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Cardiovascular DiseaseNCT01692353

Cardiovascular Disease Biomarkers in Smokers and Moist Snuff Consumers

An observational study of Cardiovascular Disease and Cigarette Smoking, run by R.J. Reynolds Tobacco Company at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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… Read more about this study

Who is it for?
Ages 26 to 49 years, men onlyHealthy volunteers can take part
Conditions the study is for
Cardiovascular Disease, Cigarette Smoking
What is being tested?
Subject's usual brand (UB) tobacco product
How many people
168 participants
Where
1 siteUnited States
Study dates
Sep 2008to Apr 2009
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 26 to 49 years
  • Men only
  • Healthy volunteers accepted
  • Adult

Study population: Subjects were selected from a community sample of male smokers, moist snuff consumers and non-tobacco consumers. Target enrollment was 60 subjects/cohort (N=180). The age-stratification for each of the three cohorts was as follows: * Ages 26 to 31: n=15 * Ages 32 to 37: n=15 * Ages 38 to 43: n=15 * Ages 44 to 49: n=15

Who may be able to join

  • Smokers: exclusive FF (full flavor; > 13.0 mg FTC "tar" ) or FFLT (full flavor, low "tar" [6.0 to 13.0 mg FTC "tar"]) smokers who reported smoking at least 15 cigarettes daily for at least three years prior to Day 1 and whose ECO was 10 to 100 ppm (ranges of 2 to 9 ppm and 101 to 125 ppm were allowed upon joint review by the Sponsor and Investigator).
  • Moist Snuff Consumers: exclusive oral smokeless tobacco users of any brand (Copenhagen, Skoal, Grizzly, Kodiak, Timber Wolf, Longhorn, Red Man, Levi Garrett, Beech-Nut, Chattanooga Chew, Kayak, etc.), any style (snuff cut, long cut, fine cut, pouch, loose, or plug) and any flavor (natural, straight, mint, wintergreen, etc.) who reported using at least two cans or packages per week for at least three years prior to Day 1 and whose ECO was 0 to 5 ppm (a range of 6 to 10 ppm was allowed upon joint review by the Sponsor and Investigator).
  • Non-tobacco Consumers: never-smokers/never-ST users whose ECO was 0 to 5 ppm (a range of 6 to 10 ppm was allowed upon joint review by the Sponsor and Investigator).
  • Male, between 26 and 49 years of age, inclusive (on Day 1 check-in).
  • Free of clinically significant health problems in the opinion of the Investigator.
  • Forced expiratory volume exhaled in one second (FEV1) ≥70% of predicted at Screening.
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  • Willing to undergo all study procedures during confinement.
  • Not taking medication on a daily basis for chronic medical disorders deemed clinically significant by the Investigator.
  • Willing to suspend usage of daily aspirin or over-the-counter (OTC) medication seven days prior to Day 1.
  • Not taking any creatine supplements.
  • Negative tests for selected drugs of abuse and alcohol at Screening and at Day 1 check-in.
  • Able to read and comprehend questionnaires in English.
  • Able to comprehend and willing to sign an Informed Consent Form (ICF).

Who cannot join

  • At Screening, a BP that exceeds 140/90.
  • <70% predicted FEV1 from three acceptable maneuvers.
  • Unwilling to have the FMD procedure performed two or more times during confinement.
  • Unwilling to have the ABI procedure performed two times during confinement.
  • For the FMD determination, poor brachial artery visualization due to extremely deep position or severe artifacts (noise) due to overlying muscle that, in the sonographer(s)' opinion, would result in an inferior, unreadable or unobtainable brachial artery image.
  • A donation of blood from 30 days prior to Screening through Day 1, inclusive, or of plasma from two weeks prior to Screening through Day 1, inclusive.
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  • Receipt of blood products within two months prior to Day 1 check-in.
  • Evidence of visible oral cancer, as found in an oral health examination at Screening or based on oral health questions at Day 1 check-in.
  • Subject who is an employee of the clinical site.
  • Subject who has participated in any other investigational study drug or product trial in which receipt of an investigational study drug or product occurred within 30 days prior to Day 1 check-in, inclusive.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • MDS Pharma Services (US), Inc. (Currently Celerion)

