Clinical trial NCT01859390: Effects of an Antioxidant-Enriched Multivitamin Supplement on Inflammation and Oxidative Stress in Cystic Fibrosis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Keywords: Antioxidants
Vitamins
Inflammation
Oxidative stress
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: Cystic Fibrosis Foundation
name: Yasoo Health
First posted: 2013-05-21
Enrollment: 73
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change in Sputum Myeloperoxidase (MPO) Level
timeFrame: Baseline (Visit 2) to Week 16 (Visit 4)
Secondary outcomes:
measure: Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: 18 weeks follow up
measure: Rate of Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: 18 weeks follow up
measure: Change in Lung Function
timeFrame: Baseline (Visit 2) to Week 16
measure: Change in Growth Endpoints
timeFrame: Baseline (Visit 2) to Week 16
measure: Time to First Pulmonary Exacerbation
timeFrame: Baseline (Visit 2) to end of follow up (Week 18)
measure: Number of Pulmonary Exacerbations
timeFrame: Baseline (Visit 2) to end of follow up (Week 18)
measure: Number of Participants With Pulmonary Exacerbations
timeFrame: Baseline (Visit 2) to end of follow up (Week 18)
measure: Number of Participants Hospitalized
timeFrame: Baseline (Visit 2) to end of followup (Week 18)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University Medical Center
state: Arizona
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Orlando
country: United States
facility: The Nemours Children's Clinic
state: Florida
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Children's Hospital
state: Minnesota
city: Buffalo
country: United States
facility: Women and Children's Hospital of Buffalo
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Rainbow Babies and Children's Hospital
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: The University of Texas Southwestern Medical Center at Dallas
state: Texas
city: Madison
country: United States
facility: University of Wisconsin Hospital Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
Study officials:
affiliation: University of Colorado, Denver
name: Scott Sagel, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sagel SD, Sontag MK, Anthony MM, Emmett P, Papas KA. Effect of an antioxidant-rich multivitamin supplement in cystic fibrosis. J Cyst Fibros. 2011 Jan;10(1):31-6. doi: 10.1016/j.jcf.2010.09.005. Epub 2010 Oct 20.
citation: Papas KA, Sontag MK, Pardee C, Sokol RJ, Sagel SD, Accurso FJ, Wagener JS. A pilot study on the safety and efficacy of a novel antioxidant rich formulation in patients with cystic fibrosis. J Cyst Fibros. 2008 Jan;7(1):60-7. doi: 10.1016/j.jcf.2007.05.001. Epub 2007 Jun 13.
citation: Jain R, Baines A, Khan U, Wagner BD, Sagel SD. Evaluation of airway and circulating inflammatory biomarkers for cystic fibrosis drug development. J Cyst Fibros. 2021 Jan;20(1):50-56. doi: 10.1016/j.jcf.2020.06.017. Epub 2020 Jul 1.
citation: Sagel SD, Khan U, Jain R, Graff G, Daines CL, Dunitz JM, Borowitz D, Orenstein DM, Abdulhamid I, Noe J, Clancy JP, Slovis B, Rock MJ, McCoy KS, Strausbaugh S, Livingston FR, Papas KA, Shaffer ML. Effects of an Antioxidant-enriched Multivitamin in Cystic Fibrosis. A Randomized, Controlled, Multicenter Clinical Trial. Am J Respir Crit Care Med. 2018 Sep 1;198(5):639-647. doi: 10.1164/rccm.201801-0105OC.