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

Alcohol Dependence Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03479086
• Other study ID #: X16-0231
• Status: Recruiting
• Phase: Phase 3
• Start date: June 20, 2017
• Est. completion date: November 1, 2020

Study information

• Verified date: May 2018
• Source: South West Sydney Local Health District
• Contact: Kirsten Morley, PhD
• Phone: 95153636
• Email: kirsten.morley[@]sydney.edu.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: November 1, 2020
• Est. primary completion date: November 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Alcohol Dependence
• Alcoholism

Intervention

Drug:
• Topiramate
200mg/day 100mg b.i.d
• Naltrexone
50mg/day

Locations

Country	Name	City	State
Australia	Drug Health Services, Royal Prince Alfred Hospital	Sydney	New South Wales

Sponsors (3)

Lead Sponsor	Collaborator
South West Sydney Local Health District	National Health and Medical Research Council, Australia, University of Sydney

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The moderating effect of the OPRM1 polymorphism in response to naltrexone, as measured by number of heavy drinking days		12 weeks
Other	Cost-effectiveness of topiramate versus naltrexone, as measured by Disability-Adjusted Life Years (DALYs)		12 weeks
Primary	Number of heavy drinking days, as measured by the Time Line Follow Back	Corroborated with Phosphatidylethanol (PEth) levels	Over 12 weeks
Primary	Time to relapse, as measured by the Time Line Follow Back	Corroborated with PEth levels	Over 12 weeks
Primary	Time to lapse, as measured by the Time Line Follow Back	Corroborated with PEth levels	Over 12 weeks
Primary	Number of days abstinent, as measured by the Time Line Follow Back	Corroborated with PEth levels	Over 12 weeks
Primary	Number of standard drinks per drinking day, as measured by the Time Line Follow Back	Corroborated with PEth levels	12 weeks
Secondary	Self report of adverse events	as reported by patient during weekly medical management sessions facilitated by the treating doctor.	12 weeks
Secondary	Penn Alcohol Craving Scale for alcohol craving	as measured by amount of time spent thinking and craving for alcohol, difficulty in resisting consumption of alcohol if present and hypothetical pleasure associated with consumption of alcohol.	12 weeks
Secondary	DASS21 score for presence and/or severity of anxiety	as measured by cumulative score of anxiety related questions on the Depression, Anxiety Stress Scale-21 (DASS21).	12 weeks
Secondary	DASS21 score for presence and/or severity of depression	as measured by cumulative score for depression related questions	12 weeks
Secondary	Insomnia Severity Index for sleep disturbances	as measured by cumulative score of satisfaction with current sleep patterns and extent to which sleep disturbances interfere and impair with every day activities and daily functioning	12 weeks
Secondary	Blood glucose test for diabetes	as measured by fasting blood glucose levels in blood	12 weeks
Secondary	Liver function tests for clinical markers of liver injury	as measured by levels of liver enzymes, Alanine Transaminase (ALT), Alkaline Phosphatase (ALP) and Aspartate Transaminase (AST) in blood	12 weeks
Secondary	Body Mass Index	as measured by weight in kilograms (kg) and height in metres (m). These two measurements will be combined together to report BMI in kg/m^2.	12 weeks
Secondary	Number of cigarettes smoked daily, as measured by Time Line Follow Back		12 weeks
Secondary	Self report of daily measures of expectancies, confidence and drinking	as measured using a scale of the likelihood of having a good time and feeling more relaxed if alcohol was consumed.	12 weeks