    Lincoln, Nebraska, 68502

Other trials in United States

About this study

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

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.
Read the detailed 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.
Being tested
Subject's usual brand (UB) tobacco product
Keywords
Flow mediated dilation, Carotid intima-media thickness, Ankle-brachial index, Smokeless tobacco, Biological markers, Nicotine, Tobacco-specific nitrosamines, Polycyclic aromatic hydrocarbons, Aromatic amines, Mercapturic acid metabolites, Cholesterol, Blood lipids, Oxidative stress, Inflammation, Cytokines
Medical subject headings
Cardiovascular Diseases, Cigarette Smoking, Tobacco Use, Inflammation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Subject's usual brand (UB) tobacco productOther

    For SMK: UB of cigarettes; For MSC: UB of moist snuff

Study groups in NCT01692353
Study groupRoleWhat they receive
Exclusive cigarette smokers (SMK)Subject's usual brand (UB) of cigarettes
Receives: Other: Subject's usual brand (UB) tobacco product
Exclusive moist snuff consumers (MSC)Subject's usual brand (UB) of moist snuff
Receives: Other: Subject's usual brand (UB) tobacco product
Non-tobacco consumers (NTC)No use of tobacco or nicotine-containing products of any kind

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Ankle-Brachial Index (ABI-C)

    Non-invasive "functional" technique based on differential leg-arm blood pressure; aids in diagnosis of peripheral artery disease.

    Comparison of ABI-C among the three cohorts.

    Measured: Afternoon of Day 1, ~15 minutes after completion of a "tobacco product challenge"

  2. Flow-mediated Dilation (FMD-C)

    Non-invasive "functional" imaging technique to evaluate vascular tone of the brachial artery; indicator of individual's overall cardiovascular health.

    Comparison of FMD-C among the three cohorts.

    Measured: Afternoon of Day 1, ~30 minutes after completion of a "tobacco product challenge" and following ABI-C

  3. Ankle-Brachial Index (ABI-F)

    Non-invasive "functional" technique based on differential leg-arm blood pressure; aids in diagnosis of peripheral artery disease.

    Comparison of ABI-F among the three cohorts.

    Measured: Morning of Day 2 (fasting) measured immediately after vitals were obtained

  4. Flow-mediated Dilation (FMD-F)

    Non-invasive "functional" imaging technique to evaluate vascular tone of the brachial artery; indicator of individual's overall cardiovascular health.

    Comparison of FMD-F among the three cohorts.

    Measured: Morning of Day 2 (fasting) measured immediately after ABI was obtained

  5. Carotid Intima-media Thickness (CIMT-F)

    Non-invasive "morphological" imaging technique used to measure the thickness of the intima-media region of the carotid artery to detect presence/absence of atherosclerotic plaques.

    Comparison of CIMT-F among the three cohorts.

    Measured: Morning of Day 2 (fasting) immediately after FMD was obtained

  6. Urine Biomarkers of Tobacco Effect (EffBio[U]-C)

    Comparison of select CVD-related blood biomarkers among the three cohorts.

    Measured: Afternoon of Day 1, ~15 minutes after completion of a "tobacco product challenge"

  7. Urine Biomarkers of Tobacco Effect (EffBio[U]-F)

    Comparison of select CVD-related urine biomarkers among the three cohorts.

    Measured: Morning of Day 2 (fasting) from the first morning void collection

  8. Blood Biomarkers of Tobacco Effect (EffBio[B]-F)

    Comparison of select CVD-related urine biomarkers among the three cohorts.

    Measured: Morning of Day 2 (fasting) after first morning void was obtained

  9. Urine Biomarkers of Tobacco Exposure (ExpBio[U]-C)

    Comparison of tobacco-specific and tobacco-related blood biomarkers among the three cohorts.

    Measured: Afternoon of Day 1, ~15 minutes after completion of a "tobacco product challenge"

  10. Blood Biomarkers of Tobacco Exposure (ExpBio[B]-C)

    Comparison of tobacco-specific and tobacco-related blood biomarkers among the three cohorts.

    Measured: Afternoon of Day 1, ~15 minutes after completion of a "tobacco product challenge" and following the urine collection

  11. Urine Biomarkers of Tobacco Exposure (ExpBio[U]-F)

    Comparison of tobacco-specific and tobacco-related blood biomarkers among the three cohorts.

