Medication and Counseling for Controlled Drinking (Project SMART)

Problem drinking gay and bisexual men who try to quit drinking are at risk for relapse to
heavy or problematic drinking because their social lives and social outlets are often
strongly associated with alcohol. These men are most receptive to interventions focused on
moderation of drinking rather than abstinence. However moderation-oriented cognitive-behavior
therapy (CBT) and naltrexone (NTX) are both well established treatments for problem drinkers
who wish to moderate, rather than stop, drinking. Research suggests that combining these
treatments may enhance their efficacy.

This study combines moderation-oriented CBT with NTX in the treatment of problem drinking gay
and bisexual men, who do not wish to abstain from alcohol, to evaluate their efficacy alone
and in combination. We also propose to utilize new data collection technology, Interactive
Voice Response, to collect data on daily relations among drinking, sexual behavior and
psychological variables thought to mediate treatment response. Our objectives are to evaluate
the efficacy of 12 weeks of randomly assigned treatment, with 100 mg of NTX or placebo,
combined with brief supportive therapy or modified, behavioral self-control therapy
specifically tailored to gay/bisexual men; to evaluate conditional relationships between
heavy drinking and likelihood of HIV risk behavior; and to evaluate daily associations among
mood, craving, self-efficacy, motivation, and drinking. Assessments will include baseline, 3,
6, & 9 month follow-up. A substudy of the treatment trial will be conducted to collect and
bank samples from blood for research aimed at associating naturally occurring differences in
DNA with patient response to NTX, and with potential mediational mechanisms of action of NTX.
Information gathered on genes or gene products may be used in conjunction with data on
clinical and psychological factors obtained as part of the clinical trial to evaluate
relationships among genetic variants, drug effects, and mechanisms of treatment response.
Patients will be asked to give a blood sample at Week 0 of the clinical trial for the purpose
of carrying out genetic research.

Inclusion Criteria:

- Males 18-65 years old

- Currently sexually active with other men

- Report drinking at levels substantially in excess of established guidelines for
non-hazardous drinking

- Willing to reduce drinking to non-hazardous levels

- English literate (8th grade level)

Exclusion Criteria:

- Current physical disease or condition making participant inappropriate for a
medication trial, including total bilirubin elevation >110%, AST or ALT elevations
>300%.

- History of serious psychiatric illness (psychotic disorder, bipolar disorder, or
psychiatric illness requiring hospitalization), current psychiatric illness (such as
major depression or post-traumatic stress disorder) that requires treatment but that
is currently untreated, or serious risk of suicidal or violent behavior

- Recent (past three months) initiation of psychotropic medication or psychotherapy, or
recent change in psychotropic medication treatment

- Current DSM-IV diagnosis of drug (other than nicotine) dependence, or lifetime
diagnosis of opioid dependence

- DSM-IV alcohol dependence diagnosis judged clinically severe, history or present
evidence of significant alcohol withdrawal symptoms, or recurrent use of alcohol to
alleviate withdrawal

- Regular use of opioids in the past month

- History of hypersensitivity to NTX

- Considered by study physician not to be suitable for receipt of an investigational
drug

- Likely to require treatment with opiate pain medication during the course of the study