CRF1 Antagonist GSK561679 in Alcoholism
Condition: Alcohol Dependence
MeSH terms: Alcoholism
Study type: Interventional
Phase: Phase 2

Summary: 
      Objective:

      To evaluate GSK561679, an orally available, brain penetrant selective CRH1 antagonist for its
      ability to reduce alcohol craving in recently detoxified alcohol dependent women in response
      to stress or alcohol-associated stimuli.

      Study population:

      Up to 60 anxious, alcohol dependent women, aged 21-65 years will be enrolled to complete the
      study in 50 patients.

      Background:

        -  Anxiety, irritability, anger, and depression can all cause stress that may lead to
           continued drinking in heavy drinkers. One way the brain responds to stress is through a
           protein on brain cells called a CRH receptor. Previous research has shown that the CRH
           receptor is involved in negative emotional states and that chronic alcohol consumption
           increases the activity of CRH receptors in the brain. Medications that block CRH
           receptors can decrease stress-triggered alcohol consumption.

        -  GSK561679, an experimental drug that blocks the CRH receptors, can reduce negative
           emotions such as anxiety and a person s desire for alcohol. By looking at the brain s
           response to stress and the study drug using functional magnetic resonance imaging (fMRI)
           scans, researchers hope to learn whether GSK561679 can be an effective treatment for
           stress-related alcohol abuse.

      Objectives:

      - To evaluate the usefulness of GSK561679 in reducing stress-related alcohol craving in
      alcohol-dependent women.

      Design:

        -  Participants in the study will be enrolled in the standard NIH treatment program for
           alcohol dependence, and will be required to stay at the NIH inpatient treatment unit for
           an additional 31 days.

        -  Participants will receive either the study medication or a placebo to be taken once a
           day in the evening for 4 weeks.

        -  Participants will have the following procedures while on the study medication:

        -  Questionnaires about alcohol craving, depression, and anxiety.

        -  Recordings and responses to personal emotional reactions to stressful, nonstressful, and
           alcohol-related situations, with blood samples taken during the responses.

        -  Regular blood tests to measure stress hormones in the blood.

        -  Speech preparation and presentation (Trier test), along with blood samples, to measure
           stress hormones in the blood.

        -  Sessions to measure responses to alcohol-related cues.

        -  Functional magnetic resonance imaging (fMRI) scans.

        -  Participants will return for follow-up visits 1 week and 1 month after stopping the
           study drug and being discharged from the study.
    

Detailed description: 
      Objective:

      To evaluate GSK561679, an orally available, brain penetrant selective CRH1 antagonist for its
      ability to reduce alcohol craving in recently detoxified alcohol dependent women in response
      to stress or alcohol-associated stimuli.

      Study population:

      Up to 60 anxious, alcohol dependent women, aged 21-65 years will be enrolled to complete the
      study in 50 patients.

      Design:

      Subjects will be inpatients and enter the present protocol once withdrawal treatment, if
      needed, is completed. One week of single blind placebo will be followed by randomized double
      blind treatment with active medication or placebo for approximately 3 weeks. Spontaneous
      craving for alcohol and ratings of psychopathology will be obtained twice weekly throughout
      the study. During the placebo lead-in week, a diurnal cortisol curve will be obtained, and a
      baseline dexamethasone-CRH test may be carried out. These measures will be repeated after
      10-14 days of randomized treatment. Around this time, craving responses will also be assessed
      in a challenge session that combines a social stressor and exposure to physical alcohol cues.
      During the final week, three sessions of guided imagery will be carried out, on separate days
      and in a counter-balanced order, exposing the subject to personalized stress-, alcohol- or
      neutral condition associated stimuli. An fMRI session will be carried out last. Subjects will
      remain hospitalized throughout the study, and will remain on the unit for a 3 day
      post-medication monitoring period.

      Outcome measures:

      The primary outcome will be craving for alcohol on guided imagery challenge sessions.
      Secondary outcomes will include craving as measured in the combined social stress alcohol cue
      challenge session, spontaneous craving and psychopathology ratings repeatedly measured on the
      inpatient unit over time. Exploratory blood biomarkers and brain responses to positive and
      negative affective stimuli on the fMRI session will also be obtained.
    

Intervention name(s): GSK561679; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Verucerfont is a corticotropin releasing hormone receptor 1 (CRF1) antagonist.; Placebo is an inactive tablet design to look exactly like GSK561679
Other intervention name(s): Verucerfont
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Addiction; Alcohol Dependence; Anxiety; CRH Antagonist; Stress Induced Craving