A phase 3 randomised double-blind placebo-controlled trial of mirtazapine as a pharmacotherapy for methamphetamine use disorder: a study protocol for the Tina Trial
Rebecca McKetin,
Tayla J. Degan,
Lucy Saunders,
Long Nguyen,
Gregory Dore,
Steven Shoptaw,
Michael Farrell,
Louisa Degenhardt,
Peter J. Kelly,
Alyna Turner,
Philip J. Clare,
Olivia M. Dean,
Shalini Arunogiri,
Samantha Colledge-Frisby,
Juanita Koeijers,
David Goodman-Meza,
Barbara Sinclair,
David Reid,
Harry Hill,
Jeremy Hayllar,
Michael Christmass,
Frank Cordaro,
Robert Lundin,
Willy Liaw,
Danica Liu,
Ellie Holyoak,
Brian Tid-Fung Wu,
Joel Keygan,
Ava Kontogiannis,
Lily Palmer,
Caity Morrison,
Anna Wrobel,
Bec Hyland,
Marianne Byrne,
Samantha Russell,
Emma Zahra,
Michael Berk
Affiliations
Rebecca McKetin
National Drug and Alcohol Research Centre, University of New South Wales
Tayla J. Degan
National Drug and Alcohol Research Centre, University of New South Wales
Lucy Saunders
National Drug and Alcohol Research Centre, University of New South Wales
Long Nguyen
Burnet Institute
Gregory Dore
Kirby Institute, University of New South Wales
Steven Shoptaw
Department of Family Medicine, David Geffen School of Medicine
Michael Farrell
National Drug and Alcohol Research Centre, University of New South Wales
Louisa Degenhardt
National Drug and Alcohol Research Centre, University of New South Wales
Peter J. Kelly
School of Psychology, Faculty of Arts, Social Sciences and Humanities, University of Wollongong
Alyna Turner
IMPACT, School of Medicine, Deakin University
Philip J. Clare
Prevention Research Collaboration, The University of Sydney
Olivia M. Dean
IMPACT, School of Medicine, Deakin University
Shalini Arunogiri
Alfred Psychiatry Research Centre (MAPrc), Central Clinical School, Monash University
Samantha Colledge-Frisby
Burnet Institute
Juanita Koeijers
National Drug and Alcohol Research Centre, University of New South Wales
David Goodman-Meza
Center for HIV Identification, Prevention, and Treatment Services
Barbara Sinclair
Illawarra Drug and Alcohol Service, Illawarra Shoalhaven Local Health District, NSW Health
David Reid
Illawarra Drug and Alcohol Service, Illawarra Shoalhaven Local Health District, NSW Health
Harry Hill
Drug and Alcohol Services, Barwon Health
Jeremy Hayllar
Biala City Community Health Centre, Metro North Health
Michael Christmass
Next Step Community Alcohol and Drug Service East Perth
Frank Cordaro
Illawarra Drug and Alcohol Service, Illawarra Shoalhaven Local Health District, NSW Health
Robert Lundin
Drug and Alcohol Services, Barwon Health
Willy Liaw
Drug and Alcohol Services of South Australia
Danica Liu
Drug and Alcohol Services of South Australia
Ellie Holyoak
Alcohol, Tobacco & Other Drug Services
Brian Tid-Fung Wu
Alcohol, Tobacco & Other Drug Services
Joel Keygan
National Drug and Alcohol Research Centre, University of New South Wales
Ava Kontogiannis
School of Psychology, Faculty of Arts, Social Sciences and Humanities, University of Wollongong
Lily Palmer
National Drug and Alcohol Research Centre, University of New South Wales
Caity Morrison
IMPACT, School of Medicine, Deakin University
Anna Wrobel
IMPACT, School of Medicine, Deakin University
Bec Hyland
National Drug and Alcohol Research Centre, University of New South Wales
Marianne Byrne
Kirby Institute, University of New South Wales
Samantha Russell
IMPACT, School of Medicine, Deakin University
Emma Zahra
National Drug and Alcohol Research Centre, University of New South Wales
Abstract Background There are no approved pharmacotherapies for methamphetamine use disorder. Two preliminary phase 2 randomised controlled trials have found mirtazapine, a tetracyclic antidepressant, to be effective in reducing methamphetamine use. The proposed Tina Trial is the first phase 3 placebo-controlled randomised trial to examine the effectiveness and safety of mirtazapine as an outpatient pharmacotherapy for methamphetamine use disorder. Methods This is a multi-site phase 3 randomised, double-blind, placebo-controlled parallel trial. Participants are randomly allocated (1:1) to receive either mirtazapine (30 mg/day for 12 weeks) or matched placebo, delivered as a take-home medication. The target population is 340 people aged 18–65 years who have moderate to severe methamphetamine use disorder. The trial is being conducted through outpatient alcohol and other drug treatment clinics in Australia. The primary outcome is measured as self-reported days of methamphetamine use in the past 4 weeks at week 12. Secondary outcomes are methamphetamine-negative oral fluid samples, depressive symptoms, sleep quality, HIV risk behaviour and quality of life. Other outcomes include safety (adverse events), tolerability, and health service use. Medication adherence is being monitored using MEMS® Smart Caps fitted to medication bottles. Discussion This trial will provide information on the safety and effectiveness of mirtazapine as a pharmacotherapy for methamphetamine use disorder when delivered as an outpatient medication in routine clinical practice. If found to be safe and effective, this trial will support an application for methamphetamine use disorder to be included as a therapeutic indication for the prescription of mirtazapine. Trial registration Australian and New Zealand Clinical Trials Registry ACTRN12622000235707. Registered on February 9, 2022.
