Phase 2 N=70 Randomized Double-blind Treatment

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

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

Bottom Line

View on ClinicalTrials.gov: NCT01227980 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Dec 2015

Primary outcome: Primary: Alcohol Craving in Response to the Alcohol Cue Script — 12.7; 10.7 Units on a scale

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Pexacerfont (Drug); Placebo (Drug)
Age: Adult, Older Adult · 21+ yrs
Sex: All
Sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Primary completion: Jul 2014

Outcome Measures

Outcome	Result	p-value
PRIMARY Alcohol Craving in Response to the Alcohol Cue Script	13.7; 11.7	—
PRIMARY Alcohol Craving in Response to the Alcohol Cue Script	13.7; 11.7	—
PRIMARY Alcohol Craving in Response to the Alcohol Cue Script	13.7; 11.7	—
PRIMARY Alcohol Craving in Response to the Alcohol Cue Script	13.7; 11.7	—
PRIMARY Alcohol Craving in Response to the Alcohol Cue Script	13.7; 11.7	—
PRIMARY Alcohol Craving in Response to the Alcohol Cue Script	13.7; 11.7	—
PRIMARY Alcohol Craving in Response to the Alcohol Cue Script	13.7; 11.7	—
PRIMARY Alcohol Craving in Response to the Alcohol Cue Script	13.7; 11.7	—
PRIMARY Alcohol Craving in Response to the Stress Script	14.6; 11.2	—
PRIMARY Alcohol Craving in Response to the Stress Script	14.6; 11.2	—
PRIMARY Alcohol Craving in Response to the Stress Script	14.6; 11.2	—
PRIMARY Alcohol Craving in Response to the Stress Script	14.6; 11.2	—
PRIMARY Alcohol Craving in Response to the Stress Script	14.6; 11.2	—
PRIMARY Alcohol Craving in Response to the Stress Script	14.6; 11.2	—
PRIMARY Alcohol Craving in Response to the Stress Script	14.6; 11.2	—
PRIMARY Alcohol Craving in Response to the Stress Script	14.6; 11.2	—

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 ^.

Eligibility Criteria

INCLUSION CRITERIA:
Signed written informed consent:

a. Patients must be competent to understand the nature of the study, sign the informed consent prior to any study-related procedures, agree to comply with the prescribed dosage regimens, agree to remain hospitalized at the NIH Clinical Center throughout the duration of the study and to return for follow-up visits as specified, and agree to communicate to study personnel about adverse events and concomitant medication use.

Target population:
DSM-IV diagnosis of alcohol dependence on SCID interview,
alcohol problems as primary complaint among substance use disorders,
alcohol use within the last month.
Spielberger trait anxiety inventory score > 39.
Right-handedness
Age and sex:
Men and women, ages 21 65 years.
Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) prior to enrollment, and agree to using an adequate method of contraception to avoid pregnancy for a period of 6 months beginning from first dose of randomized treatment. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal. Adequate methods of contraception are practicing complete abstinence from intercourse for two weeks prior to administration of study drug; having a male sexual partner(s) who is surgically sterilized (vasectomy with documentation of azoospermia) prior to inclusion; having a sexual partner(s) who is/are exclusively female; using oral contraceptives (either combined or progestogen only) with single-barrier method of contraception consisting of spermicide and condom or diaphragm; using double-barrier contraception, specifically, a condom plus spermicide and a female diaphragm or cervical cap; using an approved intrauterine device (IUD) with established efficacy.
Men, unless surgically sterilized (vasectomy with documentation of azoospermia), must agree to practicing abstinence or using barrier contraception, and not donate sperm, for a period of 6 months beginning from first dose of randomized treatment.

EXCLUSION CRITERIA

General:
Investigator site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted.
Employees of Bristol-Meyers Squibb (BMS) or immediate family of BMS employees.
Subjects with current participation in another clinical study in which the subject is or will be exposed to an investigational or non investigational drug or device; participation in a clinical study for an illness unrelated to alcohol use within the preceding month; or any previous participation in a trial involving pexacerfont or closely related compounds.
Inability or unwillingness to participate in an MR scan, including presence of ferromagnetic metallic objects in the body, or pronounced claustrophobia
Any medical or psychiatric condition or laboratory finding that, in the judgment of the investigator could adversely affect subject safety or study integrity.
Subjects who are unlikely or unable to complete this study because of impending or likely incarceration while on the protocol.
Subjects who are required to receive treatment by a court of law or involuntarily committed to treatment.
Sex and reproductive status:
Inability or unwillingness to practice contraception as described above
Women who are pregnant, breastfeeding, or planning to become pregnant within 6 months from the administration of first study drug dose.
Men who are planning to father a child within 6 months from the

administration of the first study drug dose

Exclusionary psychiatric conditions:
Past or present diagnosis of schizophrenia, bipolar disease, or any psychotic disorder other than one

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01227980). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.