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

NCT05385055 | Completed

• 1 other identifier: P1-RMC-03-INT
• Study Type: observational
• Target: 952
• Locations: 6 countries
• Sites: 37

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.

Conditions

Inflammation; Oxidative Stress; Smoking; Smoking Abstinence

Outcome Measures

Primary Outcomes (4)

• 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.

• 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.

• 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.

• 8-epi-Prostaglandin-F2α (8-epi-PGF2α) in urine

  Concentrations of 8-epi-PGF2α measured in urine and expressed as concentration adjusted for creatinine (pg/mg creat).

  Measured when subject visits study site on day 1.

Secondary Outcomes (5)

• 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.

Other Outcomes (10)

• Neutrophil to Lymphocyte Ratio (NLR)

  Measured when subject visits study site on day 1.

• High-sensitivity C-Reactive Protein (hs-CRP)

  Measured when subject visits study site on day 1.

• Homocysteine (HCY)

  Measured when subject visits study site on day 1.

Study Arms (3)

Cigarette

Current cigarette smokers

Other: Cigarette smoking

THS

THS users with a minimum of 2 years of THS use

Other: THS use

SA

Former cigarette smokers with minimum of 2 years of smoking abstinence

Other: Smoking abstinence

Interventions

THS use OTHER

N/A: No intervention was assigned.

THS

Cigarette smoking OTHER

N/A: No intervention was assigned.

Cigarette

Smoking abstinence OTHER

N/A: No intervention was assigned.

SA

Eligibility Criteria

• Age: 30 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• 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).

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Philip Morris Products S.A.: lead

Study Sites (37)

Medical Centre Asklepii

Kyustendil, 2600, Bulgaria

Location

Medical Centre Leo Clinic EOOD

Lovech, 5500, Bulgaria

Location

Medical Center ReSpiro

Razgrad, 7200, Bulgaria

Location

Medical Center Zara-Med EOOD

Stara Zagora, 6000, Bulgaria

Location

Private Internal ambulance

Karlovy Vary, 360 17, Czechia

Location

PreventaMed s.r.o.

Olomouc, 77900, Czechia

Location

Praglandia s.r.o.

Prague, 15000, Czechia

Location

Clintrial s.r.o.

Prague, Czechia

Location

Zdravi - fit, s.r.o.

Protivín, 398 11, Czechia

Location

Ordinance praktickeho lekai'e

Přeštice, 33401, Czechia

Location

Vestra Clinics s.r.o.

Rychnov nad Kněžnou, Czechia

Location

Velocity Clinical Research Germany GmbH

Berlin, 10787, Germany

Location

emovis GmbH

Berlin, Germany

Location

Synexus Clinical Research GmbH

Frankfurt, 60313, Germany

Location

Klinische Forschung Hamburg GmbH

Hamburg, 20253, Germany

Location

Klinische Forschung Hannover-Mitte GmbH

Hanover, 30159, Germany

Location

Klinische Forschung Karlsruhe GmbH

Karlsruhe, 76137, Germany

Location

Velocity Clinical Research Leipzig

Leipzig, 4103, Germany

Location

Centrum für Diagnostik und Gesundheit, Klinische Forschung und Entwicklung

München, Germany

Location

Schaum/Hecht_RED Institut fur medizinische Forschung und Fortbildung GmbH

Oldenburg in Holstein, 23758, Germany

Location

Praxis Reinfeld Mitte

Reinfeld, Germany

Location

Klinische Forschung Dresden GmbH

Sachsen, 1069, Germany

Location

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

Athens, Greece

Location

Aristotle University Thessaloniki/Papageorgiou Hospital

Thessaloniki, 56403, Greece

Location

Hakata Clinic

Fukuoka, Japan

Location

Yokohama Minoru Clinic

Kanagawa, 2320064, Japan

Location

Nishikumamoto Hospital

Minami, Japan

Location

OPHAC Hospital

Osaka, 5320003, Japan

Location

OCROM Clinic

Osaka, 6560853, Japan

Location

ToCROM Clinic

Tokyo, 160-0008, Japan

Location

Samoncho Clinic

Tokyo, 1600017, Japan

Location

Sumida Hospital

Tokyo, Japan

Location

Centrum Medyczne Pratia

Katowice, 40-081, Poland

Location

Clinical Medical Research Sp. z o.o.

Katowice, 40-156, Poland

Location

Tomed Tomasz Miszalski-Jamka

Krakow, 31-353, Poland

Location

Synexus Polska Sp zoo OddziaL w Lodzi

Lodz, 90-127, Poland

Location

Bioresearch Group

Nadarzyn, 05-830, Poland

Location

Related Publications (1)

• 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.

  PMID: 39882959 DERIVED

MeSH Terms

Conditions

Inflammation; Smoking

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavior

Study Officials

• Christelle Haziza, PhD

  Philip Morris Products S.A.

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2022
• First Posted: May 23, 2022
• Study Start: June 13, 2022
• Primary Completion: December 27, 2023
• Study Completion: April 23, 2024
• Last Updated: September 4, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

GR (2); JP (8); CZ (7); BU (4); DE (11); PL (5)