Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomised Controlled Trial Investigating the Efficacy and Safety of an Electronic Nicotine Delivery Device (E-Cigarette) in Smokers
Brief Summary: The study's major aim is to investigate the ability of a commercial Electronic Nicotine Delivery Device (E-Cigarette) to induce long-term smoking reduction/abstinence in smokers unwilling to quit. Secondary aims are to investigate changes in withdrawal symptoms and cravings and to examine whether concomitant use of the E-Cigarette and smoking is safe.

The study will monitor smoking reduction/abstinence effects, changes in withdrawal symptoms, and adverse events of a currently marketed device in Italy ("Categoria" electronic cigarette - "ORIGINAL" 7.2 mg nicotine cartridges).

The primary hypothesis is that the E-Cigarette is a safe device that allows smoking reduction or abstinence in smokers possibly by suppressing withdrawal symptoms and cravings.


Options:
A: Inclusion Criteria: healthy smokers unwilling to quit, between 18 and 60 years of age. They should report a cigarette intake of ≥ 15 cig/day for at least 5 years. At screening they must provide a CO level of ≥ 15 ppm and an FTND ≥ 5.

Exclusion Criteria: alcohol and illicit drug use, breastfeeding, or pregnancy. Individuals who report current attempts to quit smoking and previous experience with electronic cigarettes will be also excluded.
B: Inclusion Criteria:

* Age 18+
* Smoke an average of at least five cigarettes per day for at least 1 year
* Breath CO levels \> 8 ppm (if ≤ 8 ppm, then NicAlert Strip \> 2)

Exclusion Criteria:

* Intention to quit smoking in the next 30 days
* Currently seeking treatment for smoking cessation
* Currently using nicotine replacement therapies or other pharmacotherapies as cessation aid (intermittent use acceptable)
* A quit attempt in the past 30 days resulting in greater than 3 days of abstinence
* Using other tobacco products more than 9 days in the past 30 days
* Significant unstable medical conditions (Any significant change in a serious medical condition occurring during the past 3 months including, cardiovascular disease, COPD, and cancer, as determined by the licensed medical professional at each site)
* Significant unstable psychiatric conditions (Any significant change in psychiatric symptoms during the past 3 months as determined by the licensed medical professional at each site)
* Schizophrenia and schizoaffective disorder
* Psychiatric medication changes in the past 3 months
* Positive toxicology screen for any of the following drugs: cocaine, opiates, methadone, benzodiazepines, barbiturates, amphetamines, methamphetamines, and PCP

  1. Marijuana will be tested for but will not be an exclusionary criterion.
  2. Participants with valid prescriptions for opiates, benzodiazepines, barbiturates, amphetamines or methadone will not be excluded.
  3. Participants failing the toxicology screen will be allowed to re-screen once.
* Blood alcohol level \> 0.01

  a. Participants failing the blood alcohol screen will be allowed to re-screen once.
* Binge drinking alcohol (more than 9 days in the past 30 days, 4/5 in a 2 hour period(female/male))
* Pregnant or breastfeeding
* Smoking 'roll your own cigarettes' exclusively
* Currently taking anticonvulsant medication
* CO reading \>80 ppm
* Systolic BP greater than or equal to 160

  a. Participants failing for blood pressure will be allowed to re-screen once.
* Diastolic BP greater than or equal to 100

  a. Participants failing for blood pressure will be allowed to re-screen once.
* Systolic BP below 90

  a. Participants failing for blood pressure will be allowed to re-screen once.
* Diastolic BP below 50

  a. Participants failing for blood pressure will be allowed to re-screen once.
* Heart rate greater than or equal to 115bpm

  a. Participants failing for heart rate will be allowed to re-screen once.
* Heart rate lower than 45bpm

  a. Participants failing for heart rate will be allowed to re-screen once.
* Indicating any suicidal ideation in the past month or suicide attempts in the past 10 years
* Inability to independently read and comprehend the consent form and other written study materials and measures
* Having participated in a research study during the past three months in which the participant:

  1. Smoked a cigarette that was not his/her usual brand cigarette for more than one day
  2. Used any tobacco products beyond normal use for more than one day
  3. Used any nicotine replacement products or smoking cessation medications for more than one day
C: Inclusion Criteria:

1. Smokers smoking at least 10 cigarettes/day (factory made or roll-your-own) in the past year
2. Aged 18 to 70 years
3. Motivated to quit defined as a score \> 5 on a visual rating scale ranging from 0 (not motivated at all) to 10 (extremely motivated)
4. Signed written informed consent
5. Understanding and speaking French
6. Women of childbearing age can be included if they use an effective contraceptive method: either hormonal contraception or an intrauterine device started at least one month before the first research visit
7. Individual affiliated to a health insurance system as defined by the sponsor (except Aide Médicale d'État =AME)
8. Previous failure of nicotine replacement therapy for smoking cessation

Exclusion Criteria:

1. any unstable disease condition within the last 3 months defined by the investigator as major change in symptoms or treatments such as 1.1.recent myocardial infarction, 1.2.unstable or worsening angina 1.3.severe cardiac arrhythmia 1.4.unstable or uncontrolled arterial hypertension 1.5.recent stroke 1.6.cerebrovascular disease 1.7.obliterative peripheral arterial disease 1.8.cardiac insufficiency 1.9.diabetes 1.10.hyperthyroidism 1.11.pheochromocytoma 1.12.severe hepatic insufficiency 1.13.history of seizures 1.14.severe depression 1.15.chronic obstructive pulmonary disease (COPD)
2. any life threatening condition with life-expectancy of less than 3 months
3. alcohol use disorder defined as a score ≥ 10 on the AUDIT-C questionnaire
4. abuse of or dependence on illegal drugs in the last 6 months revealed by the medical history
5. regular use of tobacco products other than cigarettes
6. current or previous (last 6 months) use of electronic cigarette
7. pregnant women
8. breastfeeding women
9. protected adults
10. current or past 3 months participation in another interventional research
11. current or past (last 3 months) use of smoking cessation medication such as varenicline, bupropion, nicotine replacement therapies
12. known lactose intolerance (placebo tablets contain lactose)
13. hypersensitivity to the active substance or to any of the excipients
14. known severe renal failure
D: Inclusion Criteria:

* Healthy on the basis of medical history
* Current moderate-to-heavy smoker as determined by:

  * Has smoked \>=10 cigarettes per day regularly for the past year (by history) and (\>=5 cigarettes per day Study 2 ONLY)
  * Has an expired carbon monoxide (CO) at screening visit of 8 parts per million (ppm) or more (6 ppm or more Study 2 ONLY)
* Nicotine dependence assessed as \> 4 with the Fagerstrom Test for Nicotine Dependence
* Willingness to abstain from smoking for 8 hours (overnight abstinence) prior to study visits
* Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

* Unstable medical conditions (such as unstable heart disease, uncontrolled hypertension, thyroid disease, diabetes, renal or liver impairment, glaucoma, or prostatic hypertrophy) or psychiatric condition (such as current major depression, history of schizophrenia or bipolar disorder, or current regular use of psychiatric medications such as major tranquilizers and antidepressants
* Pregnancy or lactation (by history) or positive pregnancy test at screening visit
* Positive urine drug test at screening visit
* History of serious side effects from nicotine or from any nicotine replacement therapies
* Alcohol or illicit drug dependence within the past 12 months (by history and urine tests)
* Concurrent participation in another clinical trial
* Unable to communicate in English
* Unwilling or unable to follow protocol requirements
* Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study intervention

Answer: A