Efficacy and Safety of High Dose Baclofen for Alcohol Dependence
Condition: Alcoholism
MeSH terms: Alcoholism
Intervention: Baclofen; Placebo
Intervention description: Baclofen is a GABA-B agonist; Pill containing no pharmacologically active substance.
Intervention MeSH terms: Baclofen
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 120.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Baclofen; Alcohol Dependence

Summary:

      The proposed study will carefully test the hypothesis that a robust dose of baclofen (90
      mg/day) has efficacy and is safe in individuals with alcohol dependence. Furthermore, the
      proposal will test whether an indicator of physical dependence, i.e. drinks/drinking day,
      predicts response to baclofen. Additionally, the proposal will examine the anti-anxiety
      effects of baclofen within an alcohol dependent population and ascertain whether baseline
      levels of anxiety predict response to baclofen.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Men and women between the ages of 18 and 65 meeting Diagnostic and Statistical Manual
             (DSM)-IV criteria for current alcohol dependence.

          2. More than 14 drinks (women) or 21 drinks (men) per week including at least 2 heavy
             drinking days (men > 5 drinks/day; women > 4 drinks/day) per week in the 30-day period
             prior to screening. In addition we will recruit 50% of individuals who have a mean of
             ≥14 drinks/drinking day (men) or ≥10 drinks/drinking day (women) in the 30 days prior
             to screening.

          3. Ability to understand and sign written informed consent.

          4. Must have a 0.0 gms/dL breathalyzer reading on the day of screening and 0.0 gms/dL on
             the day of randomization.

          5. Express a desire to achieve abstinence or to greatly reduce alcohol consumption

          6. Must have a stable residence and be able to identify an individual who could contact
             participant if needed.

        Exclusion Criteria:

          1. Clinically significant medical disease that might interfere with the evaluation of the
             study medication or present a safety concern (e.g., renal insufficiency, cirrhosis,
             unstable hypertension, diabetes mellitus, seizure disorder). Clinically significant
             psychiatric illness including any psychotic disorder, bipolar disorder, severe
             depression, or suicidal ideation.

          2. Other substance abuse or dependence disorder other than nicotine or alcohol or
             cannabis abuse.

             Occasional use of cocaine is acceptable.

          3. Concurrent use of any psychotropic medication including antidepressants, mood
             stabilizers, antipsychotics, anxiolytics, stimulants, or hypnotics with the exception
             of stable doses of antidepressants for one month. Concurrent use of anticonvulsants,
             insulin, or oral hypoglycemics.

          4. Prior history of adverse reaction to baclofen.

          5. Creatinine level > Upper Limit of Normal (ULN) or Estimated Glomerular Filtration Rate
             < age norm.

          6. aspartate aminotransferase (AST), or alanine transaminase (ALT) > 5 times ULN or
             bilirubin > 1.5 X ULN.

          7. Positive urine toxicology screen with the exception of cannabis. Individuals with
             positive cannabis screens will be excluded only if they have a history of cannabis
             dependence.

          8. Pregnant women and women of childbearing potential who do not practice a medically
             acceptable form of birth control (oral or depot contraceptive, or barrier methods such
             as diaphragm or condom with spermicidal).

          9. Women who are breastfeeding.

         10. Individuals requiring inpatient treatment or more intense outpatient treatment for
             their alcohol dependence.

         11. Participation in any clinical trial within the past 60 days.

         12. Court-mandated participation in alcohol treatment or pending incarceration.