Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized Controlled Trial of Varenicline for Adolescent Smoking Cessation
Brief Summary: This is a placebo-controlled smoking cessation treatment study for adolescents ages 14-21. After assessment and inclusion into the study, participants will be randomized to receive a 12-week double blind course of varenicline or placebo.


Options:
A: Inclusion Criteria:

* Healthy male and female adolescents (12 - 16 years inclusive) with a total body weight greater than 30 kg who currently smoke an average of at least 3 cigarettes per day.

Exclusion Criteria:

* Male and female subjects with a positive urine drug screen and female subjects with a positive pregnancy test.
B: Inclusion Criteria:

* daily tobacco smokers
* self-identify as Māori (indigenous New Zealander) or whānau (family) of Māori
* want to stop smoking in the next two weeks
* are at least 18 years of age
* are able to provide verbal consent
* reside in the Lakes District Health Board, Eastern Bay of Plenty or Tokoroa region at the time of enrolment
* have daily access to a mobile phone with text capability and/or email and access to the internet via computer or smartphone
* are eligible for subsidised varenicline under special authority conditions

Exclusion Criteria:

* are pregnant or breastfeeding
* are current users of other smoking cessation therapies (e.g. nicotine replacement therapy \[NRT\], buproprion \[Zyban\], clonidine, nortriptyline, e-cigarettes)
* are enrolled in another smoking cessation programme or another smoking cessation study
* have a contraindication for cytisine or varenicline
* have used varenicline or cytisine in the past 12 months
* have another person in their household involved in the trial
* have moderate or severe renal impairment,
* are being treated for active or latent TB
* have been treated for a heart attack, stroke, or severe angina within the last two weeks
* have uncontrolled high blood pressure (\> 150 mmHg systolic, \> 100 mmHg diastolic)
* have a history of seizures
C: Inclusion Criteria

1. 18 years of age or older who self-report smoking at least 5 cigarettes (menthol and non-menthol) per day, on average.
2. Diagnosed with HIV infection and exhibiting viral load of \< 1000 copies/mL and CD4+ counts of \> 200 cells/mm3 within 6 months prior to enrollment.
3. Able to use varenicline safely, based on a medical evaluation including medical history and physical examination, and psychiatric evaluation.
4. Residing in the geographic area for at least 7 months.
5. Women of childbearing potential (based on medical history and physical exam) must consent to use a medically accepted method of birth control (e.g., condoms and spermicide, oral contraceptive, Depo-Provera injection, contraceptive patch, tubal ligation) or abstain from sexual intercourse during the time they are taking study medication and for at least one month after the medication period ends.
6. If current or past diagnosis of bipolar disorder (I, II, or NOS), eligible if:

   1. No psychotic features
   2. MADRS: total score \< 8 (past 4 weeks), suicidal item score \< 1 (past 4 weeks)
   3. Y-MRS: total score \< 8 (past 4 weeks), irritability, speech content, disruptive, or aggressive behavior items score \< 3 (past 4 weeks)
   4. No psychiatric hospitalization or Emergency Room visits for psychiatric issues in the past 6 months
   5. No aggressive or violent acts or behavior in the past 6 months
7. Able to communicate fluently in English.
8. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the combined consent/HIPAA form.

Exclusion Criteria:

Smoking Behavior

1. Current enrollment or plans to enroll in another smoking cessation program in the next 7 months.
2. Regular (daily) use of chewing tobacco, snuff, snus, cigars, cigarillos, or pipes.
3. Current use or plans to use nicotine substitutes (gum, patch, lozenge, e-cigarette) or smoking cessation treatments in the next 7 months.

   1. Note: Once participants are found eligible for the study, they are told they should refrain from using any nicotine replacement therapy (NRT) for the duration of the study. If a subject reports an isolated (non-daily) instance of NRT use during the study, they may be permitted to continue.

Alcohol/Drug Exclusion Criteria

1. Current untreated and unstable diagnosis of substance abuse or dependence (eligible if past use and if receiving treatment and stable for \>30 days).
2. Positive urine drug screen (for cocaine and/or methamphetamines) at the Intake Session.
3. Breath Alcohol Concentration (BrAC) assessment greater than or equal to 0.01 at the Intake Session.

Medication Exclusion Criteria

Current use or recent discontinuation (within last 14 days) of the following medications:

1. Other smoking cessation medications (e.g. Zyban, Wellbutrin, Wellbutrin SR, Chantix)

   a. Note: Once participants are found eligible for the study, they are instructed to only use the smoking cessation medication provided to them by the study staff. If a subject reports an isolated (non-daily) instance of using a non-study smoking cessation medication, the study physician and PI will evaluate the situation and determine if it is safe for the subject to continue participation.
2. Anti-psychotic medications.

Medical Exclusion Criteria

1. Women who are pregnant, planning a pregnancy within the next 7 months, or lactating.
2. Current diagnosis of unstable and untreated major depression, as determined by self-report \& MINI (eligible if stable for \>30 days).
3. Current or past diagnosis of psychotic disorder, as determined by self-report or MINI.
4. Any suicide risk score on MINI, current suicidal ideation on Columbia scale, or self-reported lifetime suicide attempt.
5. History of heart disease, stroke or MI, unstable angina, or tachycardia (if stable, requires Study Physician approval).
6. Uncontrolled hypertension (SBP \>160 or DBP \>100).

   a. Note: If a participant presents with blood pressure greater than 160/100 at sessions occurring on Week 0 (Pre-Quit) or at any other point during the treatment period, they will not be provided with/able to continue on medication unless the study physician grants approval.
7. History of kidney or liver failure.
8. Abnormal ECG (unless approved by study physician).
9. Estimated creatinine clearance \<50 mL/min, within 6 months prior to enrollment.
10. AST and/or ALT results greater than 2 times the upper limit of normal, within 6 months prior to enrollment.
11. Any impairment (physical, neurological, visual) preventing cognitive task performance.
12. Previous allergic reaction to varenicline.

General Exclusion Criteria

1. Any medical condition or concomitant medication that could compromise subject safety or treatment, as determined by the Principal Investigator and/or Study Physician.
2. Inability to provide informed consent or complete any of the study tasks as determined by the Principal Investigator and/or Study Physician.
D: Inclusion Criteria:

* Age 14-21
* Daily smoker for ≥6 months
* Desire to quit smoking, with at least one prior failed quit attempt and willingness to participate in a treatment study
* If under age 18, parent(s) or guardian(s) able to participate in informed consent and initial assessment (unless the participant provides evidence of emancipated status)
* If female, agreement to use birth control (any form of hormonal contraception such as Depo-Provera, daily oral contraception, transdermal patch, or Nuva-ring; intrauterine device; sterilization; or double barrier contraception, which is a combination of any two of the following methods: condoms, spermicide, diaphragm) to avoid pregnancy

Exclusion Criteria:

* Lifetime history of any DSM-IV-TR mood or psychotic disorder (e.g., major depressive disorder, bipolar disorder, schizophrenia)
* Lifetime history of suicidality, homicidality, or clinically significant hostility/aggression
* Current substance dependence, other than nicotine
* Current unstable major medical disorder
* Current pregnancy or breastfeeding
* Current use of medications with smoking cessation efficacy
* Known hypersensitivity to varenicline

Answer: D