Effects of an Antioxidant-Enriched Multivitamin Supplement on Inflammation and Oxidative Stress in Cystic Fibrosis (AquADEKs-2)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University of Colorado, Denver
Sponsor:
Collaborators:
Cystic Fibrosis Foundation Therapeutics Incorporated
Yasoo Health
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT01859390
First received: May 17, 2013
Last updated: May 30, 2014
Last verified: May 2014
  Purpose

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. We 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.


Condition Intervention Phase
Cystic Fibrosis
Drug: AquADEKs-2
Dietary Supplement: control multivitamin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multi-Center, Randomized, Controlled, Double-Blind Study of the Effects of an Antioxidant-Enriched Multivitamin Supplement on Inflammation and Oxidative Stress in Cystic Fibrosis Patients

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • Change in Sputum Myeloperoxidase (MPO) Level [ Time Frame: Between Baseline (Visit 2) and Week 16 (Visit 4) ] [ Designated as safety issue: No ]
    The primary outcome in the study is the change in the sputum levels of MPO between baseline and week 16.


Secondary Outcome Measures:
  • Number of Adverse Events [ Time Frame: 22 weeks for each participant ] [ Designated as safety issue: Yes ]
    Incidence of adverse events including clinically significant changes in clinical safety lab values

  • Change in Systemic Antioxidant Levels [ Time Frame: Between baseline (Visit 2) and Weeks 4 and 16 ] [ Designated as safety issue: No ]
    Changes in plasma levels of carotenoids (β-carotene, lutein, zeaxanthin and lycopene), CoQ10, γ-tocopherol, and erythrocyte glutathione peroxidase activity between Baseline and Weeks 4 and 16. Analyses will be performed for absolute values and values corrected for total lipids.

  • Change in Systemic Markers of Inflammation and Oxidative Stress [ Time Frame: Between Baseline (Visit 2) and weeks 4 and 16 ] [ Designated as safety issue: No ]
    • Changes in absolute neutrophil counts, high sensitivity C-reactive protein (hs-CRP), calprotectin, serum amyloid A (SAA), and myeloperoxidase (MPO) measured in plasma between Baseline and Weeks 4 and 16
    • Changes in malondialdehyde, protein carbonyls, and total antioxidant capacity measured in plasma between Baseline and Weeks 4 and 16
    • Change in 8-iso-PGF2α measured in urine between Baseline and Week 16

  • Change in Sputum Markers of Inflammation and Oxidative Stress [ Time Frame: Between Baseline (Visit 2) and Week 16 ] [ Designated as safety issue: No ]
    • Changes in sputum levels of free neutrophil elastase activity, alpha1 antitrypsin (A1AT), secretory leukoprotease inhibitor (SLPI), Interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-α) between Baseline and Week 16
    • Changes in levels of 8-iso-PGF2α and 8-Oxo-2'-deoxyguanosine(8-OHdG) between Baseline and Week 16

  • Change in Systemic Vitamin Levels [ Time Frame: Between Baseline (Visit 2) and Weeks 4 and 16 ] [ Designated as safety issue: No ]
    • Changes in plasma levels of retinol (vitamin A), 25-hydroxy vitamin D, α- tocopherol (vitamin E), and PIVKA-II between Baseline and Weeks 4 and 16. Analyses will be performed for absolute values and values corrected for total lipids.

  • Changes in Lung Function Endpoints [ Time Frame: Between Baseline (Visit 2) and Weeks 4 and 16 ] [ Designated as safety issue: No ]
    • Change in forced expiratory volume over one second (FEV1) % predicted between Baseline and Weeks 4 and 16
    • Change in FEV1 (Liters) between Baseline and Weeks 4 and 16

  • Change in Growth Endpoints [ Time Frame: Between Baseline (Visit 2) and Week 16 ] [ Designated as safety issue: No ]
    Change in weight (kg and z-score) and BMI (kg/m2 and z-score) between Baseline and Week 16

  • Time to Pulmonary Exacerbation [ Time Frame: Between Baseline (Visit 2) and End of Follow-Up ] [ Designated as safety issue: No ]
    • Time to first acute protocol-defined pulmonary exacerbation between Baseline and end of follow up

  • Number of Pulmonary Exacerbations [ Time Frame: Baseline to end of follow up ] [ Designated as safety issue: No ]
    Number of acute pulmonary exacerbations between Baseline and end of follow up

  • Number of hospitalizations [ Time Frame: Baseline to end of followup ] [ Designated as safety issue: No ]
    Number of hospitalizations between baseline and end of follow up


Estimated Enrollment: 80
Study Start Date: June 2013
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AquADEKs-2
Two control multivitamin softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 4 weeks for the screening run in period. For those subjects randomized to the AquADEKs-2 arm, two AquADEKs-2 softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 16 weeks.
Drug: AquADEKs-2
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.
Other Name: Antioxidant-enriched multivitamin supplement
Dietary Supplement: control multivitamin
The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.
Active Comparator: Control multivitamin
Two control multivitamin softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 4 weeks for the screening run in period for all participants and for 16 weeks for those randomized to this comparative therapy.
Dietary Supplement: control multivitamin
The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.

  Eligibility

Ages Eligible for Study:   10 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • 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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01859390

Contacts
Contact: Scott Sagel, MD, PhD 720-777-2522 Scott.Sagel@childrenscolorado.org
Contact: Meg Anthony, MSW 720-777-2945 Meg.Anthony@childrenscolorado.org

Locations
United States, Arizona
University Medical Center Recruiting
Tucson, Arizona, United States, 85724
Contact: Osmara Molina, BS    520-891-6767    omolina@arc.arizona.edu   
Principal Investigator: Cori Daines, MD         
United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Meg Anthony, MSW    720-777-2945    Meg.Anthony@childrenscolorado.org   
Contact: Carol Kopecky, RT    720-777-2613    Carol.Kopecky@childrenscolorado.org   
Principal Investigator: Scott Sagel, MD         
United States, Florida
The Nemours Children's Clinic Recruiting
Orlando, Florida, United States, 32806
Contact: Omar Oquendo, NCMA,BSHM,CRC    407-650-7880    omar.oquendoflores@nemours.org   
Principal Investigator: Floyd Livingston, MD         
United States, Michigan
Children's Hospital of Michigan Recruiting
Detroit, Michigan, United States, 48201
Contact: Catherine Van Wagnen, RN, BSN    313-745-4737    cvanwag@med.wayne.edu   
Principal Investigator: Ibrahim Abdulhamid, MD         
United States, Minnesota
University of Minnesota Children's Hospital Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Denise Stacklie, RRT    612-626-9491    stack046@umn.edu   
Contact: Patricia Grover, RN    (612) 626-7425    Grove026@umn.edu   
Principal Investigator: Jordan Dunitz, MD         
United States, New York
Women and Children's Hospital of Buffalo Recruiting
Buffalo, New York, United States, 14222
Contact: Nadine Caci, RNC    716-878-7524    ncaci@upa.chob.edu   
Contact: Ali Jameeleh, RN    (716) 878-1069    jali@upa.chob.edu   
Principal Investigator: Drucy Borowitz, MD         
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Lorrie Duan, RN    513-636-7089    lorrie.duan@cchmc.org   
Contact: Beth Decker, BSN,RN    (513) 80304325    beth.decker@cchmc.org   
Principal Investigator: John Clancy, MD         
Rainbow Babies and Children's Hospital Recruiting
Cleveland, Ohio, United States, 44106
Contact: Roberta (Bobbi) Ksenich, BSN    216-844-5733    Roberta.Ksenich@UHHospitals.org   
Contact: David Weaver, RN, BSN    (216) 983-0469    David.Weaver@UHhospitals.org   
Principal Investigator: Steven Strausbaugh, MD         
Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States, 43205
Contact: Melinda Smith, RN    614-722-2607    melinda.smith@nationwidechildrens.org   
Principal Investigator: Karen McCoy, Md         
United States, Pennsylvania
Penn State Milton S. Hershey Medical Center Recruiting
Hershey, Pennsylvania, United States, 17033
Contact: Diane Kitch, RN    717-531-5646    dkitch@psu.edu   
Contact: Lisa Allwein    (717) 531-8196    lallwein@hmc.psu.edu   
Principal Investigator: Gavin Graff, MD         
Children's Hospital of Pittsburgh of UPMC Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Elizabeth Hartigan, RN, MPH, CRM    412-692-7060    elizabeth.hartigan@chp.edu   
Contact: Sandra Hurban, RN, BSN    (412) 692-7042    sandra.hurban@chp.edu   
Principal Investigator: David Orenstein, MD         
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232-5735
Contact: William Hardeman, BS    615-936-8308    william.g.hardeman@Vanderbilt.Edu   
Contact: Pamela Berry, RN    (615) 936-1826    pamela.berry@Vanderbilt.Edu   
Principal Investigator: Bonnie Slovis, MD         
United States, Texas
The University of Texas Southwestern Medical Center at Dallas Recruiting
Dallas, Texas, United States, 75390
Contact: Ashley Keller, MPH, BS    214-648-2817    Ashley.Keller@UTSouthwestern.edu   
Principal Investigator: Raksha Jain, MD, MSCI         
United States, Wisconsin
University of Wisconsin Hospital Center Recruiting
Madison, Wisconsin, United States, 53792
Contact: Linda Makholm, MT (ASCP)    608-262-0340    Lmakholm@uwhealth.org   
Principal Investigator: Michael Rock, MD         
Children's Hospital of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Patricia M Hastings    414-266-4707      
Contact: Theresa Kump, BA    (414) 337-7144    tkump@mcw.edu   
Principal Investigator: Julie Noe, MD         
Sponsors and Collaborators
University of Colorado, Denver
Cystic Fibrosis Foundation Therapeutics Incorporated
Yasoo Health
Investigators
Principal Investigator: Scott Sagel, MD, PhD University of Colorado, Denver
  More Information

Publications:
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01859390     History of Changes
Other Study ID Numbers: 13-1557, AQUADEK12K1
Study First Received: May 17, 2013
Last Updated: May 30, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by University of Colorado, Denver:
Antioxidants
Vitamins
Inflammation
Oxidative stress

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Inflammation
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 23, 2014