Modulation of Pharmacologically Induced Alcohol Craving in Recently Detoxified Alcoholics

NCT00605904 | Completed Phase 2 Results

• 2 other identifiers: 08005808-AA-0058
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

This study will determine if acamprosate, a drug approved to treat alcoholism, decreases alcohol cravings in alcohol-dependent subjects following infusions of yohimbine and mCPP. Yohimbine causes anxiety and may provoke a desire for alcohol; mCPP induces a feeling of having had a few drinks, which often creates a desire for more drinks. If acamprosate can prevent a craving following these stimuli, then the effectiveness of new experimental drugs for treating alcoholism can be tested for their ability to block yohimbine or mCPP-induced cravings. This type of investigation would be less expensive and less time-consuming than conducting clinical trials with alcohol-dependent people. People between 21 and 65 years of age who are alcohol-dependent and have been drinking regularly for at least 1 month before entering the study may be eligible to participate. Participants are admitted to the NIH Clinical Center for about 35 days, during which time they are asked to participate in an alcohol treatment program. They may request passes to leave the hospital during the day but must return overnight. Upon return to the hospital, subjects are required to take a breathalyzer test for alcohol and urine screen for drug use. Participants found to have used drugs or consumed alcohol while away from the hospital are terminated from the study. Participants are randomly assigned to take acamprosate or placebo pills three times a day for about 2 weeks. They are then given three intravenous (through a vein) infusions, 5 to 7 days apart, each containing either yohimbine, mCPP or placebo. The drugs are infused for 20 minutes following a 1-hour infusion of saline (salt water). Subjects complete two questionnaires - an alcohol urge questionnaire to assess the desire for alcohol and a PASS rating scale to assess anxiety - several times during the study and during the infusions....

Conditions

Alcoholism

Keywords

Chemical Stressor; Alcoholism; Yohimbine; Acamprosate; Craving

Outcome Measures

Primary Outcomes (3)

• Alcohol Craving Rating in Response to Saline Infusion

  Alcohol craving was measured using the Penn Alcohol Craving Scale (PACS). It is a 5-item self-administered instrument that measures frequency, intensity, and duration of thoughts about drinking, along with ability to resist drinking. There is a single outcome score than ranges from 0 to 30, with 30 being the maximum amount of alcohol craving.

  180 minutes after the start of the infusion

• Alcohol Craving Rating in Response to Meta-Chlorophenylpiperazine

  Alcohol craving was measured using the Penn Alcohol Craving Scale (PACS). It is a 5-item self-administered instrument that measures frequency, intensity, and duration of thoughts about drinking, along with ability to resist drinking. There is a single outcome score than ranges from 0 to 30, with 30 being the maximum amount of alcohol craving.

  180 minutes after the start of the infusion

• Alcohol Craving Rating in Response to Yohimbine Infusion

  Alcohol craving was measured using the Penn Alcohol Craving Scale (PACS). It is a 5-item self-administered instrument that measures frequency, intensity, and duration of thoughts about drinking, along with ability to resist drinking. There is a single outcome score than ranges from 0 to 30, with 30 being the maximum amount of alcohol craving.

  180 minutes after the start of the infusion

Study Arms (2)

Acamprosate

EXPERIMENTAL

Subjects received 3 tablets of 333mg acamprosate orally, three times daily (total dose of 999 mg) for a minimum of 2 weeks.

Drug: Acamprosate; Drug: Yohimbine; Drug: mCPP; Drug: Saline

Placebo

PLACEBO COMPARATOR

Subjects received 3 tablets of placebo orally, three times daily, for a minimum of 2 weeks.

Drug: Yohimbine; Drug: mCPP; Drug: Saline

Interventions

Acamprosate DRUG

orally administered tablet, 333mg, three times daily for a minimum of 2 weeks (14 days)

Also known as: Campral

Acamprosate

Yohimbine DRUG

Intravenous infusion of yohimbine (0.4 mg/kg) administered once over 10 minutes

Also known as: Yohimbe, Yocon, Yohimex, Aphrodyne

Acamprosate; Placebo

mCPP DRUG

Intravenous infusion of mCPP (0.05 mg/kg) over 10 minutes, two times, for a total of 0.1 mg/kg

