This proposed project is a randomized clinical trial testing whether supplementation with selenium and/or vitamin E affects pulmonary function. There is compelling evidence from observational epidemiologic studies that high antioxidant intakes are associated with reduced risks of chronic obstructive disease (COPD) and increased lung function. This proposal is an ancillary study to the multisite selenium and Vitamin E Cancer Prevention Trial (SELECT), a 4-arm placebo-controlled, double-blinded randomized trial in 32,400 men testing whether daily supplementation with vitamin E (400mg alpha-tocopherol), selenium (200 micrograms selenomethionine) or both vitamin E and selenium can prevent prostate cancer. We will enroll 3,000 SELECT participants for this respiratory ancillary study, and extend data collection to include pulmonary function, respiratory disease, and respiratory symptoms. We also will collect biological measures of nutrient exposure (serum vitamin E and selenium) and plasma lipids (total and high-density lipoprotein cholesterol) on all participants and oxidant burden (urinary F2-isoprostane) on a sub sample of heavy smokers and men with COPD. The primary outcome will be change between baseline and year 3 in forced expiratory volume in the first second (FEV1). FEV1 is a valid and reliable measure of respiratory function that strongly predicts COPD and mortality. Extensive data on diet and dietary supplement use are being collected by the SELECT parent study.
All specific aims examine pre-specified contrasts between the 4 arms of the SELECT randomized trial. The underlying hypothesis is that antioxidants will reduce the age related decline in FEV1, and thus at the 3-year follow-up FEV1 will be higher in the groups receiving antioxidant supplements compared to controls. A secondary aim considers whether the effect of supplementation is greater among smokers (high burden of exogenous oxidants) who, by purposive selection of the study sites, will comprise 25% of the sample. The proposed study addresses important and timely questions about diet and lung disease, and makes cost efficient use of the research infrastructure of SELECT. This study could have enormous public health significance, because supplementation with antioxidant nutrients would be an inexpensive and practicable means to reduce morbidity and mortality from pulmonary disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL071022-01A1
Application #
6600728
Study Section
Clinical Trials Review Committee (CLTR)
Program Officer
Croxton, Thomas
Project Start
2003-08-01
Project End
2008-07-31
Budget Start
2003-08-01
Budget End
2004-07-31
Support Year
1
Fiscal Year
2003
Total Cost
$724,307
Indirect Cost
Name
Cornell University
Department
Nutrition
Type
Other Domestic Higher Education
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
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Goodman, Phyllis J; Tangen, Catherine M; Darke, Amy K et al. (2016) Opportunities and challenges in incorporating ancillary studies into a cancer prevention randomized clinical trial. Trials 17:400
Cassano, Patricia A; Guertin, Kristin A; Kristal, Alan R et al. (2015) A randomized controlled trial of vitamin E and selenium on rate of decline in lung function. Respir Res 16:35
Tang, Wenbo; Bentley, Amy R; Kritchevsky, Stephen B et al. (2013) Genetic variation in antioxidant enzymes, cigarette smoking, and longitudinal change in lung function. Free Radic Biol Med 63:304-12
Bentley, A R; Kritchevsky, S B; Harris, T B et al. (2012) Dietary antioxidants and forced expiratory volume in 1 s decline: the Health, Aging and Body Composition study. Eur Respir J 39:979-84
Bentley, Amy R; Kritchevsky, Stephen B; Harris, Tamara B et al. (2012) Genetic variation in antioxidant enzymes and lung function. Free Radic Biol Med 52:1577-83
Agler, Anne H; Kurth, Tobias; Gaziano, J Michael et al. (2011) Randomised vitamin E supplementation and risk of chronic lung disease in the Women's Health Study. Thorax 66:320-5
Soler Artigas, MarĂ­a; Loth, Daan W; Wain, Louise V et al. (2011) Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function. Nat Genet 43:1082-90
McKeever, Tricia M; Lewis, Sarah A; Cassano, Patricia A et al. (2010) Patterns of dietary intake and relation to respiratory disease, forced expiratory volume in 1 s, and decline in 5-y forced expiratory volume. Am J Clin Nutr 92:408-15
Cassano, Patricia A (2009) Nutritional effects on asthma aetiology and progression. Thorax 64:560

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