Reduction of Exposure, Inflammation, and Oxidative Stress Following at Least 2 Years of Switching to THS Use Compared to Cigarette Smoking

A Cross-sectional, Multi-regional Study to Demonstrate Reduction in Exposure to Key Toxicants, Oxidative Stress, and Inflammation Following at Least 2 Years of Tobacco Heating System (THS) Use Compared to Cigarette Smoking

Sponsors

Lead Sponsor: Philip Morris Products S.A.

Source Philip Morris Products S.A.
Brief Summary

This is a cross-sectional 3-group study with subjects enrolled and matched by region (Asia, Europe), age, sex, and average daily product consumption over the last 2 years as self-reported. The study will be conducted as a multi-center and multi-regional study, to demonstrate beneficial effects of switching from cigarettes to THS.

Detailed Description

The purpose of this study is primarily to demonstrate beneficial effects of switching from cigarette smoking to THS use for at least 2 years compared to cigarette smoking in a real-life condition on both inflammation and oxidative stress status as a proxy for further long-term harm in healthy subjects, using the well-established and fit-to-purpose measures of WBC and 8-epi-PGF2α, respectively, as indicators of the status of these pathways. The study aims also at demonstrating additional benefits on other mechanistic pathways along with inflammation and oxidative stress by the means of additional biomarkers of potential harm (BoPH) and to assess association with functional benefits that are expected to be responsive to the extent of exposure to harmful and potentially harmful constituents (HPHCs).

Overall Status Not yet recruiting
Start Date 2022-05-01
Completion Date 2024-02-01
Primary Completion Date 2023-10-01
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Carboxyhemoglobin (COHb) in blood Measured when subject visits study site on day 1.
Total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (total NNAL) in urine Measured when subject visits study site on day 1.
White Blood Cell total count (WBC) in blood Measured when subject visits study site on day 1.
8-epi-Prostaglandin-F2α (8-epi-PGF2α) in urine Measured when subject visits study site on day 1.
Secondary Outcome
Measure Time Frame
High-Density Lipoprotein Cholesterol (HDL-C) Measured when subject visits study site on day 1.
soluble Intercellular Adhesion Molecule-1 (sICAM-1) Measured when subject visits study site on day 1.
11-dehydrothromboxane B2 (11-DTX-B2) Measured when subject visits study site on day 1.
Augmentation Index (AIx) Measured when subject visits study site on day 1.
Forced Expiratory Volume in 1 second (FEV1) %predicted, post-bronchodilator (post-BD) Measured when subject visits study site on day 1.
Enrollment 960
Condition
Intervention

Intervention Type: Other

Intervention Name: THS use

Description: Subjects (current THS users) will continue using THS in real-life setting

Arm Group Label: THS

Intervention Type: Other

Intervention Name: Cigarette smoking

Description: Subjects (current cigarette smokers) will continue smoking cigarettes in real-life setting

Arm Group Label: Cigarette

Intervention Type: Other

Intervention Name: Smoking abstinence

Description: Subjects (former cigarette smokers) will continue smoking abstinence (confirmed by cotinine test, with a threshold of < 100 ng/mL)

Arm Group Label: SA

Eligibility

Criteria:

Inclusion Criteria: - Subject is able to understand the information provided in the main ICF and has signed the main ICF. - Subject is 30-60 years old. - Subject is healthy based on ECG, spirometry, vital signs, physical examination, medical history and Investigator's assessment. Cigarette smokers: - Has smoked ≥ 10 cigarettes/day on average (no brand restriction) over the past 2 years prior to screening. - Has smoked ≥ 10 cigarettes/day on average (no brand restriction) for at least 10 years. - Has not used other tobacco and nicotine products apart from cigarettes on a daily basis over the past 2 years prior to screening. - Smoking status will be verified by urinary cotinine test (≥ 200 ng/mL) and CO breath test (≥ 10 ppm (1)). THS users: - Has used ≥ 10 HeatSticks/day on average over the past 2 years prior to screening. - Has smoked ≥ 10 cigarettes/day on average (no brand restriction) for at least 8 years prior to switching to THS. - Has smoked < 30 cigarettes/month and used other tobacco products or e-cigarettes < daily over the past 2 years prior to screening. - Product use will be verified by urinary cotinine test (≥ 200 ng/mL) and CO breath test (< 10 ppm). Former cigarette smokers: - Has not smoked cigarettes or used any tobacco or nicotine-containing products on a daily basis over the past 2 years prior to screening. - Has smoked ≥ 10 cigarettes/day on average (no brand restriction) for at least 8 years prior to stopping smoking. - Smoking status will be verified by urinary cotinine test (< 100 ng/mL) and CO breath test (< 10 ppm). Exclusion Criteria: - As per the judgment of the Investigator, the subject cannot participate in the study for any reason (e.g., medical, psychiatric and/or social reason). The Investigator should specifically evaluate the subject's eligibility considering COVID-19 risk factors and local situation. - The subject is legally incompetent or physically/mentally incapable of giving consent (e.g., emergency situation, under guardianship, in a social or sanitary establishment, prisoner or involuntarily incarcerated). - The subject has/had clinically relevant diseases (including but not limited to gastrointestinal, renal, hepatic, neurological, hematological, endocrine, oncological, urological, immunological, pulmonary, and cardiovascular disease) or conditions that in the opinion of the investigator would jeopardize the safety of the subject or affect the validity of the study results. - The subject has abnormal findings on physical examination, ECG, vital signs, spirometry or in the medical history, deemed clinically significant by investigators. - The subject has/had within 30 days prior to screening a body temperature >37.5°C or an acute illness (e.g., upper-respiratory-tract infection, viral infection, etc.…) or the subject is confirmed or suspected active COVID-19 infection (based on the signs and symptoms observed at the time of assessment) at screening. - The subject has used any prescribed or over-the-counter systemic medication with an impact on WBC or 8-epi-PGF2α within 5 half-lives of the medication prior to enrollment in the study (please refer to Appendix B). - Subject has high blood pressure (hypertension), defined as > 139 mmHg systolic and/or > 89 mmHg diastolic or is currently treated with medication controlling high blood pressure. - The subject has (FEV1/FVC) < 0.7 and FEV1 < 80% predicted value at post-bronchodilator (BD) spirometry. - The subject has (FEV1/FVC) < 0.75 (pre-BD) and reversibility in FEV1 (that is both > 12% and > 200 mL from pre- to post-BD values). - The subject has a history of allergic reactions to salbutamol. - The subject has a body mass index (BMI) < 18.5 or ≥ 30 kg/m2. - The subject has positive alcohol and/or drug screening test results. - The subject has donated or received whole blood or blood products within 3 months prior to V1. - The subject has been previously screened for this study. - The subject is a current or former employee of the tobacco or e-cigarettes industry or of their first-degree relatives (parent, sibling, and child). - The subject is an employee of the investigational site or any other parties involved in the study or of their first-degree relatives (parent, sibling, and child). - The subject has participated in a clinical study within 3 months prior to V1. - For women only: the subject is pregnant (does have a positive pregnancy test) or breast-feeding.

Gender:

All

Minimum Age:

30 Years

Maximum Age:

60 Years

Healthy Volunteers:

Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
Christelle Haziza, PhD Study Chair Philip Morris Products S.A.
Overall Contact Contact information is only displayed when the study is recruiting subjects.
Location
Facility: Contact: Investigator:
Clintrial s.r.o. | Praha, Czechia [email protected] Roman Gregar, MD Principal Investigator
Vestra Clinics s.r.o. | Rychnov nad Kněžnou, Czechia [email protected] Ladislav Pazdera, MD Principal Investigator
emovis GmbH | Berlin, Germany [email protected] Luci Magimaiseelan, MD Principal Investigator
Sibamed GmbH & Co.KG | Leipzig, Germany [email protected] Helena Sigal, MD Principal Investigator
Centrum für Diagnostik und Gesundheit, Klinische Forschung und Entwicklung | München, Germany [email protected] Manfred Hartard, MD Principal Investigator
Praxis Reinfeld Mitte | Reinfeld, Germany [email protected] Joachim Weimer, MD Principal Investigator
Hautarzt Stuttgart - Hautarztpraxis Leitz & Kollegen | Stuttgart, Germany [email protected] Nicolas Leitz, MD Principal Investigator
Hygeia Hospital | Athens, Greece [email protected] Elias Tsougos, MD Principal Investigator
National and Kapodistrian University of Athens, Medical school, Attikon Hospital, 2nd Cardiology Department | Athens, Greece John Parissis, MD Principal Investigator
Hakata Clinic | Fukuoka, Japan [email protected] Takashi Etou, MD Principal Investigator
Nishikumamoto Hospital | Minami, Japan [email protected] Takanori Tanaka, MD Principal Investigator
Sumida Hospital | Tokyo, Japan [email protected] Takuma Yonemura, MD Principal Investigator
Location Countries

Czechia

Germany

Greece

Japan

Verification Date

2022-05-01

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 3
Arm Group

Label: Cigarette

Type: Active Comparator

Description: Current cigarette smokers

Label: THS

Type: Active Comparator

Description: THS users with a minimum of 2 years of THS use

Label: SA

Type: Active Comparator

Description: Former cigarette smokers with minimum of 2 years of smoking abstinence

Patient Data No
Study Design Info

Allocation: Non-Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Other

Masking: None (Open Label)

Masking Description: Subjects and Investigators will be unblinded to the subject's group. However, there will be a limited degree of blinding in the data review and data analysis process. In particular, sponsor and contract research organization (CRO) personnel will be blinded to the endpoints tested in the primary objective.

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