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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03479086
Recruitment Status : Unknown
Verified May 2018 by Professor Paul Haber, South West Sydney Local Health District.
Recruitment status was:  Recruiting
First Posted : March 27, 2018
Last Update Posted : May 11, 2018
Sponsor:
Collaborators:
National Health and Medical Research Council, Australia
University of Sydney
Information provided by (Responsible Party):
Professor Paul Haber, South West Sydney Local Health District

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.

Condition or disease Intervention/treatment Phase
Alcohol Dependence Drug: Topiramate Drug: Naltrexone Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Defining the Clinical Role of Topiramate in the Treatment of Alcohol Dependence in Australia
Actual Study Start Date : June 20, 2017
Estimated Primary Completion Date : November 1, 2020
Estimated Study Completion Date : November 1, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Topiramate
Topiramate 200mg/day
Drug: Topiramate
200mg/day 100mg b.i.d

Experimental: Naltrexone
Naltrexone 50mg/day
Drug: Naltrexone
50mg/day




Primary Outcome Measures :
  1. Number of heavy drinking days, as measured by the Time Line Follow Back [ Time Frame: Over 12 weeks ]
    Corroborated with Phosphatidylethanol (PEth) levels

  2. Time to relapse, as measured by the Time Line Follow Back [ Time Frame: Over 12 weeks ]
    Corroborated with PEth levels

  3. Time to lapse, as measured by the Time Line Follow Back [ Time Frame: Over 12 weeks ]
    Corroborated with PEth levels

  4. Number of days abstinent, as measured by the Time Line Follow Back [ Time Frame: Over 12 weeks ]
    Corroborated with PEth levels

  5. Number of standard drinks per drinking day, as measured by the Time Line Follow Back [ Time Frame: 12 weeks ]
    Corroborated with PEth levels


Secondary Outcome Measures :
  1. Self report of adverse events [ Time Frame: 12 weeks ]
    as reported by patient during weekly medical management sessions facilitated by the treating doctor.

  2. Penn Alcohol Craving Scale for alcohol craving [ Time Frame: 12 weeks ]
    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.

  3. DASS21 score for presence and/or severity of anxiety [ Time Frame: 12 weeks ]
    as measured by cumulative score of anxiety related questions on the Depression, Anxiety Stress Scale-21 (DASS21).

  4. DASS21 score for presence and/or severity of depression [ Time Frame: 12 weeks ]
    as measured by cumulative score for depression related questions

  5. Insomnia Severity Index for sleep disturbances [ Time Frame: 12 weeks ]
    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

  6. Blood glucose test for diabetes [ Time Frame: 12 weeks ]
    as measured by fasting blood glucose levels in blood

  7. Liver function tests for clinical markers of liver injury [ Time Frame: 12 weeks ]
    as measured by levels of liver enzymes, Alanine Transaminase (ALT), Alkaline Phosphatase (ALP) and Aspartate Transaminase (AST) in blood

  8. Body Mass Index [ Time Frame: 12 weeks ]
    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.

  9. Number of cigarettes smoked daily, as measured by Time Line Follow Back [ Time Frame: 12 weeks ]
  10. Self report of daily measures of expectancies, confidence and drinking [ Time Frame: 12 weeks ]
    as measured using a scale of the likelihood of having a good time and feeling more relaxed if alcohol was consumed.


Other Outcome Measures:
  1. The moderating effect of the OPRM1 polymorphism in response to naltrexone, as measured by number of heavy drinking days [ Time Frame: 12 weeks ]
  2. Cost-effectiveness of topiramate versus naltrexone, as measured by Disability-Adjusted Life Years (DALYs) [ Time Frame: 12 weeks ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03479086


Contacts
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Contact: Kirsten Morley, PhD 95153636 kirsten.morley@sydney.edu.au

Locations
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Australia, New South Wales
Drug Health Services, Royal Prince Alfred Hospital Recruiting
Sydney, New South Wales, Australia, 2050
Contact: Kirsten C Morley, PhD    +61295153636    kirsten.morley@sydney.edu.au   
Contact: Central Intake    95157611    sydneyalcoholtreatmentgroup@gmail.com   
Principal Investigator: Paul Haber, MBBS         
Sponsors and Collaborators
South West Sydney Local Health District
National Health and Medical Research Council, Australia
University of Sydney
Investigators
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Principal Investigator: Paul S Haber, MBBS Sydney Local Health District
Principal Investigator: Andrew Baillie, PhD Macquarie University
Principal Investigator: Kirsten C Morley, PhD University of Sydney
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Professor Paul Haber, Principle Clinical Investigator, South West Sydney Local Health District
ClinicalTrials.gov Identifier: NCT03479086    
Other Study ID Numbers: X16-0231
First Posted: March 27, 2018    Key Record Dates
Last Update Posted: May 11, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Alcoholism
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Topiramate
Naltrexone
Alcohol Deterrents
Narcotic Antagonists
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Anticonvulsants
Hypoglycemic Agents