Effect of Switching From Cigarette Smoking to IQOS on Exercise Capacity

• ClinicalTrials.gov Identifier: NCT03887117
• Recruitment Status: Completed
• First Posted: March 22, 2019
• Results First Posted: December 27, 2021
• Last Update Posted: December 27, 2021
• Sponsor: Philip Morris Products S.A.
• Information provided by (Responsible Party): Philip Morris Products S.A.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Smoking; Exercise Capacity	Other: IQOS + Exercise Training Program; Other: IQOS without Exercise Training Program; Other: Cigarette Smoking + Exercise Training Program; Other: Smoking Abstinence + Exercise Training Program	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 94 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• 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
• Actual Study Start Date: February 1, 2019
• Actual Primary Completion Date: November 25, 2019
• Actual Study Completion Date: March 16, 2020

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: IQOS-1; IQOS + Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use and participate in an exercise training program.	Other: IQOS + Exercise Training Program; Switch to IQOS use + participation in a training program
Active Comparator: IQOS-2; IQOS without Exercise Training Program Subjects randomized to IQOS use will switch to IQOS use, but will not participate in an exercise training program.	Other: IQOS without Exercise Training Program; Switch to IQOS use only, without participation in a training program
Active Comparator: Cigarette Smoking; Cigarette Smoking + Exercise Training Program Subjects randomized to continued cigarette smoking and participation in an exercise training program.	Other: Cigarette Smoking + Exercise Training Program; Continue to smoke cigarettes + participation in a training program
Active Comparator: Smoking Abstinence; Smoking Abstinence + Exercise Training Program Subjects randomized to smoking abstinence and participation in an exercise training program.	Other: Smoking Abstinence + Exercise Training Program; Switch to smoking abstinence + participation in a training program

Outcome Measures

Primary Outcome Measures :

1. Maximal Oxygen Uptake (VO2max, Absolute Values) [ Time Frame: Measured at baseline (V3), at week 1 (V4), and at week 12 (V43). ]
   To measure VO2max during maximal cycle ergometer exercise (expressed in absolute values [mL*min-1]).
2. Maximal Oxygen Uptake (VO2max, Weight-adjusted Values) [ Time Frame: Measured at baseline (V3), at week 1 (V4), and at week 12 (V43). ]
   To measure VO2max during maximal cycle ergometer exercise (expressed in weight-adjusted [mL*kg-1*min-1] values).
3. Maximal Oxygen Uptake (VO2max, Fat-free Weight Adjusted Values) [ Time Frame: Measured at baseline (V3), at week 1 (V4), and at week 12 (V43). ]
   To measure VO2max during maximal cycle ergometer exercise (expressed in fat-free weight adjusted values [mL*kg-1*min-1]).
4. Exercise Capacity [ Time Frame: Measured at baseline (V3), at week 1 (V4), and at week 12 (V43) ]
   To measure exercise capacity, by measuring time to complete a pre-defined work (determined as 25% more work than the study subject produced during baseline VO2max test) on a cycle ergometer (seconds).
5. Exercise Training Intensity: Cumulative Work [ Time Frame: Measured during 38 exercise training sessions of 40 minutes duration, conducted approximately 3 times a week, over 12 weeks. ]
   To measure cumulative work (calories) produced during each 40 minute exercise training session, performed on a stationary bike, over 12 weeks.
6. Exercise Training Intensity: Average Work Rate [ Time Frame: Measured during 38 exercise training sessions of 40 minutes duration, conducted approximately 3 times a week, over 12 weeks. ]
   To measure the average work rate (watt) during each 40 minute exercise training session, performed on a stationary bike, over 12 weeks.
7. Exercise Training Intensity: Average Heart Rate [ Time Frame: Measured during 38 exercise training sessions of 40 minutes duration, conducted approximately 3 times a week, over 12 weeks. ]
   To measure the average heart rate (bpm) during each 40 minute exercise training session, performed on a stationary bike, over 12 weeks.
8. Exercise Training Intensity: Time Spent at Maximal Heart Rate [ Time Frame: Measured during 38 exercise training sessions of 40 minutes duration, conducted approximately 3 times a week, over 12 weeks. ]
   To measure the time (seconds) spent at 0-50%, 50-60%, 60-70%, 70-80 % and >80% of maximal heart rate during each 40 minute exercise training session, performed on a stationary bike, over 12 weeks.
9. Hemoglobin Mass [ Time Frame: Measured at Baseline (V3) and week 12 (V43). ]
   To measure Hemoglobin mass (g), measured with the carbon monoxide-rebreathing method.
10. Red Blood Cell Volume [ Time Frame: Measured at Baseline (V3) and week 12 (V43). ]
    To measure Red blood cell volume (mL), measured with the carbon monoxide-rebreathing method.
11. Plasma Volume [ Time Frame: Measured at Baseline (V3) and week 12 (V43). ]
    To measure Plasma volume (mL), measured with the carbon monoxide-rebreathing method.
12. Total Blood Volume [ Time Frame: Measured at Baseline (V3) and week 12 (V43). ]
    To measure total blood volume (mL), measured with the carbon monoxide-rebreathing method.
13. Capillary Blood Lactate Levels [ Time Frame: Measured at Baseline and week 15. ]
    To measure changes from baseline of Capillary blood lactate levels (mmol/L), measured (with a portable lactate analyzer) during VO2max test.
14. Ventilation at VO2 Max [ Time Frame: Measured at Baseline (V3), at week 1 (V4), and at week 12 (V43). ]
    To measure ventilation (L/min) at VO2max.
15. Respiratory Rate [ Time Frame: Measured at Baseline (V3), at week 1 (V4), and at week 12 (V43). ]
    To measure respiratory rate (breaths per minute) at VO2max.
16. VCO2 [ Time Frame: Measured at Baseline (V3), at week 1 (V4), and at week 12 (V43). ]
    To measure VCO2 (L/min) at VO2 max.
17. Respiratory Exchange Ratio [ Time Frame: Measured at Baseline (V3), at week 1 (V4), and at week 12 (V43). ]
    To measure the respiratory exchange ratio (VCO2/VO2) at VO2max
18. Rating of Perceived Capacity by Sex [ Time Frame: Measured at Baseline (V3), at week 1 (V4), and at week 12 (V43). ]
    To measure Rating of Perceived Capacity (RPC), determined by using the RPC scale. The RPC scale is a list of physical activities arranged in order, with a scale of values from least strenuous (1) to most exhausting (18 for women, 20 for men). Subjects choose the most strenuous activity, with corresponding value, which they could sustain for 30 minutes.
19. Rating of Perceived Exertion [ Time Frame: Measured at Baseline (V3), at week 1 (V4), and at week 12 (V43). ]
    To measure changes from baseline of the Rating of Perceived Exertion, determined by using the Borg scale. The Borg RPE scale is a numerical scale that ranges from 6 to 20, where 6 means "no exertion at all" and 20 means "maximal exertion." Subjects choose a number from the scale that best describes their level of exertion during a physical activity.
20. Heart Rate [ Time Frame: Measured at Baseline, at week 1, and at week 15. ]
