Validation of Biomarkers of Exposure and Host Response
The proposed study will evaluate biomarkers measured in exhaled breath condensate (EBC) for the purpose of assessing clinical strategies of harm reduction. It will take advantage of a recently developed device that permits collection of exhaled breath condensate reproducibly, with minimal subject effort and with no oral contamination. The major goal of the trial is to provide evidence to validate biomarkers in EBC.
This will be accomplished by collecting samples from asymptomatic smokers before and after inducing a change in their smoking habit (cessation or reduction) with the aid of partial nicotine replacement.
Measures to be made in EBC include H2O2, the most widely explored biomarker in this "body" fluid. Methods that reliably can quantify levels in normal non-smokers and in asymptomatic smokers will be used. Two fold increases in smokers have been reported by in several reports and confirmed in preliminary data by the investigators. In addition, other biomarkers of oxidant stress: TBARs, 8-isoprostane and nitrotyrosine will be quantified using standard methods.
Biomarkers quantified in EBC will be assessed for reliability (i.e. reproducibility and for sensitivity) to change and for validity (by comparison to clinically defined endpoints and previously validated measures of exposure). Reproducibility will be assessed by making repeated measurements in the same subjects on different occasions. Sensitivity to change will be assessed by comparing values before and after changing smoking habit. Finally, the validity of the biomarkers will be assessed by comparing them to previous measures of smoke exposure (CO, NNAL and NNAL-glc) and to clinically defined endpoints: symptoms, the St. George's Respiratory Questionnaire and post bronchodilator lung function. With regard to the latter measures, preliminary data indicate that symptoms can be detected in "asymptomatic" smokers and that these can change with a harm reduction strategy.
Drug: nicotine polacrilex
Drug: nicotine transdermal system
Drug: nicotine inhaler
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
|Official Title:||Validation of Biomarkers of Exposure and Host Response|
- exhaled breath hydrogen peroxide
- health status (SGRQ, CCQ, BCSS, LCQ)
- lung function
|Study Start Date:||December 2005|
|Study Completion Date:||September 2007|
|Primary Completion Date:||September 2007 (Final data collection date for primary outcome measure)|
Please refer to this study by its ClinicalTrials.gov identifier: NCT00468234
|United States, Nebraska|
|University of Nebraska Medical Center|
|Omaha, Nebraska, United States, 68198|
|Principal Investigator:||Stephen I Rennard, MD||University of Nebraska|