EVarQuit: Extended Pre-quit Varenicline to Assist in Quitting Smoking
Condition: Tobacco Smoking
Intervention: Varenicline; Brief smoking cessation counseling
Intervention description: oral varenicline tablets; ~10-minute individual counseling at each of 6 clinic visits
Intervention MeSH terms: Varenicline
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 320.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: Accepts Healthy Volunteers

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.
    

Eligibility criteria:

        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.