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

NCT01227980 | Completed Phase 2 Results

• 2 other identifiers: 11001011-AA-0010
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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 \^.

Conditions

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

Keywords

Addiction; Alcohol; Alcohol Treatment; Alcoholics; Alcohol Dependence; Anxiety Disorder; Alcoholism

Outcome Measures

Primary Outcomes (16)

• Alcohol Craving in Response to the Alcohol Cue Script

  Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

  15 minutes prior to the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period

• Alcohol Craving in Response to the Alcohol Cue Script

  Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

  5 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period

• Alcohol Craving in Response to the Alcohol Cue Script

  Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

  15 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period

• Alcohol Craving in Response to the Alcohol Cue Script

  Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

  30 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period

• Alcohol Craving in Response to the Alcohol Cue Script

  Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

  45 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period

• Alcohol Craving in Response to the Alcohol Cue Script

  Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

  60 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period

• Alcohol Craving in Response to the Alcohol Cue Script

  Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

  75 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period

• Alcohol Craving in Response to the Alcohol Cue Script

  Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

  90 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period

• Alcohol Craving in Response to the Stress Script

  Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

  15 minutes prior to the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period

• Alcohol Craving in Response to the Stress Script

  Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

  5 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period

• Alcohol Craving in Response to the Stress Script

  Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

  15 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period

• Alcohol Craving in Response to the Stress Script

  Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

  30 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period

• Alcohol Craving in Response to the Stress Script

  Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

  45 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period

• Alcohol Craving in Response to the Stress Script

  Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

  60 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period

• Alcohol Craving in Response to the Stress Script

  Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

  75 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period

• Alcohol Craving in Response to the Stress Script

  Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).

  90 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period

Study Arms (2)

Pexacerfont

ACTIVE COMPARATOR

Pexacerfont was given orally as a loading dose of 300 mg/day for 1 week, followed by 100mg/day for 16-20 days

Drug: Pexacerfont

Placebo

PLACEBO COMPARATOR

Oral placebo was given during the 1-week loading dose phase, and during the next 16-20 days

Drug: Placebo

Interventions

Pexacerfont DRUG

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

Pexacerfont

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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
• Past or present diagnosis of schizophrenia, bipolar disease, or any psychotic disorder other than one determined to be substance induced; past or present diagnosis of dementia, or any other disorder which has led to a clinically significant cognitive impairment; any other psychiatric condition which at the present time requires, or in the past month has required pharmacological intervention other than standard withdrawal treatment as described in the NIAAA Assessment and Treatment Protocol (#05-AA-0121).
• A personality disorder which, in the investigator s judgment could lead to non-compliance with study procedures.

Sponsors & Collaborators

• National Institute on Alcohol Abuse and Alcoholism (NIAAA): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Heilig M, Egli M. Pharmacological treatment of alcohol dependence: target symptoms and target mechanisms. Pharmacol Ther. 2006 Sep;111(3):855-76. doi: 10.1016/j.pharmthera.2006.02.001. Epub 2006 Mar 20.

  PMID: 16545872 BACKGROUND

• Epstein DH, Preston KL, Stewart J, Shaham Y. Toward a model of drug relapse: an assessment of the validity of the reinstatement procedure. Psychopharmacology (Berl). 2006 Nov;189(1):1-16. doi: 10.1007/s00213-006-0529-6. Epub 2006 Sep 22.

  PMID: 17019567 BACKGROUND

• Anton RF, Moak DH, Latham PK. The obsessive compulsive drinking scale: A new method of assessing outcome in alcoholism treatment studies. Arch Gen Psychiatry. 1996 Mar;53(3):225-31. doi: 10.1001/archpsyc.1996.01830030047008.

  PMID: 8611059 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Alcohol-Related Disorders; Alcoholism; Anxiety Disorders; Behavior, Addictive

Interventions

pexacerfont

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Compulsive Behavior; Impulsive Behavior; Behavior

Results Point of Contact

• Title: Melanie Schwandt
• Organization: National Institute on Alcohol Abuse and Alcoholism

melanies@mail.nih.gov

301-451-6960

Study Officials

• Markus A Heilig, M.D.

  National Institute on Alcohol Abuse and Alcoholism (NIAAA)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2010
• First Posted: October 25, 2010
• Study Start: October 1, 2010
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: February 2, 2016
• Results First Posted: December 10, 2015

Record last verified: 2015-12

Locations

US (1)