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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05385055
Recruitment Status : Recruiting
First Posted : May 23, 2022
Last Update Posted : July 13, 2022
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Inflammation Oxidative Stress Smoking Smoking Abstinence Other: THS use Other: Cigarette smoking Other: Smoking abstinence Not Applicable

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 960 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
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.
Primary Purpose: Other
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
Actual Study Start Date : June 13, 2022
Estimated Primary Completion Date : October 2023
Estimated Study Completion Date : February 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Smoking

Arm Intervention/treatment
Active Comparator: Cigarette
Current cigarette smokers
Other: Cigarette smoking
Subjects (current cigarette smokers) will continue smoking cigarettes in real-life setting

Active Comparator: THS
THS users with a minimum of 2 years of THS use
Other: THS use
Subjects (current THS users) will continue using THS in real-life setting

Active Comparator: SA
Former cigarette smokers with minimum of 2 years of smoking abstinence
Other: Smoking abstinence
Subjects (former cigarette smokers) will continue smoking abstinence (confirmed by cotinine test, with a threshold of < 100 ng/mL)




Primary Outcome Measures :
  1. Carboxyhemoglobin (COHb) in blood [ Time Frame: Measured when subject visits study site on day 1. ]
    Carboxyhemoglobin (COHb) is assayed from whole blood. Expressed as % of saturation of hemoglobin. Geometric Mean values are provided as descriptive statistics.

  2. Total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (total NNAL) in urine [ Time Frame: Measured when subject visits study site on day 1. ]
    Concentrations measured in urine and expressed as concentration adjusted for creatinine (pg/mg creat). Geometric Mean values are provided as descriptive statistics.

  3. White Blood Cell total count (WBC) in blood [ Time Frame: Measured when subject visits study site on day 1. ]
    Total count in blood (GI/L). Mean values are provided as descriptive statistics.

  4. 8-epi-Prostaglandin-F2α (8-epi-PGF2α) in urine [ Time Frame: Measured when subject visits study site on day 1. ]
    Concentrations measured in urine and expressed as concentration adjusted for creatinine (pg/mg creat). Geometric Mean values are provided as descriptive statistics.


Secondary Outcome Measures :
  1. High-Density Lipoprotein Cholesterol (HDL-C) [ Time Frame: Measured when subject visits study site on day 1. ]
    Concentrations (mg/dL) measured in serum. Mean values are provided as descriptive statistics.

  2. soluble Intercellular Adhesion Molecule-1 (sICAM-1) [ Time Frame: Measured when subject visits study site on day 1. ]
    Concentrations (ng/mL) measured in serum. Geometric Mean values are provided as descriptive statistics.

  3. 11-dehydrothromboxane B2 (11-DTX-B2) [ Time Frame: Measured when subject visits study site on day 1. ]
    Concentrations measured in urine and expressed as concentration adjusted for creatinine (pg/mg creat). Geometric Mean values are provided as descriptive statistics.

  4. Augmentation Index (AIx) [ Time Frame: Measured when subject visits study site on day 1. ]
    The augmentation index (AIx) is a measure of systemic arterial stiffness, and is defined as the ratio of augmentation (Δ P) to central pulse pressure and expressed as percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure.

  5. Forced Expiratory Volume in 1 second (FEV1) %predicted, post-bronchodilator (post-BD) [ Time Frame: Measured when subject visits study site on day 1. ]
    FEV1 post-bronchodilator and expressed as percentage predicted (FEV1 %pred). Mean values are provided as descriptive statistics.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   30 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05385055


Contacts
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Contact: Christelle Haziza, PhD +41 58 242 11 11 Christelle.Haziza@pmi.com
Contact: S. Michael Ansari +41 58 242 11 11

Locations
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Czechia
Clintrial s.r.o. Recruiting
Praha, Czechia
Contact       r.gregar@clintrial.cz   
Principal Investigator: Roman Gregar, MD         
Vestra Clinics s.r.o. Recruiting
Rychnov nad Kněžnou, Czechia
Contact       pazdera@vestraclinics.org   
Principal Investigator: Ladislav Pazdera, MD         
Germany
emovis GmbH Recruiting
Berlin, Germany
Contact       Luci.Magimaiseelan@emovis.de   
Principal Investigator: Luci Magimaiseelan, MD         
Sibamed GmbH & Co.KG Recruiting
Leipzig, Germany
Contact       helena@sigal-sms.de   
Principal Investigator: Helena Sigal, MD         
Centrum für Diagnostik und Gesundheit, Klinische Forschung und Entwicklung Recruiting
München, Germany
Contact       manfred.hartard@sigal-sms.de   
Principal Investigator: Manfred Hartard, MD         
Praxis Reinfeld Mitte Recruiting
Reinfeld, Germany
Contact       joachim.weimer@sigal-sms.de   
Principal Investigator: Joachim Weimer, MD         
Hautarzt Stuttgart - Hautarztpraxis Leitz & Kollegen Recruiting
Stuttgart, Germany
Contact       Nicolas.leitz@sigal-sms.de   
Principal Investigator: Nicolas Leitz, MD         
Greece
Hygeia Hospital Recruiting
Athens, Greece
Contact       cardio@tsougos.gr   
Principal Investigator: Elias Tsougos, MD         
National and Kapodistrian University of Athens, Medical school, Attikon Hospital, 2nd Cardiology Department Recruiting
Athens, Greece
Principal Investigator: Ignatios Ikonomidis, MD         
Japan
Hakata Clinic Recruiting
Fukuoka, Japan
Contact       Takashi-eto@lta-med.com   
Principal Investigator: Takashi Etou, MD         
Nishikumamoto Hospital Recruiting
Minami, Japan
Contact       takanori-tanaka@lta-med.com   
Principal Investigator: Takanori Tanaka, MD         
Sumida Hospital Recruiting
Tokyo, Japan
Contact       takuma-yonemura@lta-med.com   
Principal Investigator: Takuma Yonemura, MD         
Sponsors and Collaborators
Philip Morris Products S.A.
Investigators
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Study Chair: Christelle Haziza, PhD Philip Morris Products S.A.
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Responsible Party: Philip Morris Products S.A.
ClinicalTrials.gov Identifier: NCT05385055    
Other Study ID Numbers: P1-RMC-03-INT
First Posted: May 23, 2022    Key Record Dates
Last Update Posted: July 13, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Inflammation
Pathologic Processes