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

• ClinicalTrials.gov Identifier: NCT02432729
• Recruitment Status: Completed
• First Posted: May 4, 2015
• Results First Posted: August 26, 2019
• Last Update Posted: January 30, 2023
• Sponsor: Philip Morris Products S.A.
• Information provided by (Responsible Party): Philip Morris Products S.A.

Tracking Information

• First Submitted Date: April 14, 2015
• First Posted Date: May 4, 2015
• Results First Submitted Date: April 25, 2019
• Results First Posted Date: August 26, 2019
• Last Update Posted Date: January 30, 2023
• Actual Study Start Date: May 5, 2015
• Actual Primary Completion Date: May 31, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 15, 2019)

• High Density Lipoprotein C (HDL-C). [ Time Frame: Baseline; 6 month; 12 month ]
  Concentrations of HDL-C measured in serum. Mean values are provided as descriptive statistics.
• Low-density Lipoprotein Cholesterol (LDL-C) [ Time Frame: Baseline; 6 month; 12 month ]
  Concentrations of LDL-C measured in serum. Mean values are provided as descriptive statistics.
• Apo A1 [ Time Frame: Baseline; 6 month; 12 month ]
  Concentrations of Apolipoprotein A1 measured in serum. Mean values are provided as descriptive statistics.
• Apo B [ Time Frame: Baseline; 6 month; 12 month ]
  Concentrations of Apolipoprotein B measured in serum. Mean values are provided as descriptive statistics.
• White Blood Cells (WBC). [ Time Frame: Baseline; 6 month; 12 month ]
  Concentrations of WBC measured in blood. Mean values are provided as descriptive statistics.
• Hs-CRP [ Time Frame: Baseline; 6 month; 12 month ]
  Concentrations of high sensitivity C-reactive protein (hs-CRP) measured in serum. Geometric mean values are provided as descriptive statistics.
• Homocysteine [ Time Frame: Baseline; 6 month; 12 month ]
  Concentrations of Homocysteine measured in plasma. Geometric mean values are provided as descriptive statistics.
• Fibrinogen [ Time Frame: Baseline; 6 month; 12 month ]
  Concentrations of Fibrinogen measured in plasma. Geometric mean values are provided as descriptive statistics.
• Platelets [ Time Frame: Baseline; 6 month; 12 month ]
  Concentrations of Platelets measured in plasma. Geometric mean values are provided as descriptive statistics.
• 11-dehydrothromboxane B2 (11-DTXB2). [ Time Frame: Baseline; 6 month; 12 month ]
  Concentrations measured in urine and expressed as concentration adjusted for creatinine. Geometric mean values are provided as descriptive statistics.
• 8-epi-prostaglandin F2α (8-epi-PGF2α). [ Time Frame: Baseline; 6 month; 12 month ]
  Concentrations of 8-epi-PGF2α measured in urine and expressed as concentration adjusted for creatinine. Geometric Means are provided as descriptive statistics.
• MPO [ Time Frame: Baseline; 6 month; 12 month ]
  Concentrations of Myeloperoxidase measured in serum. Geometric mean values are provided as descriptive statistics.
• Soluble Intercellular Adhesion Molecule 1 (sICAM-1). [ Time Frame: Baseline; 6 month; 12 month ]
  Concentrations of sICAM-1 measured in serum. Geometric mean values are provided as descriptive statistics.
• Albumin [ Time Frame: Baseline; 6 month; 12 month ]
  Concentrations of Albumin measured in urine and expressed as concentration adjusted for creatinine. Geometric mean values are provided as descriptive statistics.
• Carboxyhemoglobin (COHb). [ Time Frame: Baseline; 6 month; 12 month ]
  Carboxyhemoglobin (COHb) is assayed from whole blood. Expressed as % of saturation of hemoglobin. Geometric means are provided as descriptive statistics.
• HbA1c [ Time Frame: Baseline; 6 month; 12 month ]
  Glycosylated hemoglobin (HbA1c) is assayed from whole blood. Geometric means are provided as descriptive statistics.
• Forced Expiratory Volume in 1 Second (FEV1), Pre-bronchodilator and Expressed as Percentage Predicted (FEV1 %Pred). [ Time Frame: Baseline; 6 month; 12 month ]
  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.
• FEV1 Post-bronchodilator and Expressed as Percentage Predicted (FEV1 %Pred). [ Time Frame: Baseline; 6 month; 12 month ]
  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.
• Forced Vital Capacity (FVC) Pre-bronchodilator, Expressed as Percentage Predicted (FVC %Pred). [ Time Frame: Baseline; 6 month; 12 month ]
  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.
• FVC Post-bronchodilator, Expressed as Percentage Predicted (FVC %Pred). [ Time Frame: Baseline; 6 month; 12 month ]
  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.
• FEV1/FVC Pre-bronchodilator Expressed as a Ratio [ Time Frame: Baseline; 6 month; 12 month ]
  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.
• FEV1/FVC Post-bronchodilator Expressed as a Ratio [ Time Frame: Baseline; 6 month; 12 month ]
  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.
• FEF 25-75 Forced Expiratory Flow, Pre-bronchodilator, Expressed as Percentage Predicted (FEF 25-75 %Pred) [ Time Frame: Baseline; 6 month; 12 month ]
  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.
• FEF 25-75 Forced Expiratory Flow, Post-bronchodilator, Expressed as Percentage Predicted (FEF 25-75 %Pred) [ Time Frame: Baseline; 6 month; 12 month ]
  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.
• Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL). [ Time Frame: Baseline; 6 month; 12 month ]
  Concentrations of Total NNAL measured in urine and expressed as concentration adjusted for creatinine. Geometric means are provided as descriptive statistics.

Original Primary Outcome Measures (submitted: April 28, 2015)

Description of the clinical, biological and functional changes in healthy smokers who are continuously abstinent from smoking for 1 year [ Time Frame: Week 13, Week 26 and Week 52 ]

• The following endpoints included in the "smoker's health profile" will be measured: high density lipoprotein cholesterol (HDL-C) in serum, white blood cell total count (WBC) in blood, soluble intercellular adhesion molecule-1 (sICAM-1) in serum, 11-dehydrothromboxane B2 (11-DTX-B2) in urine, 8-epi-prostaglandin F2α (8-epi-PGF2α) in urine, carboxyhemoglobin (COHb) in blood, forced expiratory volume in 1 second (FEV1), total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (total NNAL) in urine.
• Additional CREs associated with respiratory, cardiovascular diseases, xenobiotics and genotoxicity together with biomarkers of exposure will be also measured in this study.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Smoking Cessation Study to Understand the Biological and Functional Changes After One Year of Smoking Cessation
• Official Title: 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
• Brief Summary: 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

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
• Study Design: Observational Model: Other; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples Without DNA

Description:

Blood and urine bio-banking samples

• 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.
• Condition: Cigarette Smoking
• Intervention: Not Provided

Study Groups/Cohorts

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.

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 15, 2019): 1184
• Original Estimated Enrollment (submitted: April 28, 2015): 950
• Actual Study Completion Date: April 27, 2018
• Actual Primary Completion Date: May 31, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 30 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany, Japan, Poland, United Kingdom, United States

Administrative Information

• NCT Number: NCT02432729
• Other Study ID Numbers: SA-SCR-01; SA-SCR-01 ( Other Identifier: Philip Morris Products S.A. )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Philip Morris Products S.A.
• Original Responsible Party: Same as current
• Current Study Sponsor: Philip Morris Products S.A.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Christelle Haziza, PhD; Philip Morris Products S.A.
• 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

• PRS Account: Philip Morris Products S.A.
• Verification Date: January 2023