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

Inflammation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05385055
• Other study ID #: P1-RMC-03-INT
• Status: Completed
• Start date: June 13, 2022
• Est. completion date: April 23, 2024

Study information

• Verified date: April 2024
• Source: Philip Morris Products S.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 952
• Est. completion date: April 23, 2024
• Est. primary completion date: December 27, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 30 Years to 60 Years

Eligibility

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-PGF2a 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.

Related Conditions & MeSH terms

• Inflammation
• Oxidative Stress
• Smoking
• Smoking Abstinence

Intervention

Other:
• THS use
N/A: No intervention was assigned.
• Cigarette smoking
N/A: No intervention was assigned.
• Smoking abstinence
N/A: No intervention was assigned.

Locations

Country	Name	City	State
Czechia	Clintrial s.r.o.	Praha
Czechia	Vestra Clinics s.r.o.	Rychnov nad Knežnou
Germany	emovis GmbH	Berlin
Germany	Sibamed GmbH & Co.KG	Leipzig
Germany	Centrum für Diagnostik und Gesundheit, Klinische Forschung und Entwicklung	München
Germany	Praxis Reinfeld Mitte	Reinfeld
Germany	Hautarzt Stuttgart - Hautarztpraxis Leitz & Kollegen	Stuttgart
Greece	National and Kapodistrian University of Athens, Medical school, Attikon Hospital, 2nd Cardiology Department	Athens
Japan	Hakata Clinic	Fukuoka
Japan	Nishikumamoto Hospital	Minami
Japan	Sumida Hospital	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
Philip Morris Products S.A.

Countries where clinical trial is conducted

Czechia,  Germany,  Greece,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Neutrophil to Lymphocyte Ratio (NLR)	Calculated by dividing the number of neutrophils by number of lymphocytes from serum.	Measured when subject visits study site on day 1.
Other	High-sensitivity C-Reactive Protein (hs-CRP)	Concentrations of hs-CRP (mg/dL) measured in serum.	Measured when subject visits study site on day 1.
Other	Homocysteine (HCY)	Concentrations of HCY (µmol/L) measured in plasma.	Measured when subject visits study site on day 1.
Other	Myeloperoxidase (MPO)	Concentrations of MPO (µg/L) measured in serum.	Measured when subject visits study site on day 1.
Other	Triglycerides (TG)	Concentrations of TG (mg/dL) measured in blood.	Measured when subject visits study site on day 1.
Other	Fibrinogen	Concentrations of Fibrinogen (mg/dL) measured in serum.	Measured when subject visits study site on day 1.
Other	Glycated Hemoglobin (HbA1c)	HbA1c measured in whole blood (%).	Measured when subject visits study site on day 1.
Other	Forced Expiratory Volume in 1 second/Forced Vital Capacity (FEV1/FVC) ratio	Measured with and without bronchodilator, absolute and % predicted values, where applicable.	Measured when subject visits study site on day 1.
Other	Nicotine Equivalents (NEQ) in urine (expressed as concentration adjusted to creatinine)	NEQ measured in urine and expressed as concentration adjusted for creatinine.	Measured when subject visits study site on day 1.
Other	2-Cyanoethyl Mercapturic Acid N-Acetyl-S-(2-cyanoethyl)-L-cysteine (2CyEMA)	2CyEMA measured in urine and expressed as concentration adjusted to creatinine.	Measured when subject visits study site on day 1.
Primary	Carboxyhemoglobin (COHb) in blood	Carboxyhemoglobin (COHb) is assayed from whole blood. Expressed as % of saturation of hemoglobin.	Measured when subject visits study site on day 1.
Primary	Total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (total NNAL) in urine	Concentrations of total NNAL measured in urine and expressed as concentration adjusted for creatinine (pg/mg creat).	Measured when subject visits study site on day 1.
Primary	White Blood Cell total count (WBC) in blood	Total count in blood (GI/L). Mean values are provided.	Measured when subject visits study site on day 1.
Primary	8-epi-Prostaglandin-F2a (8-epi-PGF2a) in urine	Concentrations of 8-epi-PGF2a measured in urine and expressed as concentration adjusted for creatinine (pg/mg creat).	Measured when subject visits study site on day 1.
Secondary	High-Density Lipoprotein Cholesterol (HDL-C)	Concentrations of HDL-C (mg/dL) measured in serum.	Measured when subject visits study site on day 1.
Secondary	soluble Intercellular Adhesion Molecule-1 (sICAM-1)	Concentrations of sICAM-1 (ng/mL) measured in serum.	Measured when subject visits study site on day 1.
Secondary	11-dehydrothromboxane B2 (11-DTX-B2)	Concentrations of 11-DTX-B2 measured in urine and expressed as concentration adjusted for creatinine (pg/mg creat).	Measured when subject visits study site on day 1.
Secondary	Augmentation Index (AIx)	The augmentation index (AIx) is a measure of systemic arterial stiffness, and is defined as the ratio of augmentation (? P) to central pulse pressure and expressed as percent. AIx = (?P/PP) x 100, where P = pressure and PP = Pulse Pressure.	Measured when subject visits study site on day 1.
Secondary	Forced Expiratory Volume in 1 second (FEV1) %predicted, post-bronchodilator (post-BD)	FEV1 post-bronchodilator and expressed as percentage predicted (FEV1 %pred).	Measured when subject visits study site on day 1.