A Smoking Cessation Study to Understand the Biological and Functional Changes After One Year of Smoking Cessation

Study Overview
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Brief Summary
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The purpose of this study was to understand the biological and functional changes after one year of smoking cessation and to collect data on a broad range of biomarkers of exposure (BoExp) and biomarkers of effect (BoE).

Detailed Description
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This was a 12 month, multi-region, multi-center, ambulatory study conducted in the US, Japan and Europe. Smokers who were willing to quit smoking within the next 30 days at the Screening Visit were enrolled to reach approximately 950 subjects continuously abstinent from smoking from Actual Quit Date (AQD) onwards at week 2, in order to achieve at least 190 successful quitters expected to complete the study. Once approximately 950 subjects reached week 2, screening and enrollment were stopped. Compliance with smoking abstinence was verified by self-reporting, CO breath tests, and urine cotinine tests. Smokers who were not continuously abstinent from smoking [i.e., free from tobacco product use (e.g., CC, pipes, cigars, snus) or any nicotine-containing product (including electronic cigarettes) other than nicotine replacement therapy (NRT)] from their AQD onwards were discontinued from the study. At the end of the study, 358 subjects were verified as continuously abstinent from their AQD.

Official Title
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A Multi-center, Multi-region Smoking Cessation Study to Understand the Biological and Functional Changes Related to Smoking Cessation in Healthy Smokers Who Are Continuously Abstinent From Smoking for One Year

Conditions
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Cigarette Smoking

