Defining the Clinical Role of Topiramate in the Treatment of Alcohol Dependence in Australia

South West Sydney Local Health District

Status and phase: Unknown; Phase 3

Conditions: Alcohol Dependence

Treatments: Drug: Topiramate; Drug: Naltrexone

Study type: Interventional

Funder types: Other

Identifiers

NCT03479086

X16-0231

Details and patient eligibility

About

To compare the clinical effectiveness, tolerability, and cost-effectiveness of topiramate to active control (naltrexone) on treatment outcomes for alcohol dependence in a double-blind randomised controlled trial.

Full description

Clinicians urgently require new treatment strategies for the treatment of alcohol dependence. Although alcohol use disorders are a leading cause of preventable death in Australia, their treatment is generally not evidence based. The medications currently approved for use in Australia for the management of alcohol dependence have limited efficacy, and existing research does not address the heterogeneity of treatment response.

Targeted personalised medicine addresses this heterogeneity with better medicine selection for patients based on their genotype and clinical comorbidities.

Members of our research team have recently demonstrated findings that support the use of topiramate (TOP) 200 mg/day to reduce heavy drinking and pharmacogenetic findings that implicate the GluK1 receptor subunit in the mechanism of these effects.

This project will evaluate the clinical effectiveness and tolerability of topiramate relative to the active control naltrexone (NTX) in heavy drinkers.

Investigators hypothesise that topiramate treated patients will be better able to achieve a reduction in heavy drinking and predict that, based on prior research, that the effects would be moderated by a single nucleotide polymorphism (rs2832407) in GRIK1.

Research personnel will utilise an innovative prospective pharmacogenetic randomisation approach to a double-blind, randomised, controlled trial.

Individuals will receive 12 weeks of titrated treatment with topiramate (200 mg/day) or naltrexone (50mg/day) and medical management.

Enrollment: 180 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Alcohol Use Disorder according to the Diagnostic and Statistical Manual of Mental Disorders Version V criteria
• Age 18-70
• Average weekly alcohol consumption of >30 standard drinks for men and >25 standard drinks for women, with a weekly average of > 2 heavy drinking days during the month before screening
• Adequate cognition and English language skills to give valid consent and complete research interviews
• Willingness to give written informed consent
• Willingness to provide a blood sample for genotyping
• Written informed consent

Exclusion criteria

• Active major psychological disorder associated with psychosis, significant suicide risk, and signs of impaired cognitive functioning
• Pregnancy or lactation
• Concurrent use of any psychotropic medication other than antidepressants
• Currently taking any tricyclic antidepressant
• Use of antiretroviral dolutegravir
• Any substance dependence other than nicotine
• Opioid abuse, opioid dependence, or on opioid maintenance treatment
• Clinically significant liver disease
• History of nephrolithiasis
• History of glaucoma
• Lack of stable housing and/or contact phone number
• Previous hypersensitivity to TOP or NTX
• Any alcohol pharmacotherapy within the past month

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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180 participants in 2 patient groups

Topiramate

Experimental group

Description:

Topiramate 200mg/day

Treatment:

Drug: Topiramate

Naltrexone

Experimental group

Description:

Naltrexone 50mg/day

Treatment:

Drug: Naltrexone