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Trial record 1 of 1 for:    NCT01859390
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Effects of an Antioxidant-Enriched Multivitamin Supplement on Inflammation and Oxidative Stress in Cystic Fibrosis (AquADEKs-2)

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ClinicalTrials.gov Identifier: NCT01859390
Recruitment Status : Completed
First Posted : May 21, 2013
Results First Posted : June 8, 2017
Last Update Posted : July 14, 2017
Sponsor:
Collaborators:
Cystic Fibrosis Foundation
Yasoo Health
Information provided by (Responsible Party):
University of Colorado, Denver

Tracking Information
First Submitted Date  ICMJE May 17, 2013
First Posted Date  ICMJE May 21, 2013
Results First Submitted Date  ICMJE March 10, 2017
Results First Posted Date  ICMJE June 8, 2017
Last Update Posted Date July 14, 2017
Study Start Date  ICMJE June 2013
Actual Primary Completion Date April 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 3, 2017)
Change in Sputum Myeloperoxidase (MPO) Level [ Time Frame: Baseline (Visit 2) to Week 16 (Visit 4) ]
The primary outcome is the difference in 16 week mean change in log10 sputum myeloperoxidase levels between the AquADEKs-2 arm and the Control Multivitamin arm.
Original Primary Outcome Measures  ICMJE
 (submitted: May 20, 2013)
Change in Sputum Myeloperoxidase (MPO) Level [ Time Frame: Between Baseline (Visit 2) and Week 16 (Visit 4) ]
The primary outcome in the study is the change in the sputum levels of MPO between baseline and week 16.
Change History Complete list of historical versions of study NCT01859390 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 3, 2017)
  • Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: 18 weeks follow up ]
    Incidence is defined as the number and percentage of participants with at least one event over the 18 week follow-up period.
  • Rate of Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: 18 weeks follow up ]
    Rate is defined as the number of events per participant follow-up week.
  • Change in Lung Function [ Time Frame: Baseline (Visit 2) to Week 16 ]
    Absolute Change in Forced Expiratory Volume over one second (FEV1) % predicted between Baseline and Week 16. Global Lung Initiative equations were used to calculate FEV1 %predicted.
  • Change in Growth Endpoints [ Time Frame: Baseline (Visit 2) to Week 16 ]
    Absolute change in Body Mass Index (BMI) (kg/m^2) between Baseline and Week 16.
  • Time to First Pulmonary Exacerbation [ Time Frame: Baseline (Visit 2) to end of follow up (Week 18) ]
    Median time to first pulmonary exacerbation (PEx) between baseline (Visit 2) and end of follow up (Week 18)
  • Number of Pulmonary Exacerbations [ Time Frame: Baseline (Visit 2) to end of follow up (Week 18) ]
    The total number of PEx between baseline (Visit 2) and end of follow up (Week 18).
  • Number of Participants With Pulmonary Exacerbations [ Time Frame: Baseline (Visit 2) to end of follow up (Week 18) ]
    Number (%) with at least one protocol-defined PEx between baseline (Visit 2) and end of follow up (Week 18).
  • Number of Participants Hospitalized [ Time Frame: Baseline (Visit 2) to end of followup (Week 18) ]
    Number (%) of participants with at least one hospitalization between Baseline (Visit 2) and end of follow up (Week 18).
Original Secondary Outcome Measures  ICMJE
 (submitted: May 20, 2013)
  • Number of Adverse Events [ Time Frame: 22 weeks for each participant ]
    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 ]
    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 ]
    • 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 ]
    • 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 ]
    • 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 ]
    • 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 ]
    Change in weight (kg and z-score) and BMI (kg/m2 and z-score) between Baseline and Week 16
  • Time to and Number of Pulmonary Exacerbation [ Time Frame: Between Baseline (Visit 2) and End of Follow-Up ]
    • Time to first acute protocol-defined pulmonary exacerbation between Baseline and end of follow up
    • Number of acute pulmonary exacerbations between Baseline and end of follow up
    • Number of hospitalizations between Baseline and end of follow-up
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effects of an Antioxidant-Enriched Multivitamin Supplement on Inflammation and Oxidative Stress in Cystic Fibrosis
Official Title  ICMJE 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
Brief 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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Cystic Fibrosis
Intervention  ICMJE
  • 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.
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: AquADEKs-2
    • Dietary Supplement: control multivitamin
  • 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.
    Intervention: Dietary Supplement: control multivitamin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 3, 2017)
73
Original Estimated Enrollment  ICMJE
 (submitted: May 20, 2013)
80
Actual Study Completion Date  ICMJE July 2016
Actual Primary Completion Date April 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 10 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01859390
Other Study ID Numbers  ICMJE 13-1557
AQUADEK12K1 ( Other Identifier: Medic )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Colorado, Denver
Study Sponsor  ICMJE University of Colorado, Denver
Collaborators  ICMJE
  • Cystic Fibrosis Foundation
  • Yasoo Health
Investigators  ICMJE
Principal Investigator: Scott Sagel, MD, PhD University of Colorado, Denver
PRS Account University of Colorado, Denver
Verification Date June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP