Evidence map›Paper›PMID 30115121›Full record

Trial reportTrials2018

Topiramate versus naltrexone for alcohol use disorder: study protocol for a genotype-stratified, double-blind randomised controlled trial (TOP study).

Kirsten C Morley, Henry R Kranzler, Natasha Luquin, Andrew Baillie, Marian Shanahan, Ronald Trent, Maree Teesson, Paul S Haber

Registry-linked trialOpen access · goldAbstract readComparative StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Trials, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03479086 (Defining the Clinical Role of Topiramate in the Treatment of Alcohol Dependence in Australia), which is not on this map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.9field-weighted citation impact, top 31% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03479086 phase3unknown statusnot on this map

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

TypeinterventionalSponsorSouth West Sydney Local Health DistrictRan2017 to 2020Enrolled180ConditionsAlcohol DependenceArmsTopiramate, Naltrexone
3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 12 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Pharmacogenetics of alcohol use disorder treatments: an update.Expert opinion on drug metabolism & toxicology · 2019
    Review
  4. Pharmacogenetics of alcohol addiction: current perspectives.The application of clinical genetics · 2019
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 2 countries.

Kirsten C MorleyUniversity of Sydney, Faculty of Medicine and Health, Central Clinical School, NHMRC Centre of Research Excellence in Mental Health and Substance Use, Sydney, NSW, Australia. kirsten.morley@sydney.edu.au.ORCID http://orcid.org/0000-0002-0868-9928
Henry R KranzlerCenter for Studies of Addiction, Perelman School of Medicine, University of Pennsylvania and Mental Illness Research, Education, and Clinical Center, Crescenz VAMC, Philadelphia, PA, USA.
Natasha LuquinDepartment of Medical Genomics, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
Andrew BaillieFaculty of Medicine and Health, Health Sciences NHMRC Centre of Research Excellence in Mental Health and Substance Use, University of Sydney, Sydney, NSW, Australia.
Marian ShanahanNational Drug and Alcohol Research Centre, UNSW, Sydney, NSW, Australia.
Ronald TrentDepartment of Medical Genomics, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
Maree TeessonNHMRC Centre of Research Excellence in Mental Health and Substance Use, National Drug and Alcohol Research Centre, UNSW, Sydney, NSW, Australia.
Paul S HaberUniversity of Sydney, Faculty of Medicine and Health, Central Clinical School, NHMRC Centre of Research Excellence in Mental Health and Substance Use, Sydney, NSW, Australia.
The University of Sydney · AURoyal Prince Alfred Hospital · AUUNSW Sydney · AUUniversity of Pennsylvania · US

Funding

National Health and Medical Research Council APP1104288
6 · The paper itself

Abstract

backgroundCurrent treatments for alcohol use disorders have limited efficacy and there is a high degree of variability in treatment response. In a randomised, placebo-controlled clinical trial, there was a large effect size for topiramate in people homozygous for the GRIK1 rs2832407*C allele. The primary aim of the TOP study is to examine prospectively the therapeutic and cost-effectiveness of topiramate versus an active control (naltrexone) in improving treatment outcomes for alcohol dependence. Participants will be stratified on rs2832407 to compare C-allele homozygotes with A-allele carriers to examine the moderating effect of rs2832407 on drinking outcomes. An exploratory aim is to examine the moderating effects of rs1799971, a polymorphism in OPRM1, on the response to naltrexone by comparing Asn40 homozygotes with Asp40 carriers. METHODS/

designThis double-blind trial will randomise 180 alcohol-dependent participants to a 12-week regime of either topiramate (titrating the dose up to 200 mg/day) or naltrexone (50 mg/day). Participants will be stratified on the two polymorphisms before randomisation. All participants will receive medical management. The primary drinking outcome will be the number of heavy drinking days per week and secondary drinking outcomes will include the time to relapse, the time to lapse and the percentage of abstinent days. Other secondary outcomes will include body mass index, tobacco use, anxiety symptoms and depressive symptoms. DISCUSSION: If successful, the TOP study will improve management strategies for alcohol dependence by providing support for the use of genetic biomarkers to inform medication selection.

trial registrationClinicalTrials.gov, NCT03479086 . Registered on 27 March 2018.

Indexed as

AdolescentAdultAgedAlcohol AbstinenceAlcohol DrinkingAlcoholismClinical ProtocolsDouble-Blind MethodExcitatory Amino Acid AntagonistsFemaleGene FrequencyHomozygoteHumansKainic Acid ReceptorsMaleMiddle AgedExcitatory Amino Acid AntagonistsKainic Acid ReceptorsNaltrexoneNarcotic AntagonistsOPRM1 protein, humanReceptors, Opioid, muTopiramateAlcohol dependenceAlcohol use disorderGRIK1NaltrexoneOPRM1PharmacogeneticsTopiramate

Identifiers

PMID30115121
PMCPMC6097336
OpenAlexW2887753982

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.