Alcoholism Clinical Trial
Official title:
Corticotropin-Releasing Hormone Receptor 1 (CRH1) Antagonism in Anxious Alcoholics
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 ^.
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.
;
Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
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