Development of Biomarkers of Effect From Chronic Tobacco Usage

NCT01923402 | Completed

• 1 other identifier: RJRT-CSD0906
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

This study was conducted to develop biomarkers of tobacco effect that would indicate potential harm related to tobacco consumption. To gain a better understanding of chronic effects of tobacco consumption, this cross-sectional clinical study enrolled generally healthy, adult male consumers of cigarettes (SMK), moist snuff (MSC), and no tobacco products (NTC).

Conditions

Cigarette Smoking

Keywords

Biomarkers; Metabolic Profiling; Metabolomics; Tobacco; Smokeless Tobacco; Moist Snuff

Outcome Measures

Primary Outcomes (8)

• Urinary Tobacco Exposure Biomarkers: Nicotine (NIC) and nine metabolites, Tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons, aromatic amines, mercapturic acid metabolites, and thiocyanate.

  Tobacco-specific and tobacco-related biomarkers of exposure were evaluated.

  Evening of Day -1, 24-hour urine collected within a 24 hour window prior to check-in

• Urinary Tobacco Exposure Biomarkers: Trace metals

  Tobacco-related biomarkers of exposure were evaluated.

  Morning of Day 1 (fasting) from the first morning void collection

• Buccal Cell Biomarkers

  The analyses from buccal cell biomarkers may include assessment of epigenetic changes.

  Evening of Day -1, collected ~2 hours after 8:00pm check-in and start of 24 hour fast

• Blood Biomarkers of Tobacco Exposure

  The biomarkers of tobacco exposure included Carboxyhemoglobin, Nicotine, Cotinine, and Thiocyanate.

  Morning of Day 1 (fasting) after first morning void was obtained

• Blood Biomarkers of Tobacco Effect

  The biomarkers of tobacco effect included Nitric Oxide Pathway, Coagulation Factors, Oxidative Stress, Inflammation Mediators, Lipids and Lipoproteins, and Hematology.

  Morning of Day 1 (fasting) after first morning void was obtained

• Saliva Biomarkers

  The analyses from saliva biomarkers may include assessment of epigenetic changes, cytokine profiles, and other measures to assess the effects of tobacco usage.

  Morning of Day 1 (fasting), ~30 minutes after completion of blood collection and prior to buccal cell collection

• Buccal Cell Biomarkers

  The analyses from buccal cell biomarkers may include assessment of epigenetic changes.

  Morning of Day 1 (fasting), ~30 minutes after completion of blood collection and following saliva collection

• Urinary Tobacco Exposure Biomarkers: Nicotine (NIC) and nine metabolites.

  Tobacco-specific biomarkers of exposure were evaluated.

  Day 1 (fasting), Spot-urine collected ~2 hours after collection of first morning void and immediately following saliva/buccal collection

Secondary Outcomes (1)

• Health status scores from self-administered questionnaires on health, nicotine dependence, diet history, tobacco product usage, and perceived stress.

  All questionnaires administered once on Evening of Day -1

Study Arms (3)

Exclusive cigarette smokers

Exclusive moist snuff consumers

Non-tobacco consumers

Eligibility Criteria

• Age: 35 Years - 60 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The study target population included smokers (SMK), moist snuff consumers (MSC), and non-tobacco consumers (NTC), in generally good health, as determined by the Investigator. Exclusive tobacco smokers: n=40 Moist Snuff consumers: n=40 Non-tobacco consumers: n=40

You may qualify if:

• Males between 35 and 60 years of age, inclusive;
• Met cohort-specific requirements as follows:
• Smokers: Must have been exclusive full flavor (FF) (\>13 mg FTC \[Federal Trade Commission\] "tar") or full flavor low "tar" (FFLT) (6.0 to 10.3 mg FTC "tar") smokers who self-reported smoking at least 10 cigarettes daily for at least the past three years prior to screening and whose expired carbon monoxide (ECO) is 10 to 100 parts per million (ppm) at screening and study check-in. Note: Subjects with an ECO of 2 to 9 ppm may have been included upon joint review by the Sponsor and the Investigator.
• Moist Snuff Consumers: Must have been exclusive moist snuff consumers of any brand (Copenhagen, Skoal, Grizzly, Kodiak, Timber Wolf, Longhorn, Red Man, etc.), any style (snuff cut, long cut, mid cut, fine cut, or pouch) and any flavor (natural, straight, mint, wintergreen, etc.) who reported using at least two can per week for at least the past three years prior to screening and whose ECO is 0 5 ppm at screening and study check-in. Note: Subjects with an ECO of 6 to 10 ppm may have been included upon joint review by the Sponsor and the Investigator.
• Non-Tobacco Consumers: Must have been non-consumers of any tobacco or nicotine-containing products for at least five years prior to study screening and whose ECO is 0 to 5 ppm at screening and study check-in. Note: Subjects with an ECO of 6 to 10 ppm may have been included upon joint review by the Sponsor and the Investigator.
• Subjects who are tobacco smokers: who did NOT intend to quit smoking nor intended to quit using moist snuff. "Intent to quit" was defined as planning a quit attempt within a month of screening.
• All subjects must have met the American Red Cross Blood Donation Eligibility Guidelines (64) (inclusive of, but not limited to, age, blood pressure, bleeding conditions, recent donation, and weight) and have been generally healthy and felt well with no restrictions or limitations on activities.
• Weighed at least 110 pounds.
• Had a hemoglobin \>/= 12.5 g/dL and a hematocrit \>/= 38%.
• Tested negative for drugs of abuse by urine drug screen at screening and at study check-in, unless subject was able to present proof of a corresponding prescription concomitant medication.
• Performed a negative breath alcohol test at screening and study check-in.
• Had a negative urine cotinine test at screening and study check-in for non-tobacco consumers.
• Had a positive urine cotinine test at screening and study check-in for tobacco consumers.
• Subjects must, in the opinion of the Investigator, had been free of clinically significant health problems, including oral health.
• Not taking daily medication for a chronic medical condition deemed clinically significant by the Investigator.

