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.

Humans Mirtazapine / therapeutic use Double-Blind Method Amphetamine-Related Disorders / drug therapy Methamphetamine / adverse effects Adult Middle Aged Adolescent Clinical Trials, Phase III as Topic Male Young Adult Randomized Controlled Trials as Topic Aged Female Treatment Outcome Multicenter Studies as Topic Australia Time Factors Medication Adherence Antidepressive Agents, Tricyclic / therapeutic use
Addiction Clinical trial Depression Methamphetamine Mirtazapine Pharmacotherapy Psychiatry Sleep Substance use disorders Treatment

Journal

Trials
ISSN: 1745-6215
Titre abrégé: Trials
Pays: England
ID NLM: 101263253

Informations de publication

Date de publication:
22 Jun 2024
Historique:
received: 01 03 2024
accepted: 10 06 2024
medline: 22 6 2024
pubmed: 22 6 2024
entrez: 21 6 2024
Statut: epublish

Résumé

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. 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. 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. Australian and New Zealand Clinical Trials Registry ACTRN12622000235707. Registered on February 9, 2022.

Sections du résumé

BACKGROUND 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 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 CONCLUSIONS
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 BACKGROUND
Australian and New Zealand Clinical Trials Registry ACTRN12622000235707. Registered on February 9, 2022.

Identifiants

DOI: 10.1186/s13063-024-08238-y PMID: 38907288
pubmed: 38907288
doi: 10.1186/s13063-024-08238-y
pii: 10.1186/s13063-024-08238-y
doi:

Substances chimiques

Mirtazapine A051Q2099Q
Methamphetamine 44RAL3456C
Antidepressive Agents, Tricyclic 0

Types de publication

Clinical Trial Protocol Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

408

Subventions

Organisme : Medical Research Future Fund (AU)
ID : 2007155

Informations de copyright

© 2024. The Author(s).

Références

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Auteurs

Rebecca McKetin (R)

National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia. r.mcketin@unsw.edu.au.
ORCID: 0000-0003-2833-4830

Tayla J Degan (TJ)

National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia.

Lucy Saunders (L)

National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia.

Long Nguyen (L)

Burnet Institute, Melbourne, Australia.

Gregory Dore (G)

Kirby Institute, University of New South Wales, Sydney, Australia.

Steven Shoptaw (S)

Department of Family Medicine, David Geffen School of Medicine, Los Angeles, USA.

Michael Farrell (M)

National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia.

Louisa Degenhardt (L)

National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia.

Peter J Kelly (PJ)

School of Psychology, Faculty of Arts, Social Sciences and Humanities, University of Wollongong, Wollongong, Australia.

Alyna Turner (A)

IMPACT, School of Medicine, Deakin University, Geelong, Australia.

Philip J Clare (PJ)

Prevention Research Collaboration, The University of Sydney, Sydney, Australia.

Olivia M Dean (OM)

IMPACT, School of Medicine, Deakin University, Geelong, Australia.

Shalini Arunogiri (S)

Alfred Psychiatry Research Centre (MAPrc), Central Clinical School, Monash University, Melbourne, Australia.

Samantha Colledge-Frisby (S)

Burnet Institute, Melbourne, Australia.
National Drug Research Institute, Curtin University, Perth, Australia.

Juanita Koeijers (J)

National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia.

David Goodman-Meza (D)

Center for HIV Identification, Prevention, and Treatment Services, Los Angeles, USA.

Barbara Sinclair (B)

Illawarra Drug and Alcohol Service, Illawarra Shoalhaven Local Health District, NSW Health, Wollongong, Australia.

David Reid (D)

Illawarra Drug and Alcohol Service, Illawarra Shoalhaven Local Health District, NSW Health, Wollongong, Australia.

Harry Hill (H)

Drug and Alcohol Services, Barwon Health, Geelong, Australia.

Jeremy Hayllar (J)

Biala City Community Health Centre, Metro North Health, Brisbane, Australia.

Michael Christmass (M)

Next Step Community Alcohol and Drug Service East Perth, East Perth, Australia.

Frank Cordaro (F)

Illawarra Drug and Alcohol Service, Illawarra Shoalhaven Local Health District, NSW Health, Wollongong, Australia.

Robert Lundin (R)

Drug and Alcohol Services, Barwon Health, Geelong, Australia.

Willy Liaw (W)

Drug and Alcohol Services of South Australia, Adelaide, Australia.

Danica Liu (D)

Drug and Alcohol Services of South Australia, Adelaide, Australia.

Ellie Holyoak (E)

Alcohol, Tobacco & Other Drug Services, Townsville, Australia.

Brian Tid-Fung Wu (BT)

Alcohol, Tobacco & Other Drug Services, Townsville, Australia.

Joel Keygan (J)

National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia.

Ava Kontogiannis (A)

School of Psychology, Faculty of Arts, Social Sciences and Humanities, University of Wollongong, Wollongong, Australia.

Lily Palmer (L)

National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia.

Caity Morrison (C)

IMPACT, School of Medicine, Deakin University, Geelong, Australia.

Anna Wrobel (A)

IMPACT, School of Medicine, Deakin University, Geelong, Australia.

Bec Hyland (B)

National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia.

Marianne Byrne (M)

Kirby Institute, University of New South Wales, Sydney, Australia.

Samantha Russell (S)

IMPACT, School of Medicine, Deakin University, Geelong, Australia.
Grampians Health, Ballarat, Australia.

Emma Zahra (E)

National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia.

Michael Berk (M)

IMPACT, School of Medicine, Deakin University, Geelong, Australia.
Drug and Alcohol Services, Barwon Health, Geelong, Australia.
Florey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia.

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