Please select the eligibility criteria that correspond to the clinical trial below.
Title: Varenicline Treatment for Active Alcoholic Smokers
Brief Summary: Alcohol dependence is a significant and prevalent public health problem affecting approximately 4% of the U.S. adult population. Individuals with alcohol dependence actively seek treatment annually, and long-term alcohol abstinence varies from 40-60%. Because of the high smoking prevalence and trends toward heavier smoking, alcoholic smokers are at high risk for both morbidity and mortality related to alcohol consumption and tobacco dependence. Although several studies have evaluated pharmacotherapy for tobacco dependence in recovering alcoholic smokers, few have evaluated pharmacotherapy for tobacco dependence among currently drinking alcoholic smokers.

Varenicline is the most effective medication currently available for treating tobacco dependence. While some randomized trials have included recovering alcoholics, active alcoholism has been an exclusion criteria for these trials. Thus, this proposal would be the first such clinical trial in currently drinking alcoholic smokers. In addition to helping smokers to stop smoking, varenicline has also been shown to reduce alcohol consumption in rats. The goal of this proposal is to explore the potential efficacy of varenicline for treating tobacco dependence and reducing drinking among alcohol dependent smokers.

The investigators hypothesize that 12 weeks of treatment with varenicline, a partial nicotinic acetylcholine receptor agonist will be more effective than placebo in treating tobacco dependence and reducing nicotine withdrawal symptoms in currently drinking alcoholic smokers. The investigators will also explore whether varenicline has an effect on drinking behavior among currently drinking alcoholics. The investigators propose the following specific aims to test these hypotheses in 70 currently drinking alcoholic smokers recruited at the Mayo Clinic in Rochester, Minnesota.


Options:
A: Inclusion Criteria:

* Meet DSM-IV criteria for nicotine dependence with FTND score \> 5.
* Smoke at least 15 cigarettes (3/4 pack) daily (averaged over 1 week, in the past 1 month).
* At the time of initial evaluation, are motivated to quit smoking in the next 30 days.
* Have made at least one unsuccessful attempt to quit smoking in the past year.
* At baseline, have expired breath CO level \> 10.
* Are between ages 18-70 years old.
* Weigh at least 100 lbs (45.5 kg, selegiline dose \< 0.22 mg/kg).
* No previous use of nicotine replacement products in the one month prior to randomization.
* Have the capacity to give informed consent, and are English-speaking.

Exclusion Criteria:

* Have present or past diagnoses of schizophrenia, bipolar disorder, PTSD, BPD or major depressive illness.
* Have abused alcohol or other drugs of abuse (cocaine, opiates, benzodiazepines, etc) in 6 months prior to randomization into the trial (based on clinical evaluation including self-report, and confirmed by positive urine).
* Demonstrate serious medical conditions (i.e. abnormal liver function \[as evidenced by AST, ALT or bilirubin values 2x ULN\], unstable cardiovascular disease, significant blood abnormalities).
* Exhibit or have history of clinical hypertension.
* Exhibit active peptic ulcer disease.
* Are pregnant, are trying to become pregnant, or are currently breastfeeding.
* Are on current medication regimes that include antidepressants, or sympathomimetic agents, or meperidine and other meperidine-opioids which may have interactions with selegiline.
* Known hypersensitivity to selegiline or NRT.
* Are from the same household as another study participant.
B: Inclusion Criteria:

1. Male or non-pregnant female cigarette smokers 18-years-of-age or older and reporting smoking at least an average of 10 cigarettes per day for the past year;
2. Subject is alcohol dependence based on DSM IV criteria as assessed by the Mini-International Neuropsychiatric Interview (MINI) and the physician investigator;3
3. Subject is currently drinking alcoholic beverages as assessed by the physician investigator;
4. Subject is a female subject of non-childbearing potential or a female subject of childbearing potential - who is using contraceptives and has a negative pregnancy test result;
5. Subject must be able to complete all the study visits;
6. Subject has the ability to participate fully in all aspects of the study and keep scheduled appointments;
7. Subject must be in good general health as determined by medical history, physical exam and physician investigator;
8. Subject must provide written informed consent to participate in the study;

Exclusion Criteria:

1. Subject is a female who is pregnant, lactating or likely to become pregnant during the trial and not willing to use an acceptable form of contraception during the medication phase, (for women of child-bearing potential, a pregnancy test will be performed prior to entry into the study and at the end of the medication phase);
2. Subject has another household member in study;
3. Known allergy to varenicline;
4. Subject is currently (in previous 30 days) using other behavioral or pharmacologic tobacco cessation program (i.e., behavioral therapy, nicotine replacement therapy, clonidine, varenicline, bupropion SR, nortriptyline or doxepin) and unwilling or unable to discontinue use;
5. Subject has an unstable medical condition as determined by the physician investigator;
6. Subject describes having a medical history of: a) unstable angina; b) myocardial infarction within the past 3 months; c) coronary angioplasty or d) an untreated cardiac dysrhythmia;
7. Subject has a personal history of renal failure or is on renal dialysis;
8. Subject has a current moderate or severe depression as assessed by the Center for Epidemiologic Studies-Depression survey (CES-D) and physician investigator;
9. Subject has, as defined by the Columbia Suicide Severity Rating Scale (C-SSRS) current non-specific suicidal thoughts, or have a lifetime history of a suicidal attempt (defined as "potentially self-injurious act committed with at least some wish to die, as a result of act");
10. Subject has current (past 30 days) major depressive disorder or has a history of another psychiatric disorder such as psychosis or bipolar disorder;
11. Subject currently uses of other tobacco products (i.e. pipe, cigar, smokeless tobacco) within the past 30 days;
12. Subject currently has cancer \[excluding non melanoma skin cancer\] not in remission (cancer free for 5 years or more);
13. Subject currently has Type 1 diabetes;
14. Subject has untreated hypertension or baseline systolic blood pressure \> 180 or diastolic \> 100;
15. Subject is currently on treatment with another investigational drug (within 30 days of study entry);
C: Inclusion Criteria:

* \>18 years old,
* had smoked \>1 cigarette in the past month,
* were admitted to the hospital with a diagnosis of acute cardiovascular disease (see below)
* had an expected hospital stay of \>24 hours.

Eligible admission diagnoses included (1) acute ischemic coronary heart disease (MI or unstable angina), (2) coronary artery bypass graft surgery, or (3) other cardiovascular conditions (congestive heart failure, cardiac arrhythmia, valvular heart disease, or atherosclerotic disease of the aorta, carotid, renal or peripheral arteries) in subjects with documented coronary artery disease.

Exclusion Criteria:

* not willing to consider smoking cessation after discharge,
* a contraindication to bupropion (seizure disorder, monoamine oxidase inhibitor use, history of anorexia nervosa or bulimia, bupropion allergy)
* a condition that increased the risk of seizure (e.g., serious head trauma with loss of consciousness
* uncontrolled hypertension (BP \>160/100) in hospital
* heavy alcohol use (\>3 drinks/day) or binge drinking (\>6 drinks for males or \>5 drinks for females) at least monthly
* renal insufficiency (serum creatinine \>2.0 mg/dl),
* severe hepatic disease
* severe depression or severe cognitive impairment or psychosis
* life expectancy of \<12 months,
* illegal drug use in the past 6 months
* bupropion use in the past month
* non-English speaking
* no telephone
* residence outside a defined geographic area.
D: Inclusion Criteria:

* age \>=18 years; smoking \>4 cigarettes/day for the previous 6 months; able to read, write, and speak English; have reliable phone access and agree to respond to Interactive Voice Response (IVR) phone prompts; and if currently using NRT, agreeing to use only study medication for the duration of the study. We will not exclude participants based on their prior use of cessation medication or if they use multiple tobacco products in order to enhance real-world generalization (these will be statistically controlled in analyses); not currently attempting to quit smoking; not intending to quit smoking (defined as no plans to quit in the next month); and planning to remain in the intervention catchment area for at least 12 months.

Exclusion Criteria:

* currently taking bupropion or varenicline; medical contraindications to using NRT including hospitalized (for at least one night) for a stroke, heart attack, congestive heart failure or diabetes in the last 30 days; diagnosis of or treatment for schizophrenia, a psychotic disorder or bipolar disorder in the last 10 years; and, if the participant is a woman of childbearing potential, being pregnant or intending to becoming pregnant or unwillingness to use an approved method of birth control during treatment.

Answer: B