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

NCT ID: NCT01859390

Last Updated: 2017-07-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 73 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-30
• Study Completion Date: 2016-07-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

AquADEKs-2

Intervention Type: 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.

control multivitamin

Intervention Type: DIETARY_SUPPLEMENT

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

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.

Group Type: ACTIVE_COMPARATOR

control multivitamin

Intervention Type: DIETARY_SUPPLEMENT

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

Interventions

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.

Intervention Type: DRUG

control multivitamin

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

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

Antioxidant-enriched multivitamin supplement

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

• Minimum Eligible Age: 10 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cystic Fibrosis Foundation

OTHER

Sponsor Role: collaborator

Yasoo Health

INDUSTRY

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Scott Sagel, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

University Medical Center

Tucson, Arizona, United States

Children's Hospital Colorado

Aurora, Colorado, United States

The Nemours Children's Clinic

Orlando, Florida, United States

Children's Hospital of Michigan

Detroit, Michigan, United States

University of Minnesota Children's Hospital

Minneapolis, Minnesota, United States

Women and Children's Hospital of Buffalo

Buffalo, New York, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Rainbow Babies and Children's Hospital

Cleveland, Ohio, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

The University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, United States

University of Wisconsin Hospital Center

Madison, Wisconsin, United States

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 20961818 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17569601 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32622665 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29688760 (View on PubMed)

Other Identifiers

AQUADEK12K1

Identifier Type: OTHER

Identifier Source: secondary_id

13-1557

Identifier Type: -

Identifier Source: org_study_id