You may not qualify if:

• Subjects who met any of the following criteria will be excluded from the study:
• Smokers: For three years prior to the study through Day -1, the use of any tobacco- or nicotine containing product or device other than FF or FFLT tobacco-burning cigarettes, including tobacco-heating cigarettes, e cigarettes, beedis, chewing tobacco, dry snuff, moist snuff, snus, or any nicotine replacement therapy (NRT) (e.g., patch, gum, lozenge, inhaler, spray, etc.). NOTE: Subjects who have smoked \< 6 cigars in the past 12 months prior to screening would NOT have been excluded. Subjects who received short-term administration of a NRT as a temporary bridging treatment would NOT have been excluded.
• Moist Snuff Consumers: For three years prior to the study through Day -1, the use of any other tobacco- or nicotine-containing product or device other than moist snuff, including tobacco-burning cigarettes, tobacco-heating cigarettes, e-cigarettes, beedis, cigars, pipes, chewing tobacco, snus, dry snuff, or any NRT (e.g., patch, gum, lozenge, inhaler, spray, etc.). NOTE: Subjects who received short-term administration of a NRT as a temporary bridging treatment would NOT have been excluded.
• Non Tobacco Consumers: For five years prior to the study through Day -1, the use of any kind of tobacco products or the use of any non-tobacco nicotine-containing products (NRTs) or devices (e.g., e-cigarettes).
• Subjects who were tobacco consumers: expressed an interest in quitting smoking or using moist snuff (defined as planning a quit attempt within a month of screening).
• Subjects who were MSC users or non tobacco consumers: an ECO \> 5 ppm at screening or study check-in (ECO of 6 to 10 ppm may not have been excluded based on joint review by the Sponsor and Investigator).
• Subjects who were smokers: an ECO \< 10 ppm at screening or study check-in (ECO of 2 to 9 ppm may not have been excluded based on joint review by the Sponsor and Investigator).
• Any chronic illness that, in the opinion of the Investigator, is unstable.
• A temperature above 99.5° F.
• Poor peripheral venous access.
• Clinically uncontrolled hypertension (\>/= 180 mmHg systolic or \>/= 100 mmHg diastolic blood pressure).
• Diabetes mellitus (either insulin-dependent or non-insulin dependent).
• Blood sugar levels \> 130 mg/dL after the minimum 8 hour fast requested at screening.
• Peak flow ≤ 70% of predicted average peak expiratory flow (PEF) for age and height.
• Clinical manifestations of significant metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, urological, neurological, or psychiatric disorders.

Sponsors & Collaborators

• R.J. Reynolds Tobacco Company: lead

Study Sites (1)

High Point Clinical Trials Center (formerly Mendenhall Clinical Research Center)

High Point, North Carolina, 27265, United States

Location

Related Publications (3)

• Prasad GL, Jones BA, Chen P, Gregg EO. A cross-sectional study of biomarkers of exposure and effect in smokers and moist snuff consumers. Clin Chem Lab Med. 2016 Apr;54(4):633-42. doi: 10.1515/cclm-2015-0594.

  PMID: 26495926 RESULT

• Jessen WJ, Borgerding MF, Prasad GL. Global methylation profiles in buccal cells of long-term smokers and moist snuff consumers. Biomarkers. 2018 Nov;23(7):625-639. doi: 10.1080/1354750X.2018.1466367. Epub 2018 Jul 3.

  PMID: 29771158 DERIVED

• Arimilli S, Madahian B, Chen P, Marano K, Prasad GL. Gene expression profiles associated with cigarette smoking and moist snuff consumption. BMC Genomics. 2017 Feb 14;18(1):156. doi: 10.1186/s12864-017-3565-1.

  PMID: 28193179 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Blood, urine, buccal cells, and saliva

MeSH Terms

Conditions

Cigarette Smoking; Tobacco Use

Condition Hierarchy (Ancestors)

Tobacco Smoking; Smoking; Behavior

Study Officials

• Melanie Fein, MD

  Mendenhall Clinical Research Center

  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 7, 2013
• First Posted: August 15, 2013
• Study Start: June 1, 2010
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: February 19, 2016

Record last verified: 2016-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)