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

NCT01859390 | Completed Phase 2 Results DMC

• 2 other identifiers: 13-1557AQUADEK12K1
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 15

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.

Conditions

Cystic Fibrosis

Keywords

Antioxidants; Vitamins; Inflammation; Oxidative stress

Outcome Measures

Primary Outcomes (1)

• Change in Sputum Myeloperoxidase (MPO) Level

  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.

  Baseline (Visit 2) to Week 16 (Visit 4)

Secondary Outcomes (8)

• Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)

  18 weeks follow up

• Rate of Adverse Events (AEs) and Serious Adverse Events (SAEs)

  18 weeks follow up

• Change in Lung Function

  Baseline (Visit 2) to Week 16

• Change in Growth Endpoints

  Baseline (Visit 2) to Week 16

• Time to First Pulmonary Exacerbation

  Baseline (Visit 2) to end of follow up (Week 18)

Study Arms (2)

AquADEKs-2

EXPERIMENTAL

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; Dietary Supplement: control multivitamin

Control multivitamin

ACTIVE COMPARATOR

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

Interventions

AquADEKs-2 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.

Also known as: Antioxidant-enriched multivitamin supplement

AquADEKs-2

control multivitamin DIETARY_SUPPLEMENT

The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.

AquADEKs-2; Control multivitamin

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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:
• positive pregnancy test at Visit 1 or at Visit 2, or
• lactating or
• 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)

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Cystic Fibrosis Foundation: collaborator
• Yasoo Health: collaborator

Study Sites (15)

University Medical Center

Tucson, Arizona, 85724, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

The Nemours Children's Clinic

Orlando, Florida, 32806, United States

Location

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

Location

University of Minnesota Children's Hospital

Minneapolis, Minnesota, 55455, United States

Location

Women and Children's Hospital of Buffalo

Buffalo, New York, 14222, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232-5735, United States

Location

The University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75390, United States

Location

University of Wisconsin Hospital Center

Madison, Wisconsin, 53792, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (4)

• 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.

  PMID: 20961818 BACKGROUND

• 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.

  PMID: 17569601 BACKGROUND

• 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.

  PMID: 32622665 DERIVED

• 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.

  PMID: 29688760 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis; Inflammation

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

We did not meet the complete enrollment of 80 subjects due to the expiration dates of the antioxidant-enriched and control multivitamins produced for the study.

Results Point of Contact

• Title: Dr. Scott Sagel, Professor of Pediatrics
• Organization: University of Colorado School of Medicine

scott.sagel@ucdenver.edu

720-777-2522

Study Officials

• Scott Sagel, MD, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2013
• First Posted: May 21, 2013
• Study Start: June 1, 2013
• Primary Completion: April 1, 2015
• Study Completion: July 1, 2016
• Last Updated: July 14, 2017
• Results First Posted: June 8, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (15)