Clinical trial NCT03887117: Effect of Switching From Cigarette Smoking to IQOS on Exercise Capacity
Official title: A Randomized, Controlled, Open-label, 4-arm Parallel Group Study to Evaluate the Effect of Switching From Cigarette Smoking to the Use of IQOS in Healthy Adult Current Smokers on Exercise Capacity and Trainability
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Smoking
Exercise Capacity
Keywords: IQOS
Heated Tobacco
Lead sponsor: Philip Morris Products S.A.
Sponsor class: INDUSTRY
First posted: 2019-03-22
Enrollment: 94
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This exploratory study is part of the global clinical assessment program of IQOS. It was designed to provide scientific evidence to further substantiate the reduced risk potential of using a heated tobacco product (the Tobacco Heating System \[THS\] marketed as IQOS) as compared to smoking cigarettes. The main goals of this exploratory study were to assess whether switching from cigarette smoking to using IQOS would influence 1) maximum oxygen uptake during incremental exercise (VO2max) and exercise capacity, 2) ability to perform exercise training and thereby influence 3) VO2max after 12 weeks of exercise training, 4) physiological parameters and biological health markers, and finally 5) physical activity levels in daily life.

Detailed description: This exploratory study, with healthy adult smokers, was designed without product use restrictions (ad libitum product use) in order to replicate as closely as possible "real life" conditions. Subjects randomized to the cigarette and IQOS arms were asked to buy their own cigarettes or HeatSticks, respectively. Subjects randomized to the smoking abstinence (SA) arm were instructed to stay smoking abstinent until the end of the study. Subjects in the SA arm received smoking abstinence support and, in order to prevent relapse to cigarette smoking during the training program, were also allowed to use nicotine replacement therapy.

Mobile health technology was used in the study to explore the impact on switching from smoking to using IQOS on physical activity in daily real-world living conditions. The wearable enabled non-invasive recording of physical activity in an objective manner throughout the study. However, results collected from this device will be reported separately.

It should be noted that some study outcomes were reported graphically, rather than numerically. Consequently, these outcomes have not been included in this results disclosure.

Eligibility criteria: Inclusion Criteria:

* Smoking, healthy subject based on safety laboratory, ECG, spirometry, vital signs, physical examination, medical history and Investigator's assessment.
* Subject has been smoking for at least three years prior to V1.
* Subject has been smoking ≥ 10 cigarettes per day over the last 12 months. Smoking status will be verified by a urinary cotinine ≥ 200 ng/mL and CO exhaled breath test \> 10 ppm both at V1 and V2.
* Subject does not plan to quit smoking within 6 months after V1.

Exclusion Criteria:

* Subject has a clinically relevant disease which requires medication (including but not limited to gastrointestinal, renal, hepatic, neurological, hematological, endocrine, oncological, urological, immunological, pulmonary \[such as but not limited to pulmonary oedema, asthma\], and cardiovascular \[such as, but not limited to myocardial infarction, unstable angina, uncontrolled arrhythmias, heart failure\], disease) or any other clinically significant medical condition (including abnormal safety laboratory result as per CTCAE), which as per the judgment of the Investigator would jeopardize the safety of the subject.
* Subject performs more than 45 min of vigorous physical activity per week.
* Subject takes medication influencing blood volume such as erythropoietin, diuretics and beta blockers, or diabetic medications.
* Subject cannot participate in the study for any reason other than medical as per the Investigator's judgment (e.g. psychological and/or social reason)
* For women only: subject is pregnant (does not have negative pregnancy tests at V1 and at V2) or is breastfeeding.
* For women of childbearing potential : female subject who does not agree to using an acceptable method of effective contraception during the entire study.
* Subject has a BMI \< 18.5 kg/m2 or BMI ≥ 30 kg/m2.
* Subject has a positive urine drug screen.
* Subject has been previously screened for this study.
* Subject, or one of their family members (e.g., spouse, parent, sibling or child), is a current or former employee of the tobacco industry.
* Subject, or one of their family members (e.g. spouse, parent, sibling or child), is an employee of the investigational site or any other parties involved in the study.
* Subject is legally incompetent, or physically or mentally incapable of giving consent (e.g., emergency situation, under guardianship, prisoners, or subjects who are involuntarily incarcerated).