    To measure changes from baseline of heart rate (bpm) during VO2max test.
21. Oxygen Uptake [ Time Frame: Measured at Baseline, at week 1, and at week 15. ]
    To measure changes from baseline of Oxygen uptake during VO2max test. (mL/min)
22. High Density Lipoprotein (HDL) [ Time Frame: Measured at Baseline (V3), week 6 (V14), week 10 (V28), and week 12 (V43). ]
    To measure HDL concentrations in serum (mg/dL).
23. Low Density Lipoprotein (LDL) [ Time Frame: Measured at Baseline (V3), week 6 (V14), week 10 (V28), and week 12 (V43). ]
    To measure LDL concentrations in serum (mg/dL).
24. Very Low Density Lipoprotein (VLDL) [ Time Frame: Measured at Baseline (V3), week 6 (V14), week 10 (V28), and week 12 (V43). ]
    To measure VLDL concentrations in serum (mg/dL).
25. High Sensitivity C-reactive Protein (Hs-CRP) [ Time Frame: Measured at Baseline (V3), week 6 (V14), week 10 (V28), and week 12 (V43). ]
    To measure hs-CRP concentrations in serum (mg/dL).
26. Growth Hormone [ Time Frame: Measured at Baseline (V3), week 6 (V14), week 10 (V28), and week 12 (V43). ]
    To measure growth hormone concentrations in serum (ng/mL).
27. Hemoglobin A1c (HbA1c) [ Time Frame: Measured at Baseline (V3), week 6 (V14), week 10 (V28), and week 12 (V43). ]
    To measure glycosylated hemoglobin (HbA1c in whole blood).
28. Resting Systolic Blood Pressure [ Time Frame: Measured at Baseline (V3), week 6 (V14), week 10 (V28), and week 12 (V43). ]
    To measure resting systolic blood pressure in mmHg.
29. Resting Pulse Rate [ Time Frame: Measured at Baseline (V3), week 6 (V14), week 10 (V28), and week 12 (V43). ]
    To measure resting heart rate in bpm.
30. Body Fat [ Time Frame: Measured at Baseline (V3), at week 1 (V4), and at week 12 (V43). ]
    To measure body fat as a percentage.
31. Waist Circumference [ Time Frame: Measured at Baseline (V3), at week 1 (V4), and at week 12 (V43). ]
    To measure waist circumference in cm.
32. Body Weight [ Time Frame: Measured at each visit, starting from Baseline (V3) until week 12 (V43). ]
    To measure body weight in kilograms.
33. Exhaled Carbon Monoxide [ Time Frame: Measured at each visit, starting from Baseline (V3) until week 12 (V43). ]
    To measure exhaled carbon monoxide (ppm).
34. Carboxyhemoglobin [ Time Frame: Measured at Baseline (V3), week 1 (V4), week 6 (V14), week 10 (V28), and week 12 (V43). ]
    To measure Carboxyhemoglobin (COHb), assayed from whole blood. Expressed as % of saturation of hemoglobin.
35. NEQ [ Time Frame: Measured at Baseline (V3), week 1 (V4), week 6 (V14), week 10 (V28), and week 12 (V43). ]
    To measure Nicotine equivalents (NEQ) concentrations, measured in spot urine and expressed as concentration adjusted for creatinine.
36. Total NNAL [ Time Frame: Measured at Baseline (V3), week 1 (V4), week 6 (V14), week 10 (V28), and week 12 (V43). ]
    To measure Total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) concentrations, measured in spot urine and expressed as concentration adjusted for creatinine.
37. CEMA [ Time Frame: Measured at Baseline (V3), week 1 (V4), week 6 (V14), week 10 (V28), and week 12 (V43). ]
    To measure 2-cyanoethylmercapturic acid (CEMA) concentrations, measured in spot urine and expressed as concentration adjusted for creatinine.
38. Nicotine/Tobacco Product Use (Cigarettes) [ Time Frame: Recorded daily by subject, in product use diary, from study enrollment for 16 weeks. ]
    To measure self-reported number of any nicotine/tobacco product used on a daily basis.
39. Nicotine/Tobacco Product Use (HeatSticks) [ Time Frame: Recorded daily by subject, in product use diary, from study enrollment for 16 weeks. ]
    To measure self-reported number of any nicotine/tobacco product used on a daily basis.
40. Nicotine/Tobacco Product Use (E-cigarettes) [ Time Frame: Recorded daily by subject, in product use diary, from study enrollment for 16 weeks. ]
    To measure self-reported number of any nicotine/tobacco product used on a daily basis.

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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).

Contacts and Locations

Locations

Germany

CRS Clinical Research Services Mannheim GmbH

Mannheim, Germany, D-68167

Sponsors and Collaborators

Philip Morris Products S.A.

Investigators

• Principal Investigator: Armin Schultz, MD; CRS Clinical Research Services Mannheim GmbH
• Study Chair: Christelle Haziza, PhD; Philip Morris Products S.A.

  Study Documents (Full-Text)

Documents provided by Philip Morris Products S.A.:

Study Protocol  [PDF] May 2, 2019

Statistical Analysis Plan  [PDF] March 10, 2020

More Information

• Responsible Party: Philip Morris Products S.A.
• ClinicalTrials.gov Identifier: NCT03887117
• Other Study ID Numbers: P1-EXC-01-EU
• First Posted: March 22, 2019
• Results First Posted: December 27, 2021
• Last Update Posted: December 27, 2021
• Last Verified: November 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Philip Morris Products S.A.:

IQOS; Heated Tobacco