Effect of Supplementary Vitamins on Oxidant Gene Expression in the Lungs of Healthy Smokers
Condition: Chronic Obstructive Pulmonary Disease (COPD)
MeSH terms: Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Study type: Interventional

Summary: 
      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.
    

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.
    

Intervention name(s): Group 1; Group 2
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): 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.; The treatment plan involves the administration of a combination of 3 placebos to be taken orally, once daily for a duration of 30 days.
Other intervention name(s): Vitamin C, Vitamin E, Selenium; Placebo
Intervention MeSH terms: Vitamins; Vitamin E; Selenium
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Health Services Research
Keywords: vitamin supplements; healthy smokers; epithelial lung tissue; bronchoscopy; antioxidant levels