Alcohol DependencePhase 3NCT03479086
Defining the Clinical Role of Topiramate in the Treatment of Alcohol Dependence in Australia
A Phase 3 study testing Topiramate and Naltrexone in people with Alcohol Dependence, run by South West Sydney Local Health District at 1 site in Australia.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Alcohol Dependence
- What is being tested?
- Topiramate and Naltrexone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 180 participants
- Where
- 1 siteAustralia
- Study dates
- 20 Jun 2017to 1 Nov 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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 locations and contacts
1 site in 1 country.
Australia1 site, 1 recruiting
- Recruiting
Drug Health Services, Royal Prince Alfred Hospital
Sydney, New South Wales, 2050
Kirsten C Morley, PhD, +61295153636, kirsten.morley@sydney.edu.au
Central Intake, 95157611, sydneyalcoholtreatmentgroup@gmail.com
About this study
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.
Read the 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
- Being tested
- Topiramate, Naltrexone
- Medical subject headings
- Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TopiramateDrug
200mg/day 100mg b.i.d
NaltrexoneDrug
50mg/day
| Study group | Role | What they receive |
|---|---|---|
| Topiramate | Experimental | Topiramate 200mg/day Receives: Drug: Topiramate |
| Naltrexone | Experimental | Naltrexone 50mg/day Receives: Drug: Naltrexone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of heavy drinking days, as measured by the Time Line Follow Back
Corroborated with Phosphatidylethanol (PEth) levels
Measured: Over 12 weeks
Time to relapse, as measured by the Time Line Follow Back
Corroborated with PEth levels
Measured: Over 12 weeks
Time to lapse, as measured by the Time Line Follow Back
Corroborated with PEth levels
Measured: Over 12 weeks
Number of days abstinent, as measured by the Time Line Follow Back
Corroborated with PEth levels
Measured: Over 12 weeks
Number of standard drinks per drinking day, as measured by the Time Line Follow Back
Corroborated with PEth levels
Measured: 12 weeks
Secondary outcomes (10)
Self report of adverse events
as reported by patient during weekly medical management sessions facilitated by the treating doctor.
Measured: 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.
Measured: 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).
Measured: 12 weeks
DASS21 score for presence and/or severity of depression
as measured by cumulative score for depression related questions
Measured: 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
Measured: 12 weeks
Blood glucose test for diabetes
as measured by fasting blood glucose levels in blood
Measured: 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
Measured: 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.
Measured: 12 weeks
Number of cigarettes smoked daily, as measured by Time Line Follow Back
Measured: 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.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2018
- Study start20 Jun 2017
- Primary completion1 Nov 2020 (estimated)
- Study completion1 Nov 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Alcohol DependenceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 180 participants (estimated)
Sponsor and investigators
- Lead sponsor
- South West Sydney Local Health District
- Sponsor type
- University, hospital or other
- Collaborators
- National Health and Medical Research Council, Australia, University of Sydney
- Responsible party
- Principal investigator, Professor Paul Haber, South West Sydney Local Health District
- Investigators
- Paul S Haber, MBBS, Principal investigator, Sydney Local Health DistrictAndrew Baillie, PhD, Principal investigator, Macquarie UniversityKirsten C Morley, PhD, Principal investigator, University of Sydney
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03479086
- Sponsor's protocol ID
- X16-0231
- Status last verified
- May 2018
- First submitted
- 5 Mar 2018
- Last updated
- 11 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
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.
PubMed 39853353Morley 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.
PubMed 30115121
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Defining the Clinical Role of Topiramate in the Treatment of Alcohol Dependence in Australia
- ClinicalTrials.gov ID
- NCT03479086
- Acronym / sponsor ID
- X16-0231
- Conditions
- Alcohol Dependence
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- South West Sydney Local Health DistrictUniversity, hospital or other
- Collaborators
- National Health and Medical Research Council, Australia, University of Sydney
- Study start
- 20 Jun 2017 (actual)
- Primary completion
- 1 Nov 2020 (estimated)
- Study completion
- 1 Nov 2020 (estimated)
- First posted
- 27 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Topiramate | Experimental | Drug: TopiramateTopiramate 200mg/day |
| Naltrexone | Experimental | Drug: NaltrexoneNaltrexone 50mg/day |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Topiramate200mg/day 100mg b.i.d | Drug | Topiramate |
| Naltrexone50mg/day | Drug | Naltrexone |
Primary outcome
Number of heavy drinking days, as measured by the Time Line Follow Back
Time frame: Over 12 weeks
Corroborated with Phosphatidylethanol (PEth) levels
Time to relapse, as measured by the Time Line Follow Back
Time frame: Over 12 weeks
Corroborated with PEth levels
Time to lapse, as measured by the Time Line Follow Back
Time frame: Over 12 weeks
Corroborated with PEth levels
Number of days abstinent, as measured by the Time Line Follow Back
Time frame: Over 12 weeks
Corroborated with PEth levels
Number of standard drinks per drinking day, as measured by the Time Line Follow Back
Time frame: 12 weeks
Corroborated with PEth levels
10 secondary outcomes
Self report of adverse events
Time frame: 12 weeks
Penn Alcohol Craving Scale for alcohol craving
Time frame: 12 weeks
DASS21 score for presence and/or severity of anxiety
Time frame: 12 weeks
DASS21 score for presence and/or severity of depression
Time frame: 12 weeks
Insomnia Severity Index for sleep disturbances
Time frame: 12 weeks
Blood glucose test for diabetes
Time frame: 12 weeks
Liver function tests for clinical markers of liver injury
Time frame: 12 weeks
Body Mass Index
Time frame: 12 weeks
Number of cigarettes smoked daily, as measured by Time Line Follow Back
Time frame: 12 weeks
Self report of daily measures of expectancies, confidence and drinking
Time frame: 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2018.
- Derived from this study: PubMed 39853353Logge 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.
- Derived from this study: PubMed 30115121Morley 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.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul S Haber, MBBS principal investigator
Sydney Local Health District
Andrew Baillie, PhD principal investigator
Macquarie University
Kirsten C Morley, PhD principal investigator
University of Sydney
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Topiramate and Naltrexone in people with Alcohol Dependence, run by South West Sydney Local Health District at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 11 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kirsten Morley, PhD (95153636, kirsten.morley@sydney.edu.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of heavy drinking days, as measured by the Time Line Follow Back (time frame: Over 12 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03479086, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2018.