    Measured: Morning of Day 2 (fasting) from the first morning void collection

  12. Blood Biomarkers of Tobacco Exposure (ExpBio[B]-F)

    Comparison of tobacco-specific and tobacco-related blood biomarkers among the three cohorts.

    Measured: Morning of Day 2 (fasting) after first morning void was obtained

Secondary outcomes (1)

  1. Health status scores from self-administered questionnaires on health, nicotine dependence and diet

    Comparison of the self-reported health status measures between the three cohorts

    Measured: All questionnaires: Administered once on evening of Day 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Sep 2012 (estimated)
  2. Study startSep 2008
  3. Primary completionFeb 2009
  4. Study completionApr 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Cross-sectional
Enrolment
168 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01692353
Sponsor's protocol ID
RJRT-CSD0806
Status last verified
Feb 2016
First submitted
13 Aug 2012
Last updated
17 Feb 2016
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Hatsukami DK, Benowitz NL, Rennard SI, Oncken C, Hecht SS. Biomarkers to assess the utility of potential reduced exposure tobacco products. Nicotine Tob Res. 2006 Aug;8(4):600-22. doi: 10.1080/14622200600858166.

    PubMed 16920658

  • Hecht SS, Yuan JM, Hatsukami D. Applying tobacco carcinogen and toxicant biomarkers in product regulation and cancer prevention. Chem Res Toxicol. 2010 Jun 21;23(6):1001-8. doi: 10.1021/tx100056m.

    PubMed 20408564

  • Piano MR, Benowitz NL, Fitzgerald GA, Corbridge S, Heath J, Hahn E, Pechacek TF, Howard G; American Heart Association Council on Cardiovascular Nursing. Impact of smokeless tobacco products on cardiovascular disease: implications for policy, prevention, and treatment: a policy statement from the American Heart Association. Circulation. 2010 Oct 12;122(15):1520-44. doi: 10.1161/CIR.0b013e3181f432c3. Epub 2010 Sep 13. No abstract available.

    PubMed 20837898

  • Rodu B, Godshall WT. Tobacco harm reduction: an alternative cessation strategy for inveterate smokers. Harm Reduct J. 2006 Dec 21;3:37. doi: 10.1186/1477-7517-3-37.

    PubMed 17184539

  • Centers for Disease Control and Prevention (US); National Center for Chronic Disease Prevention and Health Promotion (US); Office on Smoking and Health (US). How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease: A Report of the Surgeon General. Atlanta (GA): Centers for Disease Control and Prevention (US); 2010. Available from http://www.ncbi.nlm.nih.gov/books/NBK53017/

    PubMed 21452462

  • Campbell LR, Brown BG, Jones BA, Marano KM, Borgerding MF. Study of cardiovascular disease biomarkers among tobacco consumers, part 1: biomarkers of exposure. Inhal Toxicol. 2015 Feb;27(3):149-56. doi: 10.3109/08958378.2015.1013228. Epub 2015 Mar 19.

    PubMed 25787703

  • Nordskog BK, Brown BG, Marano KM, Campell LR, Jones BA, Borgerding MF. Study of cardiovascular disease biomarkers among tobacco consumers, part 2: biomarkers of biological effect. Inhal Toxicol. 2015 Feb;27(3):157-66. doi: 10.3109/08958378.2015.1013227. Epub 2015 Mar 19.

    PubMed 25787701

  • Marano KM, Kathman SJ, Jones BA, Nordskog BK, Brown BG, Borgerding MF. Study of cardiovascular disease biomarkers among tobacco consumers. Part 3: evaluation and comparison with the US National Health and Nutrition Examination Survey. Inhal Toxicol. 2015 Feb;27(3):167-73. doi: 10.3109/08958378.2015.1009196. Epub 2015 Mar 19.

    PubMed 25787702

Questions about this trial

What is this clinical trial studying?

An observational study of Cardiovascular Disease and Cigarette Smoking, run by R.J. Reynolds Tobacco Company at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Ankle-Brachial Index (ABI-C) (time frame: Afternoon of Day 1, ~15 minutes after completion of a "tobacco product challenge"). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01692353, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2016.

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