Prometa Protocol for Alcohol Dependence
Condition: Alcohol Dependence
MeSH terms: Alcoholism
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      This is a placebo controlled trial (some people receive active and some people receive
      inactive medication) to evaluate the effectiveness of a new protocol to treat alcohol
      dependence. Two main medications (plus ancillary non-placebo controlled medications) and
      their placebos (inactive drugs) will be utilized to treat both alcohol withdrawal, promote
      abstinence, and reduce drinking over approximately a six-week treatment period. All
      participants will meet criteria for Alcohol Dependence and be drinking heavily up until 72
      hours prior to receiving the first study drug. They will be injected one drug (flumazenil or
      placebo) over a two day period and receive the second one (gabapentin or placebo) by mouth
      for 39 days. The main hypothesis is that this protocol will reduce early alcohol withdrawal
      symptoms and will reduce relapse to drinking and promote abstinence compared to the placebo
      (inactive) drug group. Secondary outcomes that will be evaluated include reduction in
      craving, improvement in sleep, brain activity and mood.
    

Detailed description: 
      Approximately 60 alcohol dependent individuals who are drinking heavily up until 72 hours, or
      less, prior to study participation will be randomized to receive either flumazenil
      (intravenously)on two successive days and gabapentin (orally)for 39 days or their matching
      placebos. They also will receive hydroxyzine and vitamins. Individuals will be evaluated for
      alcohol withdrawal, their response to acoustic startle, cognitive ability, craving, mood,
      sleep and drinking during the first week. They will then be seen weekly for about 6 weeks
      during which they take gabapentin or placebo and are provided with Combined Behavioral
      Intervention Therapy (counseling) once a week, or more, as required. Over this period they
      will be evaluated weekly for alcohol consumption, craving, sleep, mood, and biological
      markers of alcohol consumption ( percent carbohydrate deficient transferrin and
      gamma-glutamyl transferase). Blood will be obtained on week 3 and 6 for general health
      (liver, blood count etc.) screening. After the end of treatment, subjects will be followed-up
      at 4 weeks and again at 8 weeks after treatment to evaluate alcohol consumption, craving,
      sleep, mood.

      Subjects will undergo a functional magnetic resonance imaging (MRI) procedure sometime during
      the second or third week of study medication to assess cue induced regional brain activation
      to investigate the effect of medication on brain response to alcohol visual cues.
    

Intervention name(s): Flumazenil and Gabapentin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 2 mg flumazenil for infusion given slowly over 20 minutes given day 1 and day 2 gabapentin 300 mg increasing to 1200 mg over 4 days and continuing to day 30. Gabapentin 900 mg Day 31 to Day 33 gabapentin 600 mg Day 34 to 36 and gabapentin 300 mg Day 37 to 39.; 20 mg Saline infused slowly over 20 minutes. Placebo 1 capsule Day 1, 2 capsules Day 2, 3 capsules Day 3, 4 capsules days 4 to 30; 3 capsules Day 31 to 33; 2 capsules day 34 to 36 and 1 capsule 37 to 39.
Intervention MeSH terms: Gabapentin; Flumazenil
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Alcoholism; Alcohol Dependence; Alcohol Withdrawal; Treatment; Pharmacotherapy