Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Health and Medical Research Council, Australia | OTHER |
| University of Sydney | OTHER |
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Topiramate | Experimental | Topiramate 200mg/day |
|
| Naltrexone | Experimental | Naltrexone 50mg/day |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Topiramate | Drug | 200mg/day 100mg b.i.d |
| |
| Naltrexone |
| Measure | Description | Time Frame |
|---|---|---|
| Number of heavy drinking days, as measured by the Time Line Follow Back | Corroborated with Phosphatidylethanol (PEth) levels | Over 12 weeks |
| Time to relapse, as measured by the Time Line Follow Back | Corroborated with PEth levels | Over 12 weeks |
| Time to lapse, as measured by the Time Line Follow Back | Corroborated with PEth levels | Over 12 weeks |
| Number of days abstinent, as measured by the Time Line Follow Back | Corroborated with PEth levels | Over 12 weeks |
| Number of standard drinks per drinking day, as measured by the Time Line Follow Back | Corroborated with PEth levels | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Self report of adverse events | as reported by patient during weekly medical management sessions facilitated by the treating doctor. | 12 weeks |
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| The moderating effect of the OPRM1 polymorphism in response to naltrexone, as measured by number of heavy drinking days | 12 weeks | |
| Cost-effectiveness of topiramate versus naltrexone, as measured by Disability-Adjusted Life Years (DALYs) | 12 weeks |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Kirsten Morley, PhD | Contact | 95153636 | kirsten.morley@sydney.edu.au |
| Name | Affiliation | Role |
|---|---|---|
| Paul S Haber, MBBS | Sydney Local Health District | Principal Investigator |
| Andrew Baillie, PhD | Macquarie University | Principal Investigator |
| Kirsten C Morley, PhD |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Drug Health Services, Royal Prince Alfred Hospital | Recruiting | Sydney | New South Wales | 2050 | Australia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39853353 | Derived | 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. | |
| 30115121 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D000437 | Alcoholism |
| ID | Term |
|---|---|
| D019973 | Alcohol-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077236 | Topiramate |
| D009271 | Naltrexone |
| ID | Term |
|---|---|
| D005632 | Fructose |
| D006601 | Hexoses |
| D009005 | Monosaccharides |
| D000073893 | Sugars |
| D002241 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Drug |
50mg/day |
|
| 12 weeks |
| 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 |
| DASS21 score for presence and/or severity of depression | as measured by cumulative score for depression related questions | 12 weeks |
| 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 |
| Blood glucose test for diabetes | as measured by fasting blood glucose levels in blood | 12 weeks |
| 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 |
| 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 |
| Number of cigarettes smoked daily, as measured by Time Line Follow Back | 12 weeks |
| 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 |
| University of Sydney |
| Principal Investigator |
| 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. |
| Carbohydrates |
| D007661 | Ketoses |
| D009270 | Naloxone |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |