Pharmacokinetic Profile of Toxic Substances and Nicotine in Electronic Cigarettes

Study Overview
=================
Brief Summary
-----------------
The aim of the present study is to compare serum nicotine levels of different e-Cigarette strength with usual cigarettes. Serum levels of carcinogenic and toxic substances will be also compared.

Detailed Description
-----------------
The study is randomised cross-over trial designed to compare: 1) serum nicotine levels of four different e-Cigarette strength ; 2) Serum levels of carcinogenic and toxic substances will be also compared. Participants will be requested to abstain from smoking and alcohol from 20:00 on the night before each study day and from food and caffeine for at least 1 h before the session. On arrival at the study centre, carbon monoxide (CO) will be measured in participants' expired breath. If CO will be less than 15 parts per million (ppm), the assigned study treatment will be allocated; however, if CO was > 15 ppm or they will report smoking in the previous 12 h, participants will be rescheduled wherever possible to a subsequent session. On the first study day, participants will be randomised to use one of five ordered conditions (each separated by 3 day): ENDDs (fourth generation) containing nicotine 2,4%; ENDDs (second generation) containing nicotine 7,4 mg; ENDDs containing nicotine 9 mg; ENDDs nicotine free; their usual cigarette. Additionally participants will be trained to use an electronic cigarette. The following tests will be completed at the each visits: Aldehydes; ROM/TOS; Total thiols; Nicotine; Hydroxypyrene; Cotinine; 1,3-butadiene; Acrylonitrile. After, they will be cannulated and serial venous blood samples for Aldehydes; ROM/TOS; Total thiols; Nicotine will be collected at 0.5, 2, 5, 15, 30 and 60 min after being instructed to take 10 puffs. Additionally, levels of carbon monoxide in exhaled breath (eCO) will be measured 0.5, 2, 5, 15, 30 and 60 min after being instructed to take 10 puffs. At 60 min, after being instructed to take 10 puffs, urine sample for Hydroxypyrene; Cotinine; 1,3-butadiene; Acrylonitrile will be collected. Participants then will leave the study centre with instructions to continue their usual daily activities and to use the study product regularly (for at least 10 hrs) and freely throughout the day. At bedtime and after the puffing chronic phase, when participants will use the study product regularly for at least 10 hrs, urine sample for Hydroxypyrene; Cotinine; 1,3-butadiene; Acrylonitrile will be collected. Participants will be allowed to smoke as they will wish once these measures will be collected and during the 3-day washout period between each study day.

Official Title
-----------------
Pharmacokinetic Profile of Toxic Substances and Nicotine in Electronic Cigarettes: a Randomised Cross-over Trial KINECIG

Conditions
-----------------
Tobacco Abuse Smoke

Intervention / Treatment
-----------------
* Other: Own Brand cigarette
* Other: one high 2,4% nicotine
* Other: original 7,4 mg nicotine
* Other: nicotine free
* Other: Ego 9mg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 20 regular smokers (smoking ≥ 15 factory-made cigarettes per day for at least the past 10 years and not currently attempting to quit smoking or wishing to do so in the next 30 days, CO > 10 parts per million ) will be recruited from the local Hospital staff in Catania, Italy. Exclusion Criteria: people who reported recent myocardial infarction, angina pectoris or other serious medical conditions (diabetes mellitus, severe allergies, poorly controlled asthma or other airways disease, poorly controlled psychiatric disorders or current chemical dependence other than nicotine) and pregnancy, breastfeeding, blood pressure > 180 mm Hg systolic and/or 100 mm Hg diastolic, weight < 45 or > 120 kg, or current use of any other smoking cessation medications

