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

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

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).

Study Overview

• Status: Completed
• Conditions: Cigarette Smoking

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 1184

Contacts and Locations

Study Locations

• Germany
  • Hessen
    • Frankfurt, Hessen, Germany, 60596
      • Synexus Clinical Research GmbH
• Japan
  • Tokyo, Japan, 162-0053
    • Clinical Research Tokyo Hospital
• Poland
  • Kajetany, Poland, 05-830
    • BioVirtus Research Site Sp. z o.o.
• United Kingdom
  • Liverpool, United Kingdom, L22 0LG
    • Synexus, Merseyside Clinical Research Centre
• United States
  • North Carolina
    • Charlotte, North Carolina, United States, 28262
      • Rose Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult, smoking subjects willing to quit smoking with no restriction on race and ethnicities will be enrolled in this study.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Study population; 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?

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

Collaborators and Investigators

• Sponsor: Philip Morris Products S.A.
• Investigators: Principal Investigator: Christel Contzen, MD, Synexus Clinical Research GmbH; Principal Investigator: Monika Tomaszewska-Kiecana, MD, BioVirtus Research Site Sp. z o.o.; Principal Investigator: Susannah Eyre, MD, Synexus, Merseyside Clinical Research Centre; Principal Investigator: Jed Rose, PhD, Rose Research Center; Principal Investigator: Koichi Nakamura, MD, Clinical Research Tokyo Hospital

Publications and helpful links

General Publications

• Tran CT, Felber Medlin L, Lama N, Taranu B, Ng W, Haziza C, Picavet P, Baker G, Ludicke F. Biological and Functional Changes in Healthy Adult Smokers Who Are Continuously Abstinent From Smoking for One Year: Protocol for a Prospective, Observational, Multicenter Cohort Study. JMIR Res Protoc. 2019 Jun 7;8(6):e12138. doi: 10.2196/12138.
• Pouly, S., Haziza, C., Peck, M. J., & Peitsch, M. C. (2021). Clinical Assessment of ENDPs. In Toxicological Evaluation of Electronic Nicotine Delivery Products (pp. 385-459). Academic Press.

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2015
• Primary Completion (Actual): May 31, 2017
• Study Completion (Actual): April 27, 2018

Study Registration Dates

• First Submitted: April 14, 2015
• First Submitted That Met QC Criteria: April 28, 2015
• First Posted (Estimate): May 4, 2015

Study Record Updates

• Last Update Posted (Estimate): January 30, 2023
• Last Update Submitted That Met QC Criteria: January 26, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: smoking cessation; quit smoking; one year; smoking abstinence; clinical, biological and functional changes; healthy smokers
• Other Study ID Numbers: SA-SCR-01 (Other Identifier: Philip Morris Products S.A.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No