Clinical trial NCT05385055: Reduction of Exposure, Inflammation, and Oxidative Stress Following At Least 2 Years of Switching to THS Use Compared to Cigarette Smoking
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Inflammation
Oxidative Stress
Smoking
Smoking Abstinence
Lead sponsor: Philip Morris Products S.A.
Sponsor class: INDUSTRY
First posted: 2022-05-23
Enrollment: 952
Sex: ALL
Minimum age (years): 30
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population was recruited through social media and traditional display advertising. The subjects included current cigarette smokers, current THS users (with a minimum of 2 years THS use), and former cigarette smokers (with a minimum of 2 years of smoking abstinence).

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).

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.

Primary outcomes:
measure: Carboxyhemoglobin (COHb) in blood
timeFrame: Measured when subject visits study site on day 1.
measure: Total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (total NNAL) in urine
timeFrame: Measured when subject visits study site on day 1.
measure: White Blood Cell total count (WBC) in blood
timeFrame: Measured when subject visits study site on day 1.
measure: 8-epi-Prostaglandin-F2α (8-epi-PGF2α) in urine
timeFrame: Measured when subject visits study site on day 1.
Secondary outcomes:
measure: High-Density Lipoprotein Cholesterol (HDL-C)
timeFrame: Measured when subject visits study site on day 1.
measure: soluble Intercellular Adhesion Molecule-1 (sICAM-1)
timeFrame: Measured when subject visits study site on day 1.
measure: 11-dehydrothromboxane B2 (11-DTX-B2)
timeFrame: Measured when subject visits study site on day 1.
measure: Augmentation Index (AIx)
timeFrame: Measured when subject visits study site on day 1.
measure: Forced Expiratory Volume in 1 second (FEV1) %predicted, post-bronchodilator (post-BD)
timeFrame: Measured when subject visits study site on day 1.
Other outcomes:
measure: Neutrophil to Lymphocyte Ratio (NLR)
timeFrame: Measured when subject visits study site on day 1.
measure: High-sensitivity C-Reactive Protein (hs-CRP)
timeFrame: Measured when subject visits study site on day 1.
measure: Homocysteine (HCY)
timeFrame: Measured when subject visits study site on day 1.
measure: Myeloperoxidase (MPO)
timeFrame: Measured when subject visits study site on day 1.
measure: Triglycerides (TG)
timeFrame: Measured when subject visits study site on day 1.
measure: Fibrinogen
timeFrame: Measured when subject visits study site on day 1.
measure: Glycated Hemoglobin (HbA1c)
timeFrame: Measured when subject visits study site on day 1.
measure: Forced Expiratory Volume in 1 second/Forced Vital Capacity (FEV1/FVC) ratio
timeFrame: Measured when subject visits study site on day 1.
measure: Nicotine Equivalents (NEQ) in urine (expressed as concentration adjusted to creatinine)
timeFrame: Measured when subject visits study site on day 1.
measure: 2-Cyanoethyl Mercapturic Acid N-Acetyl-S-(2-cyanoethyl)-L-cysteine (2CyEMA)
timeFrame: Measured when subject visits study site on day 1.
Locations:
city: Kjustendil
country: Bulgaria
facility: Medical Centre Asklepii
city: Lovech
country: Bulgaria
facility: Medical Centre Leo Clinic EOOD
city: Razgrad
country: Bulgaria
facility: Medical Center ReSpiro
city: Stara Zagora
country: Bulgaria
facility: Medical Center Zara-Med EOOD
city: Karlovy Vary
country: Czechia
facility: Private Internal ambulance
city: Olomouc
country: Czechia
facility: PreventaMed s.r.o.
city: Prague
country: Czechia
facility: Praglandia s.r.o.
city: Praha
country: Czechia
facility: Clintrial s.r.o.
city: Protivín
country: Czechia
facility: Zdravi - fit, s.r.o.
city: Přeštice
country: Czechia
facility: Ordinance praktickeho lekai'e
city: Rychnov nad Kněžnou
country: Czechia
facility: Vestra Clinics s.r.o.
city: Berlin
country: Germany
facility: Velocity Clinical Research Germany GmbH
city: Berlin
country: Germany
facility: emovis GmbH
city: Frankfurt
country: Germany
facility: Synexus Clinical Research GmbH
city: Hamburg
country: Germany
facility: Klinische Forschung Hamburg GmbH
city: Hannover
country: Germany
facility: Klinische Forschung Hannover-Mitte GmbH
city: Karlsruhe
country: Germany
facility: Klinische Forschung Karlsruhe GmbH
city: Leipzig
country: Germany
facility: Velocity Clinical Research Leipzig
city: München
country: Germany
facility: Centrum für Diagnostik und Gesundheit, Klinische Forschung und Entwicklung
city: Oldenburg In Holstein
country: Germany
facility: Schaum/Hecht_RED Institut fur medizinische Forschung und Fortbildung GmbH
city: Reinfeld
country: Germany
facility: Praxis Reinfeld Mitte
city: Sachsen
country: Germany
facility: Klinische Forschung Dresden GmbH
city: Athens
country: Greece
facility: National and Kapodistrian University of Athens, Medical school, Attikon Hospital, 2nd Cardiology Department
city: Thessaloníki
country: Greece
facility: Aristotle University Thessaloniki/Papageorgiou Hospital
city: Fukuoka
country: Japan
facility: Hakata Clinic
city: Kanagawa
country: Japan
facility: Yokohama Minoru Clinic
city: Minami
country: Japan
facility: Nishikumamoto Hospital
city: Osaka
country: Japan
facility: OPHAC Hospital
city: Osaka
country: Japan
facility: OCROM Clinic
city: Tokyo
country: Japan
facility: ToCROM Clinic
city: Tokyo
country: Japan
facility: Samoncho Clinic
city: Tokyo
country: Japan
facility: Sumida Hospital
city: Katowice
country: Poland
facility: Centrum Medyczne Pratia
city: Katowice
country: Poland
facility: Clinical Medical Research Sp. z o.o.
city: Kraków
country: Poland
facility: Tomed Tomasz Miszalski-Jamka
city: Nadarzyn
country: Poland
facility: Bioresearch Group
city: Łódź
country: Poland
facility: Synexus Polska Sp zoo OddziaL w Lodzi
Study officials:
affiliation: Philip Morris Products S.A.
name: Christelle Haziza, PhD
role: STUDY_CHAIR
References: