The ESTxENDS Trial- Substudy on the Metabolic Effects of Using Electronic Nicotine Delivery Systems (ENDS/Vaporizer/E-cig)

Study Overview
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Brief Summary
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--> This is a substudy of the main ESTxENDS trial (NCT03589989). Metabolic outcomes should be considered secondary outcomes of the main smoking cessation outcome formulated in NCT03589989. Cardiovascular diseases (CVD) are a leading cause of death in cigarette smokers; quitting smoking is associated with reduced CVD. Cigarette smoking increases CVD through complex mechanisms, mostly on an increase in atherosclerosis and the effect appears unrelated to nicotine. Recently, electronic nicotine delivery systems (ENDS; also called vaporizer or electronic cigarette) have become popular with smokers who want to stop smoking. There is currently no evidence that ENDS use affects CVD outcomes. The nicotine contained in the e-liquids from ENDS has cardiovascular effects and the evidence about health effects mostly comes from studies on nicotine replacement therapy (NRT). These studies did not show an increased risk of CVD from NRTs. The ECLAT trial showed no difference in body weight, resting heart rate, or blood pressure between those who used ENDS or not. Two studies evaluated the short-term effects of ENDS on the cardiovascular system. One study suggested impairment in diastolic ventricular function with cigarettes and not with ENDS. Both ENDS and cigarettes increased diastolic blood pressure, potentially mediated through nicotine exposure, but an increased systolic blood pressure was found only in cigarette smokers. Other studies have suggested no changes in blood pressure in daily users of electronic cigarettes up to 1 year with some even a reduction in blood pressure among patients with hypertension. Interventions helping smokers quit have shown that quitting is associated with increased HDL-cholesterol, weight gain, higher blood glucose, and higher diabetes risk. No large randomized trials have tested the effect of ENDS on blood cholesterol and other markers of cardiovascular risk. This study will therefore test the efficacy of ENDS for cigarette smoking cessation, the safety of ENDS on adverse events and the effect of ENDS on health-related outcomes and exposure to inhaled chemicals. For the main ESTxENDS trial (NCT03589989), smokers motivated to quit smoking cigarettes will be included. Participants in the intervention group will receive an ENDS and nicotine-containing e-liquids, which they will be allowed to use ad libitum. Additionally, they will receive smoking cessation counseling. Participants in the control group will receive smoking cessation counseling only. All participants will be followed over a 24-month period. Measurements of risk factors for cardiovascular diseases will be done at baseline and at 6, 12 and 24 months' follow-up.

Official Title
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Substudy of Efficacy, Safety and Toxicology of Electronic Nicotine Delivery Systems as an Aid for Smoking Cessation (ESTxENDS Trial)- the Metabolic Substudy of ESTxENDS

Conditions
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Smoking Cessation, Cardiovascular Diseases

Intervention / Treatment
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* Other: ENDS (vaporizer/e-cig) and smoking cessation counseling
* Other: Smoking cessation counseling


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Informed Consent as documented by signature Persons aged 18 or older Currently smoking 5 or more cigarettes a day for at least 12 months Willing to try to quit smoking within the next 3 months, Persons providing a valid phone number, a valid email address and/or a valid postal address. Exclusion criteria: Known hypersensitivity or allergy to contents of the e-liquid Participation in another study with investigational drug within the 30 days preceding the baseline visit and during the present study where interactions are to be expected Women who are pregnant or breast feeding Intention to become pregnant during the course of the scheduled study intervention, i.e. within the first 6-months of the study Persons having used ENDS or tobacco heating systems regularly in the 3 months preceding the baseline visit Persons having used nicotine replacement therapy (NRT) or other medications with demonstrated efficacy as an aid for smoking cessation such as varenicline or bupropion within the 3 months preceding the baseline visit Persons who cannot attend the 6- month follow-up visit for any reason Cannot understand instructions delivered in person or by phone, or otherwise unable to participate in study procedures

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br> | Other: ENDS (vaporizer/e-cig) and smoking cessation counseling<br>* Participants in the intervention group will receive an ENDS and nicotine-containing e-liquids, which they will be allowed to use ad libitum. Additionally, they will receive smoking cessation counseling. Participants will be allowed to additionally use nicotine replacement therapy. All participants will be followed over a 24-month period. Smoking cessation counseling will be provided in person at the first clinical visit and then over the phone at the target quit date one week later and again at week 2, 4 and 8 after the target quit date. After 6, 12 and 24 months, participants will be asked to come to a clinical visit.<br>|
| Active Comparator: Control group<br> | Other: Smoking cessation counseling<br>* Participants in the control group will receive smoking cessation counseling only. Participants will be allowed to additionally use nicotine replacement therapy. All participants will be followed over a 24-month period. Smoking cessation counseling will be provided in person at the first clinical visit and then over the phone at the target quit date one week later and again at week 2, 4 and 8 after the target quit date. After 6, 12 and 24 months, participants will be asked to come to a clinical visit.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurements of risk factors for cardiovascular diseases (blood pressure)_1 | Measurement of blood pressure | 6 months post quit date | 
| Measurements of risk factors for cardiovascular diseases (blood pressure)_2 | Measurement of blood pressure | 12 months post quit date | 
| Measurements of risk factors for cardiovascular diseases (blood pressure)_3 | Measurement of blood pressure | 24 months post quit date | 
| Measurements of risk factors for cardiovascular diseases (heart rate)_1 | Measurement of heart rate | 6 months post quit date | 
| Measurements of risk factors for cardiovascular diseases (heart rate)_2 | Measurement of heart rate | 12 months post quit date | 
| Measurements of risk factors for cardiovascular diseases (heart rate)_3 | Measurement of heart rate | 24 months post quit date | 
| Measurements of risk factors for cardiovascular diseases (total cholesterol)_1 | Measurement of total cholesterol | 6 months post quit date | 
| Measurements of risk factors for cardiovascular diseases (total cholesterol)_2 | Measurement of total cholesterol | 12 months post quit date | 
| Measurements of risk factors for cardiovascular diseases (total cholesterol)_3 | Measurement of total cholesterol | 24 months post quit date | 
| Measurements of risk factors for cardiovascular diseases (LDL-cholesterol)_1 | Measurement of LDL-cholesterol | 6 months post quit date | 
| Measurements of risk factors for cardiovascular diseases (LDL-cholesterol)_2 | Measurement of LDL-cholesterol | 12 months post quit date | 
| Measurements of risk factors for cardiovascular diseases (LDL-cholesterol)_3 | Measurement of LDL-cholesterol | 24 months post quit date | 
| Measurements of risk factors for cardiovascular diseases (HDL-cholesterol)_1 | Measurement of HDL-cholesterol | 6 months post quit date | 
| Measurements of risk factors for cardiovascular diseases (HDL-cholesterol)_2 | Measurement of HDL-cholesterol | 12 months post quit date | 
| Measurements of risk factors for cardiovascular diseases (HDL-cholesterol)_3 | Measurement of HDL-cholesterol | 24 months post quit date | 
| Measurements of risk factors for cardiovascular diseases (triglycerides)_1 | Measurement of triglycerides | 6 months post quit date | 
| Measurements of risk factors for cardiovascular diseases (triglycerides)_2 | Measurement of triglycerides | 12 months post quit date | 
| Measurements of risk factors for cardiovascular diseases (triglycerides)_3 | Measurement of triglycerides | 24 months post quit date | 
| Measurements of risk factors for cardiovascular diseases (HbA1c)_1 | Measurement of HbA1c for persons with diagnosed diabetes | 6 months post quit date | 
| Measurements of risk factors for cardiovascular diseases (HbA1c)_2 | Measurement of HbA1c for persons with diagnosed diabetes | 12 months post quit date | 
| Measurements of risk factors for cardiovascular diseases (HbA1c)_3 | Measurement of HbA1c for persons with diagnosed diabetes | 24 months post quit date | 
| Measurements of risk factors for cardiovascular diseases (creatinine)_1 | Measurement of creatinine | 6 months post quit date | 
| Measurements of risk factors for cardiovascular diseases (creatinine)_2 | Measurement of creatinine | 12 months post quit date | 
| Measurements of risk factors for cardiovascular diseases (creatinine)_3 | Measurement of creatinine | 24 months post quit date | 
| Measurements of risk factors for cardiovascular diseases (waist circumference)_1 | Measurement of waist circumference | 6 months post quit date | 
| Measurements of risk factors for cardiovascular diseases (waist circumference)_2 | Measurement of waist circumference | 12 months post quit date | 
| Measurements of risk factors for cardiovascular diseases (waist circumference)_3 | Measurement of waist circumference | 24 months post quit date | 
| Measurements of risk factors for cardiovascular diseases (body mass index, BMI)_1 | Measurements of weight and height to report BMI in kg/m^2 | 6 months post quit date | 
| Measurements of risk factors for cardiovascular diseases (body mass index, BMI)_2 | Measurements of weight and height to report BMI in kg/m^2 | 12 months post quit date | 
| Measurements of risk factors for cardiovascular diseases (body mass index, BMI)_3 | Measurements of weight and height to report BMI in kg/m^2 | 24 months post quit date | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in cardiovascular disease risk factors (blood pressure) | Measurement of blood pressure | Change from Baseline to 6,12, 24 months post quit date | 
| Changes in cardiovascular disease risk factors (heart rate) | Measurement of heart rate | Change from Baseline to 6,12, 24 months post quit date | 
| Changes in cardiovascular disease risk factors (total cholesterol) | Measurement of total cholesterol | Change from Baseline to 6,12, 24 months post quit date | 
| Changes in cardiovascular disease risk factors (LDL-cholesterol) | Measurement of LDL-cholesterol | Change from Baseline to 6,12, 24 months post quit date | 
| Changes in cardiovascular disease risk factors (HDL- cholesterol) | Measurement of HDL- cholesterol | Change from Baseline to 6,12, 24 months post quit date | 
| Changes in cardiovascular disease risk factors (triglycerides) | Measurement of triglycerides | Change from Baseline to 6,12, 24 months post quit date | 
| Changes in cardiovascular disease risk factors (HbA1c) | Measurement of HbA1c for persons with diagnosed diabetes | Change from Baseline to 6,12, 24 months post quit date | 
| Changes in cardiovascular disease risk factors (creatinine) | Measurement of creatinine | Change from Baseline to 6,12, 24 months post quit date | 
| Changes in cardiovascular disease risk factors (waist circumference) | Measurement of waist circumference | Change from Baseline to 6,12, 24 months post quit date | 
| Changes in cardiovascular disease risk factors (body mass index, BMI) | Measurements of weight and height to report BMI in kg/m^2 | Change from Baseline to 6,12, 24 months post quit date | 
| Physical activity | Measured using the International Physical activity questionnaire (IPAQ). The short version (7 items) provides information on the time spent walking, in vigorous- and moderate-intensity activity and in sedentary activity. | 6,12, 24 months post quit date | 
| Changes of physical activity | Measured using the International Physical activity questionnaire (IPAQ). The short version (7 items) provides information on the time spent walking, in vigorous- and moderate-intensity activity and in sedentary activity. | Change from Baseline to 6,12, 24 months post quit date |