Effect of Supplementary Vitamins on Oxidant Gene Expression in the Lungs of Healthy Smokers

This study has been completed.
Sponsor:
Information provided by:
Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:
NCT00565214
First received: November 27, 2007
Last updated: October 27, 2010
Last verified: October 2010
  Purpose

Smoking damages the airway epithelium. The major mechanism by which this is done is by molecules called free radicals. Our body attempts to deal with these damaging molecules in two ways. One mechanism is via the presence of protective anti-oxidant vitamins and the other is via proteins that are produced by the body to convert free radicals to safer, less reactive molecules. Vitamins in our diet play a significant role in antioxidant defenses by directly neutralizing the damaging free-radicals and by providing co-factors to cellular proteins that neutralize the free radicals. This project is designed to look at the effects of giving individuals supplemental vitamins to see if it improves their defenses against oxidant insults. The investigators plan to look at the effects of these supplements over a 30 day period and monitor the effects by measuring vitamin levels in the blood and in the lung, and by measuring the response of cells in the lung through the increase or decrease in expression of genes responsive to oxidants.

To participate in this protocol, the research subject should first be enrolled in Weill-IRB protocol #0005004439 entitled "Evaluation of the Lungs of Normal (Smokers, Ex-smokers, Non-Smokers) Individuals with Segmental Bronchopulmonary Lung Lavage, Bronchial Brushing, and Bronchial Wall Biopsy", fulfilling the inclusion/exclusion criteria of that protocol. They will be invited to participate in this Vitamin protocol only if they meet the additional inclusion/exclusion criteria of this protocol.


Condition Intervention
Chronic Obstructive Pulmonary Disease (COPD)
Dietary Supplement: Vitamin C, Vitamin E, Selenium
Dietary Supplement: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Health Services Research
Official Title: Effect of Supplementary Vitamins on Oxidant Gene Expression in the Lungs of Healthy Smokers

Resource links provided by NLM:


Further study details as provided by Weill Medical College of Cornell University:

Primary Outcome Measures:
  • F2-isoprostane and vitamin levels from blood and urine [ Time Frame: After 30 days of intervention ] [ Designated as safety issue: No ]
  • Selenium from toenail sample [ Time Frame: After 30 days of intervention ] [ Designated as safety issue: No ]
  • To observe vitamin induced fold-changed in airway epithelial oxidant-related genes known to be up- or down- regulated by cigarette smoking [ Time Frame: After 30 days of intervention ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Dietary questionnaire [ Time Frame: Completed on Day 0 ] [ Designated as safety issue: No ]
  • Smoking questionnaire [ Time Frame: Completed on Day 0 ] [ Designated as safety issue: No ]

Estimated Enrollment: 48
Study Start Date: September 2007
Study Completion Date: October 2010
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
On Day 1, Group 1 will initiate in a double-blinded fashion, a once daily vitamin combination of selenomethionine(400 μg), vitamin E(400 IU), and vitamin C (1000 mg) orally for 30 days at home. After 30 days of treatment with Vitamin supplements, the gene expression of the airway epithelium will be compared to that of the Placebo group.
Dietary Supplement: Vitamin C, Vitamin E, Selenium
The treatment plan involves the administration of a combination of 3 vitamins (vitamin C 1000 mg, vitamin E 400 IU, selenomethionine 400 μg) to study volunteers in a 2:1 randomization, Vitamins are to be taken orally, once a day, for a duration of 30 days.
Placebo Comparator: 2
On Day 1, Group 2 will initiate the placebo in a double-blinded fashion.
Dietary Supplement: Placebo
The treatment plan involves the administration of a combination of 3 placebos to be taken orally, once daily for a duration of 30 days.

Detailed Description:

The purpose of this study is to test whether dietary antioxidant supplementation can alter the expression in lung epithelial cells of genes related to oxidant response and whether this response is dependent on factors such as the individual's baseline serum antioxidant status, dietary antioxidant status, and the oxidant/anti-oxidant balance in the lung. The underlying hypothesis is that the intake of vitamins with antioxidant properties (selenomethionine, vitamin E and vitamin C) will boost the antioxidant levels of the airway epithelium sufficient to protect the epithelium from the stress of oxidants in cigarette smoke. Our prior work shows that phenotypic normal smokers (cigarette smokers with normal history, physical exam, lung function tests, and chest x-rays) have marked up and down regulation of > ~200 genes in the airway epithelium. The proposed project will build on past findings by examining whether regulation of gene expression responds to changes in nutritional status. The primary aim will be assessment of gene expression of the airway epithelium (from protocol #0005004439 entitled "Evaluation of the Lungs of Normal (Smokers, Ex-smokers, Non-Smokers) Individuals with Segmental Bronchopulmonary Lung Lavage, Bronchial Brushing, and Bronchial Wall Biopsy") obtained before and after taking standard amounts of selenomethionine, vitamin E and vitamin C, or placebo for 30 days. The secondary aims will be to evaluate the ability of vitamin supplementation to raise lung and serum vitamin levels, to reduce the oxidant stress in the lung and systemically (as measured by lung and urinary F2 isoprostane levels, respectively), and to assess the vitamin-induced change in airway epithelial gene expression in genes other than oxidant related genes.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • All study individual should be enrolled in Weill-IRB protocol #0005004439 entitled "Evaluation of the Lungs of Normal (Smokers, Ex-smokers, Non-Smokers) Individuals with Segmental Bronchopulmonary Lung Lavage, Bronchial Brushing, and Bronchial Wall Biopsy."
  • All study subjects should be able to provide informed consent.
  • Males or females ages 18 years and older.
  • Current smokers with at least a 15 pack-year history (1 pack year = on average 20 cigarettes per day for 1 year).

Exclusion Criteria:

  • Drug and/or alcohol abuse within the past six months.
  • Individuals already on supplemental vitamins.
  • Subjects intending to quit smoking in the next 30 days.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00565214

Locations
United States, New York
Weill Cornell Medical College
New York, New York, United States, 10021
Sponsors and Collaborators
Weill Medical College of Cornell University
Investigators
Principal Investigator: Ronald G Crystal, MD Weill Medical College of Cornell University
  More Information

No publications provided

Responsible Party: Ronald Crystal, Weill Cornell Medical College
ClinicalTrials.gov Identifier: NCT00565214     History of Changes
Other Study ID Numbers: 0705009179
Study First Received: November 27, 2007
Last Updated: October 27, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by Weill Medical College of Cornell University:
vitamin supplements
healthy smokers
epithelial lung tissue
bronchoscopy
antioxidant levels

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Alpha-Tocopherol
Ascorbic Acid
Tocopherols
Tocotrienols
Vitamin E
Vitamins
Antioxidants
Growth Substances
Micronutrients
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents

ClinicalTrials.gov processed this record on October 30, 2014