Also known as: 3-CPP, CPP

Acamprosate; Placebo

Saline DRUG

Intravenous infusion of 0.9% sodium chloride solution over 10 minutes, three times during the study (2 times for the "Saline Infusion" milestone, and one time immediately following the "Yohimbine Infusion" milestone)

Also known as: Normal Saline Flush, Sodium Chloride

Acamprosate; 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:

• Subjects will be 60 recently detoxified alcoholics according to the following criteria:
• DSM-IV diagnosis of alcohol dependence on SCID, alcohol problems as primary complaint among substance use disorder, and alcohol use within the last month.
• Spielberger trait anxiety (21) score greater than 39
• Age 21-65
• Females of childbearing potential must agree to use a reliable method of birth control during the study. Reliable methods of birth control include oral contraceptives or Norplant(Registered Trademark); barrier methods such as diaphragms with contraceptive jelly, cervical caps with contraceptive jelly, condoms with contraceptive foam, or intrauterine devices; a partner with a vasectomy; or abstinence from intercourse.

You may not qualify if:

• People who present with significant medical problems which in the assessment of the Lead Associate Investigator contraindicate administration of any of the study drugs. Examples are patients requiring intensive medical or diagnostic management, such as uncontrolled hypertension, serious GI bleeding, major organ or body system dysfunction such as decompensated liver disease, renal failure, myocardial ischemia, congestive heart failure or cerebrovascular disease, major endocrine problems such as uncontrolled diabetes, pancreatic or thyroid disease, or glaucoma.
• People who are infected with the Human Immunodeficiency Virus (HIV).
• People with the following specific neuro-psychiatric disorders: any psychotic disorder including schizophrenia; bipolar affective disorder; or panic disorder.
• People with any other condition that impairs judgment or cognitive function to an extent that precludes them from providing informed consent or complying with treatment (incompetent individuals); or that requires management with pharmacotherapy that would make the subject ineligible for participation.
• Contraindications for acamprosate (previously exhibited hypersensitivity to acamprosate calcium or any of its components; or severe renal impairment, manifested as creatinine clearance of 30 mL/min or less.
• Contraindications for yohimbine or mCPP, such as liver or renal disease; chronic inflammation of the sexual organs or prostate gland; history of gastric and duodenal ulcers; glaucoma; hypersensitivity to yohimbine or mCPP
• People who are unlikely or unable to complete the treatment program because they become, or are likely to be, incarcerated while on the protocol.
• People who are required to receive treatment by a court of law or who are involuntarily committed to treatment.
• Pregnancy or lactation (negative pregnancy test required)
• Regular use of psychotropic medication, physician prescribed or purchased over the counter (e.g. antidepressant, lithium, antipsychotic, anxiolytic, antiepileptic, nasal decongestants in tablet form) or blood pressure medication (e.g. beta-blockers, calcium antagonists, ACE-inhibitors or AT1 antagonists) within the last 4 weeks, with the exception of benzodiazepines administered within the NIAAA program as part of alcohol withdrawal treatment. Specifically, no subject will be taken off psychoactive medications for the purpose of enrollment in this protocol.

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

• Heilig M, Koob GF. A key role for corticotropin-releasing factor in alcohol dependence. Trends Neurosci. 2007 Aug;30(8):399-406. doi: 10.1016/j.tins.2007.06.006. Epub 2007 Jul 16.

  PMID: 17629579 BACKGROUND

• Bohn MJ, Krahn DD, Staehler BA. Development and initial validation of a measure of drinking urges in abstinent alcoholics. Alcohol Clin Exp Res. 1995 Jun;19(3):600-6. doi: 10.1111/j.1530-0277.1995.tb01554.x.

  PMID: 7573780 BACKGROUND

MeSH Terms

Conditions

Alcoholism

Interventions

Acamprosate; Yohimbine; 6-chloro-2-(1-piperazinyl)pyrazine; Sodium Chloride

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Taurine; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Markus Heilig
• Organization: NIAAA, NIH

mheilig@mail.nih.gov

301.435.9386

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Director, NIAAA

Study Record Dates

• First Submitted: January 30, 2008
• First Posted: January 31, 2008
• Study Start: January 1, 2008
• Primary Completion: September 1, 2010
• Study Completion: March 1, 2011
• Last Updated: July 3, 2012
• Results First Posted: July 3, 2012

Record last verified: 2012-05

Locations

US (1)