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

NCT ID: NCT05385055

Last Updated: 2024-09-04

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 952 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-06-13
• Study Completion Date: 2024-04-23

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).

Conditions

Inflammation; Oxidative Stress; Smoking; Smoking Abstinence

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Cigarette

Current cigarette smokers

Cigarette smoking

Intervention Type: OTHER

N/A: No intervention was assigned.

THS

THS users with a minimum of 2 years of THS use

THS use

Intervention Type: OTHER

N/A: No intervention was assigned.

SA

Former cigarette smokers with minimum of 2 years of smoking abstinence

Smoking abstinence

Intervention Type: OTHER

N/A: No intervention was assigned.

Interventions

THS use

N/A: No intervention was assigned.

Intervention Type: OTHER

Cigarette smoking

N/A: No intervention was assigned.

Intervention Type: OTHER

Smoking abstinence

N/A: No intervention was assigned.

Intervention Type: OTHER

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.

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Philip Morris Products S.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christelle Haziza, PhD

Role: STUDY_CHAIR

Philip Morris Products S.A.

Locations

Medical Centre Asklepii

Kyustendil, , Bulgaria

Medical Centre Leo Clinic EOOD

Lovech, , Bulgaria

Medical Center ReSpiro

Razgrad, , Bulgaria

Medical Center Zara-Med EOOD

Stara Zagora, , Bulgaria

Private Internal ambulance

Karlovy Vary, , Czechia

PreventaMed s.r.o.

Olomouc, , Czechia

Praglandia s.r.o.

Prague, , Czechia

Clintrial s.r.o.

Prague, , Czechia

Zdravi - fit, s.r.o.

Protivín, , Czechia

Ordinance praktickeho lekai'e

Přeštice, , Czechia

Vestra Clinics s.r.o.

Rychnov nad Kněžnou, , Czechia

Velocity Clinical Research Germany GmbH

Berlin, , Germany

emovis GmbH

Berlin, , Germany

Synexus Clinical Research GmbH

Frankfurt, , Germany

Klinische Forschung Hamburg GmbH

Hamburg, , Germany

Klinische Forschung Hannover-Mitte GmbH

Hanover, , Germany

Klinische Forschung Karlsruhe GmbH

Karlsruhe, , Germany

Velocity Clinical Research Leipzig

Leipzig, , Germany

Centrum für Diagnostik und Gesundheit, Klinische Forschung und Entwicklung

München, , Germany

Schaum/Hecht_RED Institut fur medizinische Forschung und Fortbildung GmbH

Oldenburg in Holstein, , Germany

Praxis Reinfeld Mitte

Reinfeld, , Germany

Klinische Forschung Dresden GmbH

Sachsen, , Germany

National and Kapodistrian University of Athens, Medical school, Attikon Hospital, 2nd Cardiology Department

Athens, , Greece

Aristotle University Thessaloniki/Papageorgiou Hospital

Thessaloniki, , Greece

Hakata Clinic

Fukuoka, , Japan

Yokohama Minoru Clinic

Kanagawa, , Japan

Nishikumamoto Hospital

Minami, , Japan

OPHAC Hospital

Osaka, , Japan

OCROM Clinic

Osaka, , Japan

ToCROM Clinic

Tokyo, , Japan

Samoncho Clinic

Tokyo, , Japan

Sumida Hospital

Tokyo, , Japan

Centrum Medyczne Pratia

Katowice, , Poland

Clinical Medical Research Sp. z o.o.

Katowice, , Poland

Tomed Tomasz Miszalski-Jamka

Krakow, , Poland

Synexus Polska Sp zoo OddziaL w Lodzi

Lodz, , Poland

Bioresearch Group

Nadarzyn, , Poland

Countries

Bulgaria; Czechia; Germany; Greece; Japan; Poland

References

Ansari SM, Leroy P, de La Bourdonnaye G, Pouly S, Reese L, Haziza C. Differences in biomarkers of potential harm after 2+ years of tobacco heating system use compared to cigarette smoking: a cross-sectional study. Biomarkers. 2025 Mar;30(2):178-191. doi: 10.1080/1354750X.2025.2461069. Epub 2025 Feb 19.

Reference Type: DERIVED

PMID: 39882959 (View on PubMed)

Other Identifiers

P1-RMC-03-INT

Identifier Type: -

Identifier Source: org_study_id