Baclofen for Treating Anxiety and Alcoholism
Condition: Alcoholism; Alcohol Dependence; Alcohol Drinking Related Problems; Alcohol Drinking; Anxiety Disorder
MeSH terms: Alcoholism; Anxiety Disorders; Alcohol Drinking
Study type: Interventional
Phase: Phase 2

Summary: 
      Background:

      - Baclofen is a drug used to control muscle stiffness in people with neurological diseases.
      Some studies suggest that baclofen may reduce alcohol craving and use. It helps to reduce
      anxiety in alcoholics, which in turn can help to reduce cravings. Researchers want to see if
      baclofen can be a safe and effective treatment for alcoholics who have high anxiety levels.

      Objectives:

      - To see if baclofen is safe and helpful for people who have alcoholism and high anxiety
      levels.

      Eligibility:

        -  Individuals between 21 and 65 years of age who have been diagnosed with alcoholism and
           anxiety issues.

        -  Participants must not be taking anti-anxiety medication.

      Design:

        -  Participants will be screened with a physical exam and medical history. Blood and urine
           samples will be collected. Tests of alcohol dependency and anxiety levels will also be
           given.

        -  Participants will be divided into two groups. One group will take baclofen. The other
           group will have a placebo.

        -  About 1 week after the screening visit, participants will have a study visit. They will
           answer questions about their behavior and mood. They will then start to take either
           baclofen or a placebo. Participants will take the study drug three times a day, every
           day.

        -  After 1 week on the study drug, participants will have an overnight stay at the National
           Institutes of Health. They will have blood tests and answer questions about mood and
           behavior. They will also have tests that involve choosing to drink alcohol and answering
           more questions about cravings.

        -  Participants will stop taking their study drug over a 3-day period.

        -  A final follow-up visit will be required 1 week after the overnight study visit.
           Participants will receive information about other alcohol abuse treatment programs.
    

Detailed description: 
      Objective:

      The selective GABAB receptor agonist baclofen has been identified as a possible medication
      able to reduce alcohol craving and intake in alcohol dependent individuals. In keeping with
      several preclinical studies, most of the clinical studies have demonstrated baclofen s
      effects in reducing alcohol craving and intake and promoting alcohol abstinence. However, one
      trial with alcoholics with a low severity of dependence found a robust treatment effect, but
      no differences between baclofen and placebo. The inconsistency of baclofen s effects on
      alcohol drinking among previous treatment trials suggests that different AD individuals may
      respond differently to baclofen. Baclofen has been demonstrated to consistently reduce
      anxiety in alcoholic patients, and analyses of positive vs. null findings with baclofen
      suggest that alcoholic patients with higher levels of anxiety at baseline may represent a
      sub-population particularly responsive to baclofen treatment. Therefore, this study will
      systematically test, for the first time, the specific role of baclofen on alcohol-related
      outcomes in alcoholic individuals with high anxiety levels. Furthermore, the biobehavioral
      mechanisms by which baclofen reduces drinking are not well characterized. A human laboratory
      pilot study conducted at Brown University with non-treatment seeking alcohol-dependent
      individuals suggests that baclofen reduces alcohol consumption both in the naturalistic
      environment as well as in a well-controlled lab setting (using an alcohol self-administration
      [ASA] paradigm) and that this could be mediated by baclofen s ability to alter
      alcohol-related biphasic effects. An exploratory analysis also revealed that specific genetic
      polymorphisms might moderate baclofen s effects, i.e. DRD4 and 5HTTLPR polymorphisms,
      although the sample of that pilot study was very small to allow one to draft definitive
      conclusions. The present project proposes investigating baclofen using a design similar to
      that used in the previous pilot study (thus, an already validated paradigm), thus
      representing not only the first study testing baclofen in alcoholic individuals with high
      anxiety levels, but also the first study investigating baclofen s biobehavioral mechanisms in
      such a population for which baclofen may hypothetically show a very robust effect.

      Study population:

      Non-treatment seeking alcohol-dependent males and females with high anxiety levels.

      Design:

      The experimental design is a between-subject randomized double-blind controlled study. The
      medication conditions baclofen t.i.d. or placebo represent the between subjects factor. Each
      participant will be randomly assigned to one of the two medication conditions and will
      receive eight days of the medication, followed by an alcohol laboratory session on Day 8. The
      alcohol laboratory session will be conducted in a bar-like room in the NIAAA Outpatient
      Clinic of the NIH CRC. The study will be conducted in consecutive phases which will appear
      contiguous to volunteers: (1) a one-week screening period; (2) an 8-day period (+ 1-5 days if
      needed to permit some participants flexibility in scheduling the laboratory session) during
      which participants will take the study medication; (3) an alcohol laboratory session,
      including a cue reactivity (CR) test and an alcohol self-administration (ASA) procedure on
      Day 8 (last day at the target dose); (4) a 3-day period during which participants will
      undergo a dose reduction of the study medication; (5) a 1-week follow-up (including the
      tapering phase).

      Outcome measures:

      Alcohol drinking during the ASA will be measured as the primary outcome. Secondary objectives
      include baclofen s effects on alcohol cue-induced responses (urge to drink, attention to
      cues, blood pressure, heart rate, saliva), on the subjective effects of alcohol and on
      anxiety levels. We will also explore the role of possible moderators of baclofen s effects,
      namely family history of alcoholism, early vs. later onset of alcoholism, pre-treatment
      anxiety levels and genetic moderators (DRD4, 5-HTTPRL). This study does not offer direct
      benefit to participants but is likely to yield generalizable knowledge about the possible
      role of baclofen in treating alcoholic individuals with high anxiety levels. This will
      markedly facilitate the identification of a novel pharmacotherapy, thus facilitating the
      development of novel alcoholism treatments.
    

Intervention name(s): Baclofen; Placebo
Intervention type(s): Drug; Other
Intervention MeSH terms: Baclofen
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: Addiction; Cue-Induced Craving; Craving; Anxiety; Alcohol Consumption