Corticotropin-Releasing Hormone Receptor 1 (CRH1) Antagonism in Anxious Alcoholics^

Summary

Background:

\- Individuals who are dependent on alcohol often have feelings of anxiety, irritability, anger, and depression. These feelings, as well as stress, may contribute to the risk of relapse and continued drinking. Studies have shown that alcohol consumption increases the activity of certain molecules in the brain known as CRH1 receptors, which are key to producing the body s response to stress, and whose activation generates feelings of anxiety. Researchers are interested in learning whether the experimental drug pexacerfont, which blocks CRH1 receptors and has been studied in individuals with anxiety disorders and depression, can lessen anxiety and craving for alcohol as part of alcohol-dependence treatment.

Objectives:

\- To determine the safety and effectiveness of pexacerfont as a treatment for anxiety-related alcohol craving.

Eligibility:

\- Individuals between 21 and 65 years of age who are alcohol-dependent and have problems with anxiety.

Design:

* This study requires an inpatient admission to the NIH Clinical Center for approximately 1 month, with two additional study visits 1 week and 1 month after discharge from the hospital.
* Participants will be screened with a medical history, physical examination, and blood and urine tests.
* During the inpatient period, participants will have standard treatment for alcohol dependence, including support and interventions from institute staff to address cravings, anxiety, or other psychological problems. Participants will not receive formal psychological treatment or psychiatric medications for anxiety, but will receive training in relaxation techniques.
* Participants will be assigned to take either pexacerfont or placebo for 3 weeks. During this time, participants will have the following procedures:
* Frequent blood tests.
* Rating scales and questionnaires about alcohol cravings and anxiety.
* Dexamethasone suppression test with frequent blood draws to study hormone response to stress.
* Social stress test involving public speaking, followed by blood samples and questionnaires on alcohol craving.
* Cue Reactivity (CR) session to study cravings and responses to alcohol-based cues.
* Functional magnetic resonance imaging scan to evaluate brain activity while taking the medication or placebo.
* Participants will have two follow-up visits for additional blood tests and questionnaires about the effects of the treatment \^.

Conditions

• Alcohol-Related Disorders
• Alcohol Dependence
• Alcoholism
• Anxiety Disorder

Interventions

DRUG

Pexacerfont

300 mg, orally, once/day during week 1, 100 mg, orally, once/day during weeks 2 and 3.

DRUG

Placebo

300 mg, orally, once/day during week 1, 100 mg, orally, once/day during weeks 2 and 3.

Sponsors & Collaborators

• National Institute on Alcohol Abuse and Alcoholism (NIAAA)

  lead NIH

Principal Investigators

• Markus A Heilig, M.D. · National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

21 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2010-10-31

Primary Completion

2014-07-31

Completion

2014-07-31

Countries

• United States

Study Locations