Trials (Jun 2024)

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

DOI
https://doi.org/10.1186/s13063-024-08238-y
Journal volume & issue
Vol. 25, no. 1
pp. 1 – 12

Abstract

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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.

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