Validation of Biomarkers of Exposure and Host Response

NCT ID: NCT00468234

Last Updated: 2023-08-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-12-31
• Study Completion Date: 2007-09-30

Brief Summary

This study will evaluate biomarkers measured in exhaled breath condensate (EBC) to assess clinical strategies of harm reduction. It will take advantage of a recently developed device that permits collection of exhaled breath condensate reproducibly, with minimal subject effort and with no oral contamination. Samples from asymptomatic smokers before and after inducing a change in their smoking habit (cessation or reduction) with the aid of partial nicotine replacement.

Detailed Description

The proposed study will evaluate biomarkers measured in exhaled breath condensate (EBC) for the purpose of assessing clinical strategies of harm reduction. It will take advantage of a recently developed device that permits collection of exhaled breath condensate reproducibly, with minimal subject effort and with no oral contamination. The major goal of the trial is to provide evidence to validate biomarkers in EBC.

This will be accomplished by collecting samples from asymptomatic smokers before and after inducing a change in their smoking habit (cessation or reduction) with the aid of partial nicotine replacement.

Measures to be made in EBC include H2O2, the most widely explored biomarker in this "body" fluid. Methods that reliably can quantify levels in normal non-smokers and in asymptomatic smokers will be used. Two fold increases in smokers have been reported by in several reports and confirmed in preliminary data by the investigators. In addition, other biomarkers of oxidant stress: TBARs, 8-isoprostane and nitrotyrosine will be quantified using standard methods.

Biomarkers quantified in EBC will be assessed for reliability (i.e. reproducibility and for sensitivity) to change and for validity (by comparison to clinically defined endpoints and previously validated measures of exposure). Reproducibility will be assessed by making repeated measurements in the same subjects on different occasions. Sensitivity to change will be assessed by comparing values before and after changing smoking habit. Finally, the validity of the biomarkers will be assessed by comparing them to previous measures of smoke exposure (CO, NNAL and NNAL-glc) and to clinically defined endpoints: symptoms, the St. George's Respiratory Questionnaire and post bronchodilator lung function. With regard to the latter measures, preliminary data indicate that symptoms can be detected in "asymptomatic" smokers and that these can change with a harm reduction strategy.

Conditions

Cigarette Smoker

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Interventions

nicotine polacrilex

Intervention Type: DRUG

nicotine transdermal system

Intervention Type: DRUG

nicotine inhaler

Intervention Type: DRUG

Other Intervention Names

nicotine gum; patch; nicotine oral inhaler

Eligibility Criteria

Inclusion Criteria

• Subjects must be 19 years of age or older
• Have a stable smoking habit greater than three months
• Have smoked for at least 5 pack years
• Be willing to make a serious quit attempt and be willing to use nicotine replacement therapy
• Be able to give informed consent

Exclusion Criteria

• regular use of anti-inflammatory medication; presence of any inflammatory *disease of the respiratory tract including moderate or worse COPD (FEV1 < 80% predicted and FEV1/FVC ratio < 0.7) or PFT criteria for asthma (improvement in FEV1>12% of predicted and >200ml).
• Subjects with normal lung function who meet criteria for diagnosis of chronic bronchitis will be excluded.
• Subjects with stable medical conditions, excluding inflammatory lung disease, will be permitted to participate, providing anti-inflammatory therapies are not used regularly and providing there has been no change in their clinical status in the two months prior to beginning the study.

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Institute for Science and Health

UNKNOWN

Sponsor Role: collaborator

University of Nebraska

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephen I Rennard, MD

Role: PRINCIPAL_INVESTIGATOR

University of Nebraska

Locations

University of Nebraska Medical Center

Omaha, Nebraska, United States

Countries

United States

Other Identifiers

009-05

Identifier Type: -

Identifier Source: org_study_id