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Own Brand cigarette<br>Smoke Own Brand cigarette, 15 puff of cigarette. | Other: Own Brand cigarette<br>* Smoke, 15 puff of, Own Brand cigarettes;<br>Other: one high 2,4% nicotine<br>* Smoke, 25 puff, of electronic cigarette one high 2,4% nicotine<br>* Other names: Categoria electronic cigarette one high 2,4% nicotine;Other: original 7,4 mg nicotine<br>* Smoke, 15 puff, of Categoria electronic cigarette 7,4 mg nicotine<br>* Other names: Categoria electronic cigarette 7,4 mg nicotine;Other: nicotine free<br>* smoke, 15 puff, of electronic cigarette nicotine free<br>* Other names: categoria electronic cigarette nicotine free mint.;Other: Ego 9mg<br>* smoke, 15 puff, of electronic cigarette Ego 9 mg<br>* Other names: electronic cigarette Ego 9 mg nicotine;|
| Experimental: One High 2,4% nicotine<br>Smoke electronic cigarette One High 2,4% nicotine for a day, 15 puff of e-cigarette. | Other: Own Brand cigarette<br>* Smoke, 15 puff of, Own Brand cigarettes;<br>Other: one high 2,4% nicotine<br>* Smoke, 25 puff, of electronic cigarette one high 2,4% nicotine<br>* Other names: Categoria electronic cigarette one high 2,4% nicotine;Other: original 7,4 mg nicotine<br>* Smoke, 15 puff, of Categoria electronic cigarette 7,4 mg nicotine<br>* Other names: Categoria electronic cigarette 7,4 mg nicotine;Other: nicotine free<br>* smoke, 15 puff, of electronic cigarette nicotine free<br>* Other names: categoria electronic cigarette nicotine free mint.;Other: Ego 9mg<br>* smoke, 15 puff, of electronic cigarette Ego 9 mg<br>* Other names: electronic cigarette Ego 9 mg nicotine;|
| Experimental: Original 7,4 mg nicotine<br>Smoke electronic cigarette Original 7,4 mg nicotine for a day. 15 puff of e-cigarette. | Other: Own Brand cigarette<br>* Smoke, 15 puff of, Own Brand cigarettes;<br>Other: one high 2,4% nicotine<br>* Smoke, 25 puff, of electronic cigarette one high 2,4% nicotine<br>* Other names: Categoria electronic cigarette one high 2,4% nicotine;Other: original 7,4 mg nicotine<br>* Smoke, 15 puff, of Categoria electronic cigarette 7,4 mg nicotine<br>* Other names: Categoria electronic cigarette 7,4 mg nicotine;Other: nicotine free<br>* smoke, 15 puff, of electronic cigarette nicotine free<br>* Other names: categoria electronic cigarette nicotine free mint.;Other: Ego 9mg<br>* smoke, 15 puff, of electronic cigarette Ego 9 mg<br>* Other names: electronic cigarette Ego 9 mg nicotine;|
| Placebo Comparator: Nicotine Free<br>Smoke electronic cigarette nicotine free (15 puff) | Other: Own Brand cigarette<br>* Smoke, 15 puff of, Own Brand cigarettes;<br>Other: one high 2,4% nicotine<br>* Smoke, 25 puff, of electronic cigarette one high 2,4% nicotine<br>* Other names: Categoria electronic cigarette one high 2,4% nicotine;Other: original 7,4 mg nicotine<br>* Smoke, 15 puff, of Categoria electronic cigarette 7,4 mg nicotine<br>* Other names: Categoria electronic cigarette 7,4 mg nicotine;Other: nicotine free<br>* smoke, 15 puff, of electronic cigarette nicotine free<br>* Other names: categoria electronic cigarette nicotine free mint.;Other: Ego 9mg<br>* smoke, 15 puff, of electronic cigarette Ego 9 mg<br>* Other names: electronic cigarette Ego 9 mg nicotine;|
| Experimental: EGO 9mg<br>Smoke electronic cigarette EGO for a day (15 puff) | Other: Own Brand cigarette<br>* Smoke, 15 puff of, Own Brand cigarettes;<br>Other: one high 2,4% nicotine<br>* Smoke, 25 puff, of electronic cigarette one high 2,4% nicotine<br>* Other names: Categoria electronic cigarette one high 2,4% nicotine;Other: original 7,4 mg nicotine<br>* Smoke, 15 puff, of Categoria electronic cigarette 7,4 mg nicotine<br>* Other names: Categoria electronic cigarette 7,4 mg nicotine;Other: nicotine free<br>* smoke, 15 puff, of electronic cigarette nicotine free<br>* Other names: categoria electronic cigarette nicotine free mint.;Other: Ego 9mg<br>* smoke, 15 puff, of electronic cigarette Ego 9 mg<br>* Other names: electronic cigarette Ego 9 mg nicotine;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| nicotine pharmacokinetic | participants will be cannulated and serial venous blood samples for Nicotine will be collected at 0.5, 2, 5, 15, 30 and 60 min after being instructed to take 10 puffs of cigarette | 0 sec, 30 second, 2 minutes, 5 minutes, 15 minutes, 30 minutes, 60 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum levels of carcinogenic and toxic substances (Aldehydes; ROM/TOS; Total thiols) | Compare serum levels of carcinogenic and toxic substances of Categoria electronic cigarettes labelled Original 7,4 mg nicotine , Disposable Categoria electronic cigarettes labelled One 2,4% nicotine, Disposable Categoria electronic cigarettes labelled nicotine free, electronic cigarettes labelled Ego 9mg nicotine with usual cigarettes. | 0 sec, 30 second, 2 minutes, 5 minutes, 15 minutes, 30 minutes, 60 minutes |