Clinical trial NCT03479086: Defining the Clinical Role of Topiramate in the Treatment of Alcohol Dependence in Australia
Official title: Defining the Clinical Role of Topiramate in the Treatment of Alcohol Dependence in Australia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Alcohol Dependence
Lead sponsor: South West Sydney Local Health District
Sponsor class: OTHER
Collaborators: name: National Health and Medical Research Council, Australia
name: University of Sydney
First posted: 2018-03-27
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of heavy drinking days, as measured by the Time Line Follow Back
timeFrame: Over 12 weeks
measure: Time to relapse, as measured by the Time Line Follow Back
timeFrame: Over 12 weeks
measure: Time to lapse, as measured by the Time Line Follow Back
timeFrame: Over 12 weeks
measure: Number of days abstinent, as measured by the Time Line Follow Back
timeFrame: Over 12 weeks
measure: Number of standard drinks per drinking day, as measured by the Time Line Follow Back
timeFrame: 12 weeks
Secondary outcomes:
measure: Self report of adverse events
timeFrame: 12 weeks
measure: Penn Alcohol Craving Scale for alcohol craving
timeFrame: 12 weeks
measure: DASS21 score for presence and/or severity of anxiety
timeFrame: 12 weeks
measure: DASS21 score for presence and/or severity of depression
timeFrame: 12 weeks
measure: Insomnia Severity Index for sleep disturbances
timeFrame: 12 weeks
measure: Blood glucose test for diabetes
timeFrame: 12 weeks
measure: Liver function tests for clinical markers of liver injury
timeFrame: 12 weeks
measure: Body Mass Index
timeFrame: 12 weeks
measure: Number of cigarettes smoked daily, as measured by Time Line Follow Back
timeFrame: 12 weeks
measure: Self report of daily measures of expectancies, confidence and drinking
timeFrame: 12 weeks
Other outcomes:
measure: The moderating effect of the OPRM1 polymorphism in response to naltrexone, as measured by number of heavy drinking days
timeFrame: 12 weeks
measure: Cost-effectiveness of topiramate versus naltrexone, as measured by Disability-Adjusted Life Years (DALYs)
timeFrame: 12 weeks
Locations:
city: Sydney
country: Australia
facility: Drug Health Services, Royal Prince Alfred Hospital
state: New South Wales
Study officials:
affiliation: Sydney Local Health District
name: Paul S Haber, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: Macquarie University
name: Andrew Baillie, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Sydney
name: Kirsten C Morley, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.