Clinical trial NCT01227980
Conditions: Alcohol-Related Disorders Alcohol Dependence Alcoholism Anxiety Disorder
Keywords: Addiction Alcohol Alcohol Treatment Alcoholics Alcohol Dependence Anxiety Disorder Alcoholism
Sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Start date: 2010-10-01; Completion date: 2014-07-01
Enrollment: 70 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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 \^.

Detailed description:
OBJECTIVE :

To evaluate pexacerfont, an orally available, brain penetrant selective CRH1 antagonist for its ability to modulate emotional and motivational processes in anxious, recently detoxified alcohol dependent patients.

STUDY POPULATION:

Up to 70 anxious, alcohol dependent subjects, 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. They will undergo interviews for construction of guided imagery scripts during a 3 day pre-treatment phase, after which they will receive randomized double blind treatment with active medication or placebo for 23 days, followed by a 3 day post-treatment inpatient monitoring phase, and two follow-up outpatient visits. While hospitalized, repeated measures of spontaneous craving for alcohol, ratings of psychopathology, and blood chemistry including cortisol will be obtained over this time. During the second week of treatment, craving responses will 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. The final week will also include an fMRI session with emotional and motivational tasks, on a day separate from any guided imagery session. Subjects will remain hospitalized throughout the study, will remain on the unit for a 3 day post-medication monitoring period, and will return for follow up app. 1 and 4 weeks following completion of randomized treatment.

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.

Arms: arm 1: Pexacerfont was given orally as a loading dose of 300 mg/day for 1 week, followed by 100mg/day for 16-20 days arm 2: Oral placebo was given during the 1-week loading dose phase, and during the next 16-20 days
Interventions: intervention 1: Pexacerfont intervention 2: Placebo
Intervention descriptions: intervention 1: 300 mg, orally, once/day during week 1, 100 mg, orally, once/day during weeks 2 and 3. intervention 2: 300 mg, orally, once/day during week 1, 100 mg, orally, once/day during weeks 2 and 3.

Protocol documents: