Efficacy and Safety of High Dose Baclofen for Alcohol Dependence
Condition: Alcoholism
MeSH terms: Alcoholism
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      Alcohol dependence (AD) is a common problem with significant health consequences. Treatment
      of AD is evolving to include both counseling methods and medications. Several medications
      have been discovered, that show efficacy in AD, e.g. naltrexone, acamprosate. However, the
      overall effect of existing medications is modest leaving a clear need for the development of
      new pharmacotherapies. The gamma-aminobutyric acid (GABA)-B receptor agonist baclofen has
      attracted attention as a potential new medication for AD based on preclinical data and early
      clinical trials. Baclofen is an FDA approved medication with an excellent safety profile even
      for patients with liver cirrhosis-a not uncommon consequence of AD. Questions have arisen
      with regards to the efficacy of baclofen and whether higher doses of baclofen are safe and
      more effective than the prior tested dose of 30 mg/ day. There is emerging evidence that
      severity of dependence is positively associated with baclofen response. The main goal of the
      present proposal is to test the efficacy and safety of 30 mg/d and 90 mg/d of baclofen
      compared to placebo controlling for severity of dependence as assessed by drinks/drinking
      day. A primary secondary goal will examine for an anxiolytic effect of baclofen. The study
      proposes to enroll 120 men and women with AD in a randomized, placebo-controlled trial to
      include at least 60 individuals with more severe AD (≥14 drinks/drinking day for men; ≥10
      drinks/drinking day for women) with randomization to baclofen or placebo balanced for this
      variable. Baclofen will be titrated to 10 mg t.i.d over 3 days and to 30 mg t.i.d over 12
      days and maintained at that level for 12 weeks and then downtitrated for a total study time
      of 16 weeks. Medical Management will be provided to encourage progress towards drinking goals
      and to enhance retention and compliance. Drinking patterns, anxiety levels, sleep patterns,
      craving for alcohol, gamma-glutamyl transferase (GGT) and carbohydrate deficient transferring
      (CDT) will be assessed. Trough blood levels of R & S-baclofen will be assessed in all
      individuals at week 4.

      In summary, the present proposal is innovative and of clinical significance as it will test
      and compare standard and high-dose baclofen for efficacy and safety in individuals with AD.
      The proposal is adequately powered to test the primary hypothesis and provides good power to
      assess whether drinks/drinking day is predictive of baclofen response. Adequate power is also
      present to examine the anxiolytic effect of baclofen. Ascertaining the effects of standard
      and high-dose baclofen, the predictive value of heavy drinking on baclofen response and the
      anxiolytic effect of baclofen are important goals towards determining whether baclofen has
      true value for the clinical management of the patient with alcohol dependence.
    

Intervention name(s): Baclofen; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Baclofen is a GABA-B agonist; Pill containing no pharmacologically active substance.
Other intervention name(s): Lioresal; Sugar pill
Intervention MeSH terms: Baclofen
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Baclofen; Alcohol Dependence