma-glutamyl transferase (GGT) > 3 times the upper limits of normal at the screening
             visit

          -  Use of antibiotics (oral, iv, and/or inhaled) for acute respiratory symptoms within 2
             weeks prior to randomization

          -  Active treatment for allergic bronchopulmonary aspergillosis (ABPA)

          -  Current use of oral corticosteroids in doses exceeding the equivalent of 10 mg
             prednisone/day or 20 mg prednisone every other day

          -  Active treatment for nontuberculous mycobacterial (NTM) infection

          -  Initiation of any new chronic therapy (e.g., ibuprofen, Pulmozyme®, hypertonic
             saline,azithromycin,Tobramycin Inhalation solution (TOBI®), Cayston® within 8 weeks
             prior to randomization

          -  Unwilling to discontinue current oral vitamin and antioxidant supplementation
             (e.g.,AquADEKs®, another source of β-carotene, vitamin A, vitamin E or
             tocopherols,vitamins D or K, n-acetylcysteine, glutathione, CoQ10, other
             over-the-counter antioxidant) for the duration of the study

          -  Use of vitamins (other than control vitamin) or antioxidants within 4 weeks prior to
             randomization

          -  Daily use of > 2 cans of Boost or Pulmocare dietary supplement formulas

          -  Known hypersensitivity to oral AquADEKs®

          -  For women of child bearing potential:

               1. positive pregnancy test at Visit 1 or at Visit 2, or

               2. lactating or

               3. unwilling to practice a medically acceptable form of contraception (acceptable
                  forms of contraception: abstinence, hormonal birth control, intrauterine device,
                  or barrier method plus a spermicidal agent)

          -  Subject unlikely to complete the study as determined by the Investigator

          -  Any condition that the Investigator believes would interfere with the intent of this
             study or would make participation not in the best interest of the subject

          -  Use of investigational therapies within 4 weeks prior to randomization

          -  Current tobacco smoker

          -  Current use of anticoagulant medications

          -  Severe malnutrition based either on having a BMI less than the 5th percentile for
             subjects < 18 years of age or a body mass index (BMI) less than 18 kg/m2 for subjects
             > 18 years of age.

          -  Subjects with poorly controlled CF-related diabetes on active insulin therapy, defined
             as having a Glycosylated Hemoglobin (HgbA1c) ≥ 7.5% at the most recent historic
             evaluation of HgbA1c