Modulation of Pharmacologically Induced Alcohol Craving in Recently Detoxified Alcoholics
Condition: Alcoholism
MeSH terms: Alcoholism
Intervention: Acamprosate; Yohimbine; mCPP; Saline
Intervention description: orally administered tablet, 333mg, three times daily for a minimum of 2 weeks (14 days); Intravenous infusion of yohimbine (0.4 mg/kg) administered once over 10 minutes; Intravenous infusion of mCPP (0.05 mg/kg) over 10 minutes, two times, for a total of 0.1 mg/kg; 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)
Intervention MeSH terms: Acamprosate; Yohimbine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 37.0
Sex: All
Minimum age: 21 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Chemical Stressor; Alcoholism; Yohimbine; Acamprosate; Craving

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....
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        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.

        EXCLUSION CRITERIA:

          -  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.