NCT01692353

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

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
168

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started Sep 2008

Shorter than P25 for all trials

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2008

Completed
5 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2009

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2009

Completed
3.4 years until next milestone

First Submitted

Initial submission to the registry

August 13, 2012

Completed
1 month until next milestone

First Posted

Study publicly available on registry

September 25, 2012

Completed
Last Updated

February 17, 2016

Status Verified

February 1, 2016

Enrollment Period

5 months

First QC Date

August 13, 2012

Last Update Submit

February 15, 2016

Conditions

Cardiovascular DiseaseCigarette Smoking

Keywords

Flow mediated dilationCarotid intima-media thicknessAnkle-brachial indexSmokeless tobaccoBiological markersNicotineTobacco-specific nitrosaminesPolycyclic aromatic hydrocarbonsAromatic aminesMercapturic acid metabolitesCholesterolBlood lipidsOxidative stressInflammationCytokines

Outcome Measures

Primary Outcomes (12)

  • 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.

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

  • 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.

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

  • 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.

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

  • 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.

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

  • 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.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Secondary Outcomes (1)

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

    All questionnaires: Administered once on evening of Day 1

Other Outcomes (1)

  • Buccal cells

    Day 2 (fasting)

Study Arms (3)

Exclusive cigarette smokers (SMK)

Subject's usual brand (UB) of cigarettes

Other: Subject's usual brand (UB) tobacco product

Exclusive moist snuff consumers (MSC)

Subject's usual brand (UB) of moist snuff

Other: Subject's usual brand (UB) tobacco product

Non-tobacco consumers (NTC)

No use of tobacco or nicotine-containing products of any kind

Interventions

Subject's usual brand (UB) tobacco productOTHER

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

Exclusive cigarette smokers (SMK)Exclusive moist snuff consumers (MSC)

Eligibility Criteria

Age26 Years - 49 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64)
Sampling MethodNon-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

You may qualify if:

  • 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).

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

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

Lincoln, Nebraska, 68502, United States

Location

Related Publications (8)

  • 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.

    PMID: 16920658BACKGROUND

  • 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.

    PMID: 20408564BACKGROUND

  • 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.

    PMID: 20837898BACKGROUND

  • 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.

    PMID: 17184539BACKGROUND

  • 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/

    PMID: 21452462BACKGROUND

  • 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.

    PMID: 25787703RESULT

  • 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.

    PMID: 25787701RESULT

  • 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.

    PMID: 25787702RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

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

MeSH Terms

Conditions

Cardiovascular DiseasesCigarette SmokingTobacco UseInflammation

Interventions

Tobacco Products

Condition Hierarchy (Ancestors)

Tobacco SmokingSmokingBehaviorPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Smoking DevicesManufactured MaterialsTechnology, Industry, and Agriculture

Study Officials

  • David L Heavner, MS

    R.J. Reynolds Tobacco Company

    STUDY DIRECTOR

  • Buddy G Brown, MS

    R.J. Reynolds Tobacco Company

    PRINCIPAL INVESTIGATOR

  • Bobbette A Jones, DrPH, CCRP

    R.J. Reynolds Tobacco Company

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
CROSS SECTIONAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 13, 2012

First Posted

September 25, 2012

Study Start

September 1, 2008

Primary Completion

February 1, 2009

Study Completion

April 1, 2009

Last Updated

February 17, 2016

Record last verified: 2016-02

Data Sharing

IPD Sharing
Will not share

Locations

US(1)