Please select the eligibility criteria that correspond to the clinical trial below.
Title: EVarQuit: Extended Pre-quit Varenicline to Assist in Quitting Smoking
Brief Summary: Varenicline is the most effective smoking cessation therapy available. Nevertheless, most smokers using varenicline relapse within the first few months after quitting. Varenicline is hypothesized to help smokers to quit in part by reducing the reinforcing effects of smoking during the standard 1-week pre-quitting treatment phase. Learning theory and previous human and animal research support the hypothesis that a longer period of varenicline treatment prior to the target quit date (TQD) will lead to greater reductions in smoking before quitting, and higher long-term cessation rates, compared to standard varenicline treatment. Building on promising preliminary clinical data, the study tests these hypotheses with a full-scale randomized clinical trial (RCT). 320 treatment-seeking smokers will be randomized to a standard run-in group (3 weeks of placebo, followed by the standard 1 week of pre-TQD varenicline) or an extended run-in group (4 weeks of pre-TQD varenicline). Both groups will receive brief individual cessation counseling and 11 weeks of post-TQD varenicline. The primary outcome measure will be bio-verified continuous abstinence at end-of-treatment (weeks 8-11 post-quit; cessation at 26-weeks post TQD will also be examined. Hypothesized mediating mechanisms (e.g., smoking reinforcement) will be evaluated by behavioral, physiological, and subjective measures assessed both in the lab and using real-world, real-time electronic momentary assessments (EMA). The investigators predict that long-term, bio-verified smoking cessation will be improved among the extended run-in group compared to the standard run-in group. The investigators further predict the improved clinical outcomes with extended run-in varenicline will be explained (or mediated) by greater pre-quit reductions in smoking reinforcement among the extended run-in group compared to the standard run-in group. The significance of this work is clear: The project aims to make best available treatment for smoking cessation even better, using a method that is ripe for dissemination and an approach that will elucidate critical mechanisms to target in the next generation of treatment enhancement.


Options:
A: Inclusion Criteria:

* Subjects will be eligible if they were randomized to study A3051123.

Exclusion Criteria:

* Participation in study A3051123 ceased (ie, withdrew consent, lost to follow-up, etc) prior to final visit of study A3051123.
B: Inclusion Criteria:

* Smoking at least 10 cigarettes per day (CPD) for the past 6 months and expired-air carbon monoxide (CO) \>7 at intake. NOTE: To reduce exclusion of Black participants, the CPD criterion was reduced to 5 and the carbon monoxide criterion was eliminated in November, 2019.
* At least moderately motivated to quit smoking and intention to make a quit attempt with varenicline 1 month after treatment begins.
* Planning to remain in western New York (NY) during the study period
* Willing to use varenicline and to refrain from other cessation treatments and tobacco products during the study period.
* English speaker
* To be intent-to-treat (ITT), the participant must complete Lab Visit 1 and meet minimal completion rate for real-world (EMA) assessments.

Exclusion Criteria:

* Use of other tobacco products, including e-cigarettes, in past 7 days
* Use of smoking cessation medication, including nicotine replacement therapy, in the past 14 days
* Prior allergy/hypersensitivity to varenicline
* Pregnant or breast-feeding
* Substance use:

  * Alcohol: AUDIT score \> 15 at intake, suggestive of alcohol dependence and warranting treatment; for those with scores between 8 and 15, the investigators will advise reducing drinking).
  * Medical treatment for substance use (SU) in past 3 months, including Suboxone (buprenorphine) and methadone (at phone screen)
  * Using a combination of the National Institute on Drug Abuse (NIDA) modified ASSIST (4-26 = moderate risk; 27+ = high risk) and urine toxicology screen (both at intake):

    * Cannabis: ASSIST=27+ (tox screen not used)
    * Cocaine: ASSIST=7+ OR positive tox screen
    * Methamphetamine: ASSIST=7+ OR positive tox screen
    * Inhalants, hallucinogens, sedatives, or sleeping pills: ASSIST score = 7+
    * Prescription stimulants: With prescription, ASSIST 27+; Without prescription, ASSIST 7+
    * Opioids: With prescription, ASSIST 27+ (note ineligible if prescription is for buprenorphine or methadone); Without prescription, ASSIST 7+ OR positive tox screen

(Note: ASSIST 4+ modified to 7+ in 2018 to avoid excluding people with past SU problems. clinicaltrials.gov edited 12/18/18)

* Psychiatric:

  * Antipsychotic medications
  * Lifetime history of schizophrenia or bipolar disorder
  * Evidence of current major depression (per Patient Health Questionnaire (PHQ-9) at intake
  * Past 10 years suicidal ideation (SI) / behavior. At intake, all of the following are exclusionary on the baseline Columbia-Suicide Severity Rating Scale (Posner et al., 2008): SI without intent (C-SSRS #1, #2, or #3), if any intensity rating (Frequency, Duration, Controllability, Deterrents, or Reasons for Ideation) is \> 2; SI with intent (C-SSRS #4, or #5), regardless of intensity ratings; Suicidal Behavior (any suicide attempt, interrupted attempt, aborted attempt, or suicide preparatory acts or behavior on the C-SSRS).
* Any medical condition, illness, disorder or concomitant medication that compromises participant safety or treatment, as determined by the Principal Investigator and/or Study Physician.
* Inability to provide informed consent or complete any of the study tasks as determined by the Principal Investigator and/or Study Physician.
C: Inclusion Criteria:

* Age 18 years or older
* English speaking
* Smoked at least 100 cigarettes/lifetime
* Smoke 5 or more cigarettes per day
* Interested in quitting smoking (preparation or contemplation stage of change)
* Enrolled in Einstein/Montefiore methadone program for 12 weeks or more
* Receiving methadone in clinic three, four, five or six times per week
* No more than 2 methadone clinic misses in prior 14 days
* Agree to use contraception for the duration of the trial (among women with reproductive potential)
* Willing to participate in all study components
* Able to provide informed consent

Exclusion Criteria:

* Serious or unstable HIV/AIDS, liver, cardiovascular, or pulmonary disease
* Psychiatric instability
* Women who are pregnant, breastfeeding, or contemplating pregnancy
* Creatinine clearance \<30 mL/min
D: Inclusion Criteria:

* Male or female cigarette smokers, 18- 75 years, motivated to stop smoking and considered suitable for a smoking cessation attempt.
* Smoked an average of at least 10 cigarettes per day during past year and during the month prior to the screening visit, and exhaled carbon monoxide (CO) \>10 ppm at screening.
* For Neuropsychiatric cohort- subjects must have proper diagnosis as outlined in protocol.

Exclusion Criteria:

* Subjects with a past or current diagnosis of one of the following disorders:

  a. Psychotic Disorders:
* Schizophreniform
* Delusional Disorder
* Psychotic Disorder NOS b. All Delirium, Dementia, and Amnestic and Other Cognitive Disorders c. All Substance Induced Disorders (Other than nicotine)

Answer: B