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

University of Colorado Denver (CU Denver)

Status and phase: Completed; Phase 2

Conditions: Cystic Fibrosis

Treatments: Dietary Supplement: control multivitamin; Drug: AquADEKs-2

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01859390

AQUADEK12K1 (Other Identifier)

13-1557

Details and patient eligibility

About

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.

Enrollment: 73 patients

Sex: All

Ages: 10+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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73 participants in 2 patient groups

AquADEKs-2

Experimental group

Description:

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.

Treatment:

Drug: AquADEKs-2

Dietary Supplement: control multivitamin

Control multivitamin

Active Comparator group

Description:

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.

Treatment:

Dietary Supplement: control multivitamin