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

NCT ID: NCT03479086

Last Updated: 2018-05-11

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-20
• Study Completion Date: 2020-11-01

Brief Summary

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.

Detailed 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.

Conditions

Alcohol Dependence

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Topiramate

Topiramate 200mg/day

Group Type: EXPERIMENTAL

Topiramate

Intervention Type: DRUG

200mg/day 100mg b.i.d

Naltrexone

Naltrexone 50mg/day

Group Type: EXPERIMENTAL

Naltrexone

Intervention Type: DRUG

50mg/day

Interventions

Topiramate

200mg/day 100mg b.i.d

Intervention Type: DRUG

Naltrexone

50mg/day

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Health and Medical Research Council, Australia

OTHER

Sponsor Role: collaborator

University of Sydney

OTHER

Sponsor Role: collaborator

South West Sydney Local Health District

OTHER

Sponsor Role: lead

Responsible Party

Professor Paul Haber

Principle Clinical Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Paul S Haber, MBBS

Role: PRINCIPAL_INVESTIGATOR

Sydney Local Health District

Andrew Baillie, PhD

Role: PRINCIPAL_INVESTIGATOR

Macquarie University

Kirsten C Morley, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Sydney

Locations

Drug Health Services, Royal Prince Alfred Hospital

Sydney, New South Wales, Australia

Site Status: RECRUITING

Countries

Australia

Central Contacts

Kirsten Morley, PhD

Role: CONTACT

kirsten.morley@sydney.edu.au

95153636

Facility Contacts

Kirsten C Morley, PhD

Role: primary

kirsten.morley@sydney.edu.au

+61295153636

Central Intake

Role: backup

sydneyalcoholtreatmentgroup@gmail.com

95157611

References

Logge WB, Haber PS, Hurzeler T, Gallagher H, Kranzler H, Morley KC. Neural cue reactivity and intrinsic functional connectivity in individuals with alcohol use disorder following treatment with topiramate or naltrexone. Psychopharmacology (Berl). 2025 Jul;242(7):1641-1652. doi: 10.1007/s00213-025-06745-7. Epub 2025 Jan 24.

Reference Type: DERIVED

PMID: 39853353 (View on PubMed)

Morley KC, Kranzler HR, Luquin N, Baillie A, Shanahan M, Trent R, Teesson M, Haber PS. Topiramate versus naltrexone for alcohol use disorder: study protocol for a genotype-stratified, double-blind randomised controlled trial (TOP study). Trials. 2018 Aug 16;19(1):443. doi: 10.1186/s13063-018-2824-z.

Reference Type: DERIVED

PMID: 30115121 (View on PubMed)

Other Identifiers

X16-0231

Identifier Type: -

Identifier Source: org_study_id