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Current healthy smoker as judged by the Principal Investigator(s) or designee(s). Subject is aged from 30 to 65 years old (inclusive). Subject has smoked for at least the last 10 years. Subject smoked more than 10 cigarettes/day on average over the last year. Subject is willing to quit smoking within the next 30 days. Exclusion Criteria: Subject has clinically relevant medical conditions that in the opinion of the Investigators would jeopardize the safety of the participant or affect the validity of the study results. Subject has Forced Expiratory Volume in 1 second/Forced Vital Capacity(FEV1/FVC) < 0.7 and FEV1 < 80% predicted value at post-bronchodilator spirometry. Subject with FEV1/FVC < 0.75 (post-bronchodilator) and reversibility in FEV1 that is both > 12% and > 200 ml from pre- to post-bronchodilator values. Subject who took or is taking concomitant medication which may have an impact on the biomarkers of effect. Female subject is pregnant or is a breast-feeding.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Study population<br>Adult smokers who are willing to quit smoking within the next 30 days at the Screening Visit will be asked to continuously quit smoking for 1 year. Smokers who are not continuously abstinent from smoking or any nicotine/tobacco containing product from the actual quit date will be discontinued from the study. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| High Density Lipoprotein C (HDL-C). | Concentrations of HDL-C measured in serum. Mean values are provided as descriptive statistics. | Baseline; 6 month; 12 month | 
| Low-density Lipoprotein Cholesterol (LDL-C) | Concentrations of LDL-C measured in serum. Mean values are provided as descriptive statistics. | Baseline; 6 month; 12 month | 
| Apo A1 | Concentrations of Apolipoprotein A1 measured in serum. Mean values are provided as descriptive statistics. | Baseline; 6 month; 12 month | 
| Apo B | Concentrations of Apolipoprotein B measured in serum. Mean values are provided as descriptive statistics. | Baseline; 6 month; 12 month | 
| White Blood Cells (WBC). | Concentrations of WBC measured in blood. Mean values are provided as descriptive statistics. | Baseline; 6 month; 12 month | 
| Hs-CRP | Concentrations of high sensitivity C-reactive protein (hs-CRP) measured in serum. Geometric mean values are provided as descriptive statistics. | Baseline; 6 month; 12 month | 
| Homocysteine | Concentrations of Homocysteine measured in plasma. Geometric mean values are provided as descriptive statistics. | Baseline; 6 month; 12 month | 
| Fibrinogen | Concentrations of Fibrinogen measured in plasma. Geometric mean values are provided as descriptive statistics. | Baseline; 6 month; 12 month | 
| Platelets | Concentrations of Platelets measured in plasma. Geometric mean values are provided as descriptive statistics. | Baseline; 6 month; 12 month | 
| 11-dehydrothromboxane B2 (11-DTXB2). | Concentrations measured in urine and expressed as concentration adjusted for creatinine. Geometric mean values are provided as descriptive statistics. | Baseline; 6 month; 12 month | 
| 8-epi-prostaglandin F2α (8-epi-PGF2α). | Concentrations of 8-epi-PGF2α measured in urine and expressed as concentration adjusted for creatinine. Geometric Means are provided as descriptive statistics. | Baseline; 6 month; 12 month | 
| MPO | Concentrations of Myeloperoxidase measured in serum. Geometric mean values are provided as descriptive statistics. | Baseline; 6 month; 12 month | 
| Soluble Intercellular Adhesion Molecule 1 (sICAM-1). | Concentrations of sICAM-1 measured in serum. Geometric mean values are provided as descriptive statistics. | Baseline; 6 month; 12 month | 
| Albumin | Concentrations of Albumin measured in urine and expressed as concentration adjusted for creatinine. Geometric mean values are provided as descriptive statistics. | Baseline; 6 month; 12 month | 
| Carboxyhemoglobin (COHb). | Carboxyhemoglobin (COHb) is assayed from whole blood. Expressed as % of saturation of hemoglobin. Geometric means are provided as descriptive statistics. | Baseline; 6 month; 12 month | 
| HbA1c | Glycosylated hemoglobin (HbA1c) is assayed from whole blood. Geometric means are provided as descriptive statistics. | Baseline; 6 month; 12 month | 
| Forced Expiratory Volume in 1 Second (FEV1), Pre-bronchodilator and Expressed as Percentage Predicted (FEV1 %Pred). | FEV1 pre-bronchodilator and expressed as percentage predicted (FEV1 %pred). Mean values are provided as descriptive statistics. Spirometry is a physiological test that measures how an individual inhales or exhales volumes of air as a function of time. The primary signal measured in spirometry may be volume or flow. The forced expiratory volume (FEV) in one second is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. | Baseline; 6 month; 12 month | 
| FEV1 Post-bronchodilator and Expressed as Percentage Predicted (FEV1 %Pred). | FEV1 post-bronchodilator and expressed as percentage predicted (FEV1 %pred). Mean values are provided as descriptive statistics. Spirometry is a physiological test that measures how an individual inhales or exhales volumes of air as a function of time. The primary signal measured in spirometry may be volume or flow. The forced expiratory volume (FEV) in one second is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. | Baseline; 6 month; 12 month | 
| Forced Vital Capacity (FVC) Pre-bronchodilator, Expressed as Percentage Predicted (FVC %Pred). | Pre-bronchodilator Forced Vital Capacity, expressed as percentage predicted (FVC %pred). Mean values are provided as descriptive statistics. Spirometry is a physiological test that measures how an individual inhales or exhales volumes of air as a function of time. The primary signal measured in spirometry may be volume or flow. The forced vital capacity (FVC) is the maximal volume of air exhaled with maximally forced effort from a maximal inspiration. | Baseline; 6 month; 12 month | 
| FVC Post-bronchodilator, Expressed as Percentage Predicted (FVC %Pred). | Post-bronchodilator Forced Vital Capacity, expressed as percentage predicted (FVC %pred). Mean values are provided as descriptive statistics. Spirometry is a physiological test that measures how an individual inhales or exhales volumes of air as a function of time. The primary signal measured in spirometry may be volume or flow. The forced vital capacity (FVC) is the maximal volume of air exhaled with maximally forced effort from a maximal inspiration. | Baseline; 6 month; 12 month | 
| FEV1/FVC Pre-bronchodilator Expressed as a Ratio | Pre-bronchodilator FEV1/FVC expressed as a ratio. Mean values are provided as descriptive statistics. Spirometry is a physiological test that measures how an individual inhales or exhales volumes of air as a function of time. The primary signal measured in spirometry may be volume or flow. The forced vital capacity (FVC) is the maximal volume of air exhaled with maximally forced effort from a maximal inspiration, and the forced expiratory volume (FEV) in one second is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. | Baseline; 6 month; 12 month | 
| FEV1/FVC Post-bronchodilator Expressed as a Ratio | Post-bronchodilator FEV1/FVC expressed as a ratio. Mean values are provided as descriptive statistics. Spirometry is a physiological test that measures how an individual inhales or exhales volumes of air as a function of time. The primary signal measured in spirometry may be volume or flow. The forced vital capacity (FVC) is the maximal volume of air exhaled with maximally forced effort from a maximal inspiration, and the forced expiratory volume (FEV) in one second is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. | Baseline; 6 month; 12 month | 
| FEF 25-75 Forced Expiratory Flow, Pre-bronchodilator, Expressed as Percentage Predicted (FEF 25-75 %Pred) | Pre-bronchodilator FEF 25-75, expressed as percentage predicted (FEF 25-75 %pred). Mean values are provided as descriptive statistics. Spirometry is a physiological test that measures how an individual inhales or exhales volumes of air as a function of time. The forced expiratory flow between 25% and 75% of the FVC (FEF25-75%) is defined as the forced expiratory flow during the middle half of the FVC; the average flow from the point at which 25% of the FVC has been exhaled to the point at which 75% of the FVC has been exhaled. | Baseline; 6 month; 12 month | 
| FEF 25-75 Forced Expiratory Flow, Post-bronchodilator, Expressed as Percentage Predicted (FEF 25-75 %Pred) | Post-bronchodilator FEF 25-75, expressed as percentage predicted (FEF 25-75 %pred). Mean values are provided as descriptive statistics. Spirometry is a physiological test that measures how an individual inhales or exhales volumes of air as a function of time. The forced expiratory flow between 25% and 75% of the FVC (FEF25-75%) is defined as the forced expiratory flow during the middle half of the FVC; the average flow from the point at which 25% of the FVC has been exhaled to the point at which 75% of the FVC has been exhaled. | Baseline; 6 month; 12 month | 
| Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL). | Concentrations of Total NNAL measured in urine and expressed as concentration adjusted for creatinine. Geometric means are provided as descriptive statistics. | Baseline; 6 month; 12 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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smoking cessation, smoking abstinence, clinical, biological and functional changes, one year, healthy smokers, quit smoking