CRF1 Antagonist GSK561679 in Alcoholism

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.

Conditions

• Alcohol Dependence

Interventions

DRUG

GSK561679

Verucerfont is a corticotropin releasing hormone receptor 1 (CRF1) antagonist.

DRUG

Placebo

Placebo is an inactive tablet design to look exactly like GSK561679

Sponsors & Collaborators

• National Institute on Alcohol Abuse and Alcoholism (NIAAA)

  lead NIH

Principal Investigators

• Lorenzo Leggio, M.D. · National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

21 Years

Max Age

65 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2010-01-31

Primary Completion

2015-09-30

Completion

2015-09-30

Countries

• United States

Study Locations