Aripiprazole and Topiramate on Free-Choice Alcohol Use

Summary

The current study investigates the effects of two potential alcohol treatment medications on drinking in a laboratory setting. Aripiprazole (APZ), effects dopamine and serotonin receptors with fewer limiting side effects seen with other atypical antipsychotics. Topiramate (TPMT), an antiepileptic, affects glutamate and GABA-A receptors and shows promise in reducing heavy drinking. Few studies have used two medications with such a diverse combination of actions to examine a potential synergistic effect on reducing alcohol consumption.

The primary aims are to:

1. determine if APZ and TPMT are each more effective than placebo, and the combination of APZ and TPMT is more effective than either drug alone or placebo, in reducing alcohol use in non-treatment seeking alcohol dependent subjects in a laboratory based alcohol self-administration experiment (ASAE)
2. examine a hypothesized dose-response for three doses of APZ (0, 7.5 mg/d and 15 mg/d) along with three doses of TPMT (0, 100mg/d and 200mg/d)
3. examine the putative mechanisms of action of APZ, TPMT alone and together on craving, subjective stimulation, candidate gene influences and other behavioral effects associated with alcohol consumption
4. establish the safety of giving APZ and TPMT together. Non-treatment seeking, alcohol dependent Participants (N=216) will be recruited from the community and randomly assigned to one of the 9 cells. Subjects drinking and safety is monitored over a 5-week titration to their target dose, leading to an in-laboratory alcohol self administration session, during which clinical and behavioral effects are assessed during access to alcohol. A 1 month follow-up assesses adverse events and drinking.

Conditions

• Alcohol Dependence

Interventions

DRUG

Double Placebo

1 capsule daily

DRUG

Aripiprazole 15, placebo

15 mg Aripiprazole daily plus placebo daily

DRUG

Aripiprazole 7.5, Placebo

Aripiprazole 7.5 mg daily plus Placebo daily

DRUG

Topiramate 100, Placebo

Topiramate 100 mg daily plus Placebo daily

DRUG

Topiramate 200, Placebo

Topiramate 200 mg daily plus Placebo daily

DRUG

Topiramate 100, Aripiprazole 15

Topiramate 100 mg daily plus Aripiprazole 15mg daily

DRUG

Topiramate 100, Aripiprazole 7.5

Topiramate 100 mg daily plus Aripiprazole 7.5mg daily

DRUG

Topiramate 100, Aripiprazole 15mg

Topiramate 100 mg daily plus Aripiprazole 15mg daily

DRUG

Topiramate 200, Aripiprazole 7.5mg

Topiramate 200 mg daily plus Aripiprazole 7.5mg daily

DRUG

Topiramate 200, Aripiprazole 15

Topiramate 200mg daily plus Aripiprazole 15mg daily

Sponsors & Collaborators

• Brown University

  collaborator OTHER

• National Institute on Alcohol Abuse and Alcoholism (NIAAA)

  lead NIH

Principal Investigators

• Robert M Swift, MD, PhD · Brown University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2007-09-30

Primary Completion

2015-10-31

Completion

2015-10-31

Countries

• United States

Study Locations