Clinical trial NCT00565214: Effect of Supplementary Vitamins on Oxidant Gene Expression in the Lungs of Healthy Smokers
Official title: Effect of Supplementary Vitamins on Oxidant Gene Expression in the Lungs of Healthy Smokers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Obstructive Pulmonary Disease (COPD)
Keywords: vitamin supplements
healthy smokers
epithelial lung tissue
bronchoscopy
antioxidant levels
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
First posted: 2007-11-29
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief 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.

Eligibility 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.

Primary outcomes:
measure: The effects of the supplements on gene expression
timeFrame: After 30 days of intervention
Secondary outcomes:
measure: Vitamin supplementation
timeFrame: After 30 days of intervention
measure: Oxidant stress in the lung.
timeFrame: After 30 days of intervention
measure: Changes in airway epithelial gene expression in genes other than oxidant related genes.
timeFrame: After 30 days of intervention
Other outcomes:
Locations:
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Ronald G Crystal, MD
role: PRINCIPAL_INVESTIGATOR
References: