Cardiovascular Disease Biomarkers in Smokers and Moist Snuff Consumers

This study has been completed.
Sponsor:
Collaborators:
MDS Pharma Services
Analytisch-biologisches Forschungslabor GmbH
BioClinica, Inc.
Pacific Biomarkers, Inc.
Rules-Based Medicine, Inc.
Information provided by (Responsible Party):
R.J. Reynolds Tobacco Company
ClinicalTrials.gov Identifier:
NCT01692353
First received: August 13, 2012
Last updated: September 20, 2012
Last verified: August 2012
  Purpose

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.

Condition Intervention
Cardiovascular Disease
Cigarette Smoking
Other: Subject's usual brand (UB) tobacco product

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Evaluation of Cardiovascular Disease Biomarkers in Exclusive Smokers and Exclusive Moist Snuff Consumers

Resource links provided by NLM:


Further study details as provided by R.J. Reynolds Tobacco Company:

Primary Outcome Measures:
  • Ankle-Brachial Index (ABI-C) [ Time Frame: Afternoon of Day 1, ~15 minutes after completion of a "tobacco product challenge" ] [ Designated as safety issue: No ]

    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.


  • Flow-mediated Dilation (FMD-C) [ Time Frame: Afternoon of Day 1, ~30 minutes after completion of a "tobacco product challenge" and following ABI-C ] [ Designated as safety issue: No ]

    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.


  • Ankle-Brachial Index (ABI-F) [ Time Frame: Morning of Day 2 (fasting) measured immediately after vitals were obtained ] [ Designated as safety issue: No ]

    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.


  • Flow-mediated Dilation (FMD-F) [ Time Frame: Morning of Day 2 (fasting) measured immediately after ABI was obtained ] [ Designated as safety issue: No ]

    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.


  • Carotid Intima-media Thickness (CIMT-F) [ Time Frame: Morning of Day 2 (fasting) immediately after FMD was obtained ] [ Designated as safety issue: No ]

    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.


  • Urine Biomarkers of Tobacco Effect (EffBio[U]-C) [ Time Frame: Afternoon of Day 1, ~15 minutes after completion of a "tobacco product challenge" ] [ Designated as safety issue: No ]
    Comparison of select CVD-related blood biomarkers among the three cohorts.

  • Urine Biomarkers of Tobacco Effect (EffBio[U]-F) [ Time Frame: Morning of Day 2 (fasting) from the first morning void collection ] [ Designated as safety issue: No ]
    Comparison of select CVD-related urine biomarkers among the three cohorts.

  • Blood Biomarkers of Tobacco Effect (EffBio[B]-F) [ Time Frame: Morning of Day 2 (fasting) after first morning void was obtained ] [ Designated as safety issue: No ]
    Comparison of select CVD-related urine biomarkers among the three cohorts.

  • Urine Biomarkers of Tobacco Exposure (ExpBio[U]-C) [ Time Frame: Afternoon of Day 1, ~15 minutes after completion of a "tobacco product challenge" ] [ Designated as safety issue: No ]
    Comparison of tobacco-specific and tobacco-related blood biomarkers among the three cohorts.

  • Blood Biomarkers of Tobacco Exposure (ExpBio[B]-C) [ Time Frame: Afternoon of Day 1, ~15 minutes after completion of a "tobacco product challenge" and following the urine collection ] [ Designated as safety issue: No ]
    Comparison of tobacco-specific and tobacco-related blood biomarkers among the three cohorts.

  • Urine Biomarkers of Tobacco Exposure (ExpBio[U]-F) [ Time Frame: Morning of Day 2 (fasting) from the first morning void collection ] [ Designated as safety issue: No ]
    Comparison of tobacco-specific and tobacco-related blood biomarkers among the three cohorts.

  • Blood Biomarkers of Tobacco Exposure (ExpBio[B]-F) [ Time Frame: Morning of Day 2 (fasting) after first morning void was obtained ] [ Designated as safety issue: No ]
    Comparison of tobacco-specific and tobacco-related blood biomarkers among the three cohorts.


Secondary Outcome Measures:
  • Health status scores from self-administered questionnaires on health, nicotine dependence and diet [ Time Frame: All questionnaires: Administered once on evening of Day 1 ] [ Designated as safety issue: No ]
    Comparison of the self-reported health status measures between the three cohorts


Other Outcome Measures:
  • Buccal cells [ Time Frame: Day 2 (fasting) ] [ Designated as safety issue: No ]
    Determination of the feasibility and utility of using buccal cells to distinguish DNA methylation and gene expression differences (conducted as a post-hoc evaluation)


Biospecimen Retention:   Samples Without DNA

Biospecimens to be retained include: serum, plasma, and urine.


Enrollment: 168
Study Start Date: September 2008
Study Completion Date: April 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Exclusive cigarette smokers (SMK)
Subject's usual brand (UB) of cigarettes
Other: Subject's usual brand (UB) tobacco product
For SMK: UB of cigarettes; For MSC: UB of moist snuff
Exclusive moist snuff consumers (MSC)
Subject's usual brand (UB) of moist snuff
Other: Subject's usual brand (UB) tobacco product
For SMK: UB of cigarettes; For MSC: UB of moist snuff
Non-tobacco consumers (NTC)
No use of tobacco or nicotine-containing products of any kind

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   26 Years to 49 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
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
Criteria

Inclusion Criteria:

  • 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.
  • 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).

Exclusion Criteria:

  • 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.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01692353

Locations
United States, Nebraska
MDS Pharma Services (US), Inc. (Currently Celerion)
Lincoln, Nebraska, United States, 68502
Sponsors and Collaborators
R.J. Reynolds Tobacco Company
MDS Pharma Services
Analytisch-biologisches Forschungslabor GmbH
BioClinica, Inc.
Pacific Biomarkers, Inc.
Rules-Based Medicine, Inc.
Investigators
Study Director: David L Heavner, MS R.J. Reynolds Tobacco Company
Principal Investigator: Buddy G Brown, MS R.J. Reynolds Tobacco Company
Principal Investigator: Bobbette A Jones, DrPH, CCRP R.J. Reynolds Tobacco Company
  More Information

Publications:
Responsible Party: R.J. Reynolds Tobacco Company
ClinicalTrials.gov Identifier: NCT01692353     History of Changes
Other Study ID Numbers: RJRT-CSD0806
Study First Received: August 13, 2012
Last Updated: September 20, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by R.J. Reynolds Tobacco Company:
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

Additional relevant MeSH terms:
Cardiovascular Diseases

ClinicalTrials.gov processed this record on August 20, 2014