Primary outcomes:
measure: Maximal Oxygen Uptake (VO2max, Absolute Values)
timeFrame: Measured at baseline (V3), at week 1 (V4), and at week 12 (V43).
measure: Maximal Oxygen Uptake (VO2max, Weight-adjusted Values)
timeFrame: Measured at baseline (V3), at week 1 (V4), and at week 12 (V43).
measure: Maximal Oxygen Uptake (VO2max, Fat-free Weight Adjusted Values)
timeFrame: Measured at baseline (V3), at week 1 (V4), and at week 12 (V43).
measure: Exercise Capacity
timeFrame: Measured at baseline (V3), at week 1 (V4), and at week 12 (V43)
measure: Exercise Training Intensity: Cumulative Work
timeFrame: Measured during 38 exercise training sessions of 40 minutes duration, conducted approximately 3 times a week, over 12 weeks.
measure: Exercise Training Intensity: Average Work Rate
timeFrame: Measured during 38 exercise training sessions of 40 minutes duration, conducted approximately 3 times a week, over 12 weeks.
measure: Exercise Training Intensity: Average Heart Rate
timeFrame: Measured during 38 exercise training sessions of 40 minutes duration, conducted approximately 3 times a week, over 12 weeks.
measure: Exercise Training Intensity: Time Spent at Maximal Heart Rate
timeFrame: Measured during 38 exercise training sessions of 40 minutes duration, conducted approximately 3 times a week, over 12 weeks.
measure: Hemoglobin Mass
timeFrame: Measured at Baseline (V3) and week 12 (V43).
measure: Red Blood Cell Volume
timeFrame: Measured at Baseline (V3) and week 12 (V43).
measure: Plasma Volume
timeFrame: Measured at Baseline (V3) and week 12 (V43).
measure: Total Blood Volume
timeFrame: Measured at Baseline (V3) and week 12 (V43).
measure: Capillary Blood Lactate Levels
timeFrame: Measured at Baseline and week 15.
measure: Ventilation at VO2 Max
timeFrame: Measured at Baseline (V3), at week 1 (V4), and at week 12 (V43).
measure: Respiratory Rate
timeFrame: Measured at Baseline (V3), at week 1 (V4), and at week 12 (V43).
measure: VCO2
timeFrame: Measured at Baseline (V3), at week 1 (V4), and at week 12 (V43).
measure: Respiratory Exchange Ratio
timeFrame: Measured at Baseline (V3), at week 1 (V4), and at week 12 (V43).
measure: Rating of Perceived Capacity by Sex
timeFrame: Measured at Baseline (V3), at week 1 (V4), and at week 12 (V43).
measure: Rating of Perceived Exertion
timeFrame: Measured at Baseline (V3), at week 1 (V4), and at week 12 (V43).
measure: Heart Rate
timeFrame: Measured at Baseline, at week 1, and at week 15.
measure: Oxygen Uptake
timeFrame: Measured at Baseline, at week 1, and at week 15.
measure: High Density Lipoprotein (HDL)
timeFrame: Measured at Baseline (V3), week 6 (V14), week 10 (V28), and week 12 (V43).
measure: Low Density Lipoprotein (LDL)
timeFrame: Measured at Baseline (V3), week 6 (V14), week 10 (V28), and week 12 (V43).
measure: Very Low Density Lipoprotein (VLDL)
timeFrame: Measured at Baseline (V3), week 6 (V14), week 10 (V28), and week 12 (V43).
measure: High Sensitivity C-reactive Protein (Hs-CRP)
timeFrame: Measured at Baseline (V3), week 6 (V14), week 10 (V28), and week 12 (V43).
measure: Growth Hormone
timeFrame: Measured at Baseline (V3), week 6 (V14), week 10 (V28), and week 12 (V43).
measure: Hemoglobin A1c (HbA1c)
timeFrame: Measured at Baseline (V3), week 6 (V14), week 10 (V28), and week 12 (V43).
measure: Resting Systolic Blood Pressure
timeFrame: Measured at Baseline (V3), week 6 (V14), week 10 (V28), and week 12 (V43).
measure: Resting Pulse Rate
timeFrame: Measured at Baseline (V3), week 6 (V14), week 10 (V28), and week 12 (V43).
measure: Body Fat
timeFrame: Measured at Baseline (V3), at week 1 (V4), and at week 12 (V43).
measure: Waist Circumference
timeFrame: Measured at Baseline (V3), at week 1 (V4), and at week 12 (V43).
measure: Body Weight
timeFrame: Measured at each visit, starting from Baseline (V3) until week 12 (V43).
measure: Exhaled Carbon Monoxide
timeFrame: Measured at each visit, starting from Baseline (V3) until week 12 (V43).
measure: Carboxyhemoglobin
timeFrame: Measured at Baseline (V3), week 1 (V4), week 6 (V14), week 10 (V28), and week 12 (V43).
measure: NEQ
timeFrame: Measured at Baseline (V3), week 1 (V4), week 6 (V14), week 10 (V28), and week 12 (V43).
measure: Total NNAL
timeFrame: Measured at Baseline (V3), week 1 (V4), week 6 (V14), week 10 (V28), and week 12 (V43).
measure: CEMA
timeFrame: Measured at Baseline (V3), week 1 (V4), week 6 (V14), week 10 (V28), and week 12 (V43).
measure: Nicotine/Tobacco Product Use (Cigarettes)
timeFrame: Recorded daily by subject, in product use diary, from study enrollment for 16 weeks.
measure: Nicotine/Tobacco Product Use (HeatSticks)
timeFrame: Recorded daily by subject, in product use diary, from study enrollment for 16 weeks.
measure: Nicotine/Tobacco Product Use (E-cigarettes)
timeFrame: Recorded daily by subject, in product use diary, from study enrollment for 16 weeks.
Secondary outcomes:
Other outcomes:
Locations:
city: Mannheim
country: Germany
facility: CRS Clinical Research Services Mannheim GmbH
Study officials:
affiliation: CRS Clinical Research Services Mannheim GmbH
name: Armin Schultz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Philip Morris Products S.A.
name: Christelle Haziza, PhD
role: STUDY_CHAIR
References: