Buproprion for Binge Drinking
Condition: Alcohol Abuse
MeSH terms: Alcoholism; Binge Drinking
Study type: Interventional
Phase: Phase 2

Summary: 
      The present proposal is an innovative and translational clinical trial derived from exciting
      preclinical findings to test the hypothesis that treatment with the melanocortin activator
      bupropion can reduce binge drinking in humans. Furthermore, pilot data on moderating effects
      of coexisting nicotine use on the efficacy of bupropion for binge drinking population will be
      obtained. Evidence for an efficacy signal with good tolerability with this FDA approved
      medication would form the foundation to conduct a well-powered Phase II b trial. The
      development of an effective pharmacotherapy for binge drinking would be a significant
      clinical advance.

      .
    

Detailed description: 
      The design is a 1:1 random assignment to placebo or bupropion XL (extended release)
      (300mg/d). The study biostatistician, will prepare the randomization schedule and include
      blocking by gender and nicotine dependence. Randomization will be based on a stratified block
      design, with gender and nicotine dependence as the stratification variables with
      medication/placebo randomly assigned in blocks of four.

      Bupropion XL will be initiated at 150 mg/d on Days 1-4 and increased to 300 mg/d for Days
      5-84. The University of North Carolina (UNC) Hospital's Investigational Drug Services (IDS)
      will prepare opaque capsules containing bupropion XL 150/300 mg and matching placebo.
      Capsules will be inserted into blister packs with each pack containing 1 week of medication.
      The IDS will receive the randomization schedule from our statistician and prepare the blister
      packs according to the blocked schedule with blocking for gender/nicotine dependence.

      Recruitment, Telephone Screen, and Full Eligibility Screening: Subjects will initially be
      prescreened by phone and then at full screening read and sign the informed consent. A
      breathalyzer test will be administered (must be 0.00 gms/dl to give informed consent),
      height, weight and BMI recorded and a medical history and examination completed.
      Over-the-counter and prescription medication use will be recorded and nicotine use
      documented. Complete Blood Count (CBC) with differential; serum bilirubin, Aspartate
      Aminotransferase (AST), Alanine Aminotransferase (ALT), Gamma-Glutamyl Transferase (GGT,)
      sodium, potassium, chloride, blood urea nitrogen, creatinine, glucose; and urinalysis and
      urine toxicology completed. Women will be given a urine pregnancy test (Ub-HCG) at screening
      and at weeks 4, 8, and 12. Trained interviewers will conduct the psychiatric screening
      interview using the M.I.N.I. . The Structured Clinical Interview (SCID) Substance Use
      Disorders Module to establish Diagnostic and Statistical Manual (DSM-V) criteria for alcohol
      use disorders will be administered by one of the study doctors. The study coordinator will
      conduct the pretreatment 90-day Timeline Followback (TLFB) interview to identify amount of
      alcohol consumed and timeframe of consumption. A binge drinking episode requires a minimum of
      5/4 (men/women) standard drinks consumed over about a two hour period, i.e. consuming a
      bottle of wine over five hours would not be coded as a binge drinking day. The Penn Alcohol
      Craving Scale (PACS) and the University of Rhode Island Change Assessment (URICA) will be
      completed and treatment goal-abstinence vs. reduction- recorded.

      Initial Treatment Visit (within 21 days screening): Eligible individuals will not be required
      to abstain from drinking alcohol prior to randomization. The study coordinator will
      administer a breathalyzer test (BAC must be ≤0.04 gms/d) and complete assessments as outlined
      in Table 1, Protection of Human Subjects. A salivary cotinine sample will be taken A 1-week
      blister pack of bupropion-XL or placebo with written instructions will be dispensed from the
      Investigational Drug Services according to the randomization block along with a 1-week
      back-up blister pack in case of delayed appointments or lost doses. Bupropion-XL will be
      titrated with 150 mg given daily for 4 days followed by 300 mg/d. Participants will be given
      a calendar style diary to track pill taking, drinking quantity/timing, intoxication and any
      side effects. Finally, participants will receive Medical Management from a trained clinician.

      Subsequent Treatment Visits: TLFB and PACS are gathered each visit, cotinine samples at weeks
      4, 8 and 12 and URICA at week 8. Medical monitoring will be conducted by study physicians and
      will consist of review of vital signs, concomitant medication use, and general inquiries into
      side effects. The physician may recommend that medication be held for a period of time to
      deal with an adverse event, e.g. nausea. One month and three months following the last visit
      subjects will be contacted by phone to update drinking (TLFB), adverse effects and
      medications.

      Medical Management Intervention: The psychosocial support for the study will be Medical
      Management (MM). MM sessions average 10-15 minutes and focus on three main areas: (1)
      feedback on consequences of drinking; (2) encouraging compliance with medication/addressing
      compliance problems and (3) encouraging progress towards drinking goal- reduction or
      abstinence are acceptable. 10% of sessions will be audiotaped and reviewed to enhance
      fidelity.

      Medication Compliance Monitoring: Participants will record their pill taking in
      calendar-style diaries that will be provided and collected at each visit. Pills will be
      distributed in blister packs that will be returned to the study coordinator to reconcile any
      unused medication from the returned blister packs with participants' diary records.
    

Intervention name(s): Bupropion; Placebo Oral Tablet
Intervention type(s): Drug; Drug
Intervention description(s): Bupropion XL will be initiated at 150 mg/d on Days 1-4 and increased to 300 mg/d for Days 5-84.; Placebo will be initiated on Day 1 and continue throughout the course of the study.
Other intervention name(s): Wellbutrin Extended Release; Sugar pill
Intervention MeSH terms: Bupropion
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment