Cardiovascular Disease Biomarkers in Smokers and Moist Snuff Consumers

Cardiovascular Disease Clinical Trial

Official title: Evaluation of Cardiovascular Disease Biomarkers in Exclusive Smokers and Exclusive Moist Snuff Consumers

Status Completed

Clinical Trial Summary

This cross-sectional study was primarily a cardiovascular disease (CVD) study designed a) to compare selected CVD biomarker data between subjects who were long-term consumers of cigarettes or moist snuff and non-consumers of tobacco and b) to identify principal endpoints related to CVD risk that differed among the three tobacco-use cohorts. The following assessments provided the primary study endpoints for comparative analyses between the cohorts:

1. CVD-related physiological assessments: Flow-mediated dilation (FMD), carotid intima-media thickness (CIMT), ankle-brachial index (ABI), spirometry and expired carbon monoxide (ECO).

2. CVD-related biomarker assessments in blood and urine (biomarkers of tobacco effect).

3. Biomarkers of tobacco exposure in urine and blood.

Clinical Trial Description

This single site, observational study will provide an increased understanding of how consumption of different tobacco products (i.e., cigarettes and moist snuff compared to no tobacco use) affects 1) CVD-related physiological assessments and 2) CVD-related biomarkers of tobacco effect (i.e., proteins, lipids, and cellular components). A recent policy statement from the American Heart Association provides a review and analysis of the impact of smokeless (ST) use on cardiovascular disease (CVD) (Piano et al. 2010). The authors acknowledge that the evidence is consistent with the suggestion that the cardiovascular risks from ST products are markedly lower than those from cigarette smoking. Despite the potential risk reduction in transitioning from cigarettes to ST consumption, few studies have directly compared biomarkers of tobacco effect (BioEff) among smokers, moist snuff consumers (MSC) and non-tobacco consumers (NTC).

Furthermore, this study will measure biomarkers of tobacco exposure to assess their ability to differentiate the three tobacco consumer groups (smokers, moist snuff consumers, non-tobacco consumers) based on product use. Estimating exposures to combustion-related compounds found in tobacco smoke is best accomplished using biomarkers. A key advantage of human exposure biomarkers is that they are considered reliable metrics of the levels of exposure that consumers actually experience when using tobacco products (Hecht et al., 2010). Because combustion does not occur during ST use, ST products lack most of the combustion-related compounds found in tobacco smoke. Biomarker differences found between different tobacco use groups to harmful or potentially harmful constituents may indicate differences in subsequent health risks (Rodu and Godshall, 2006; Hatsukami et al., 2006).

Epidemiological data demonstrate that the health risks associated with cigarettes are significantly greater than those associated with the use of non-combustible tobacco and nicotine products (Surgeon General, 2010). On a relative risk continuum, cigarette smoking presents a significantly greater risk to tobacco users than use of non-combustible smokeless products. ST products, which are consumed orally, do no generate chemicals associated with the burning of tobacco, and thus, present a reduced toxicant profile compared to smoking.

To address the purpose and objectives of this study, the study was conducted as follows:

• Subjects were consented for the study prior to any procedures being performed and screened on study-specific inclusion/exclusion criteria to determine subject eligibility (within 28 days of study check-in).

• Eligible subjects were admitted to the clinical research unit between 12:00 noon and 5:00 p.m. on Day 1 and confined for one overnight stay (approximately 18-23 hours).

• After all study procedures were completed on Day 1 and Day 2, appropriate basic safety assessments were made and subjects were discharged approximately at 12:00 noon on Day 2.

A brief description of the study procedures performed is listed below.

• After check-in on Day 1, eligible subjects observed a 45-minute tobacco abstention period, followed by use of a single unit of their usual brand (UB) tobacco product, referred to as a "Challenge." For smokers, the "challenge" was smoking one UB cigarette in their usual manner; for moist snuff consumers, a 30-minute use of one typical pinch of their UB moist snuff.

• Fifteen minutes after the end of UB use, the following procedures were performed sequentially: ECO; blood samples for biomarkers of exposure (serum nicotine and cotinine, percent carboxyhemoglobin in whole blood); and ABI.

• At 30 minutes post-UB use, FMD was measured followed by administration of health-related questionnaires. The non-tobacco consumers had no product "Challenge". The completion of study questionnaires served as the reference point for collection of ECO, ABI and FMD.

• Blood biomarkers of tobacco exposure were collected on Day 1 following product "Challenge" and on Day 2 following an overnight tobacco abstention and fast.

• Urine biomarkers of tobacco exposure and effect were collected on both Day 1 post-"Challenge" and on Day 2 fasting.

• Blood biomarkers of tobacco effect were only collected on Day 2 fasting, followed by the re-assessment of the physiological measures (ECO, ABI, FMD) and assessment of CIMT. ;

Study Design

Observational Model: Cohort, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases
• Cigarette Smoking

• NCT number: NCT01692353
• Study type: Observational
• Source: R.J. Reynolds Tobacco Company
• Status: Completed
• Phase: N/A
• Start date: September 2008
• Completion date: April 2009