Pharmacogenetic Response to Naltrexone For Alcohol Dependence
Condition: Alcohol Dependence
MeSH terms: Alcoholism
Intervention: naltrexone; Placebo
Intervention description: 50mg/day; Placebo
Intervention MeSH terms: Naltrexone
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 221.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The aims of the study are to test for treatment outcome differences in alcohol dependent
      subjects randomly assigned to 12 weeks of treatment with NTX (50mg/day) or placebo among
      those with one or two copies of the Asp40 allele of the mu-opioid receptor compared to those
      homozygous for the Asn40 allele. Thus, the design of the study is a 2X2 cell double-blind
      randomization to NTX or placebo stratified by genotype. To meet these aims, 150 alcohol
      dependent outpatients with one or two copies of the Asp40 variant of the mu-opioid receptor
      and 190 subjects homozygous for the Asn40 variant will be recruited across the four
      participating sites.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Participant is male or female, 18 years of age or older, and of European or Asian
             descent.

          2. Participant has a current DSM-IV diagnosis of alcohol dependence using the SCID/MINI.

          3. The participant has signed a witnessed informed consent form.

          4. Participant meets the following drinking criteria as measured by the Timeline Follow
             Back (TLFB): a. Drinks at least an average of 21 drinks/wk in the 60-day period prior
             to intake and b. Has 2 or more days of heavy drinking (defined as 5 or more drinks per
             day in males, 4 or more in females) in this same pre-treatment period.

          5. Participant has at least 48 hours of abstinence, as determined by subject report and
             breathalyzer measure immediately prior to randomization.

          6. Participant scores below 8 on the Clinical Inventory of Withdrawal from Alcohol (CIWA)
             prior to starting Naltrexone.

          7. Participant has adequate vision, hearing and ability to communicate to allow study
             participation.

          8. Participant is able to speak, print and understand English.

        Exclusion Criteria:

          1. Participant meets DSM-IV criteria for dependence on any substance other than alcohol
             or nicotine in the last 6 months.

          2. Participant has tested positive on the urine drug screen for opioids, benzodiazepines,
             or cocaine at the screening visit. Presence of THC is allowable.

          3. Participant has a current or lifetime DSM-IV diagnosis of bipolar affective disorder,
             schizophrenia, or any psychotic disorder.

          4. Participant has presence of unstable or serious medical illness such as a recent
             stroke, idiopathic seizure disorder, or cardiac disease.

          5. Participant has severe liver disease (SGPT (ALT) or SGOT (AST) of at least 3 times
             normal value at the time of randomization or an elevated Total Bilirubin level without
             evidence of Gilbert's Syndrome.

          6. Participant has taken any psychotropic medications (including disulfiram) regularly
             within the last seven days (14 for fluoxetine) prior to randomization or needs
             immediate treatment with a psychotropic medication (antidepressant, antipsychotic,
             benzodiazepine, or mood stabilizing medication). EXCEPTIONS: Zolpidem and ramelteon
             used sparingly if necessary for sleep; Oxazepam for alcohol detoxification; Seizure
             disorder medications.

          7. Participant is over the age of 64 and has evidence of severe cognitive impairment as
             evidenced by a Mini-mental status exam (MMSE) score < 24.

          8. Participant meets DSM-IV criteria for current major depression (non-substance
             induced), PTSD, or panic disorder.

          9. Participant has suicidal or homicidal ideation necessitating inpatient
             hospitalization.

         10. Participant is a pre-menopausal female who is pregnant, nursing, or not using a
             reliable method of contraception.

         11. Participant is over age 64 and has evidence of severe cognitive impairment as
             evidenced by a Mini-mental status exam (MMSE) score less than 20.12. Participant is of
             African descent.