Cargando…
A study protocol for the N-ICE trial: A randomised double-blind placebo-controlled study of the safety and efficacy of N-acetyl-cysteine (NAC) as a pharmacotherapy for methamphetamine (“ice”) dependence
BACKGROUND: There are currently no approved pharmacotherapies for managing methamphetamine dependence. N-acetylcysteine (NAC) has been found to reduce the craving for methamphetamine and other drugs, but its effect on methamphetamine use and other clinically related endpoints are uncertain. The N-IC...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549263/ https://www.ncbi.nlm.nih.gov/pubmed/31164169 http://dx.doi.org/10.1186/s13063-019-3450-0 |
_version_ | 1783423968703676416 |
---|---|
author | McKetin, Rebecca Dean, Olivia M. Turner, Alyna Kelly, Peter J. Quinn, Brendan Lubman, Dan I. Dietze, Paul Carter, Gregory Higgs, Peter Baker, Amanda L. Sinclair, Barbara Reid, David Manning, Victoria te Pas, Nina Liang, Wenbin Thomas, Tamsin Bathish, Ramez Kent, Margaret Raftery, Dayle Arunogiri, Shalini Cordaro, Frank Hill, Harry Berk, Michael |
author_facet | McKetin, Rebecca Dean, Olivia M. Turner, Alyna Kelly, Peter J. Quinn, Brendan Lubman, Dan I. Dietze, Paul Carter, Gregory Higgs, Peter Baker, Amanda L. Sinclair, Barbara Reid, David Manning, Victoria te Pas, Nina Liang, Wenbin Thomas, Tamsin Bathish, Ramez Kent, Margaret Raftery, Dayle Arunogiri, Shalini Cordaro, Frank Hill, Harry Berk, Michael |
author_sort | McKetin, Rebecca |
collection | PubMed |
description | BACKGROUND: There are currently no approved pharmacotherapies for managing methamphetamine dependence. N-acetylcysteine (NAC) has been found to reduce the craving for methamphetamine and other drugs, but its effect on methamphetamine use and other clinically related endpoints are uncertain. The N-ICE trial is evaluating the safety and efficacy of NAC as a take-home pharmacotherapy for methamphetamine dependence. METHODS/DESIGN: This is a two-arm parallel double-blind placebo-controlled three-site randomised trial (ratio 1:1) using permuted block randomisation, with variable block sizes. It is stratified by site, sex and whether the methamphetamine is injected or not. Participants (N = 180; 60 per site) need to be dependent on methamphetamine, interested in reducing their methamphetamine use and not currently receiving treatment for substance use disorders. The trial is being conducted in outpatient settings in Melbourne, Geelong and Wollongong, Australia. Participants will receive either 2400 mg oral NAC or a matched placebo, delivered as a take-home medication for 12 weeks. Two 600 mg capsules are self-administered in the morning and two more in the evening. Adherence is being monitored using eCAP™ medication bottle lids, which record the date and time of each occasion the bottle is opened. The primary outcome is methamphetamine use during the 12-week trial medication period, measured as (a) days of use, assessed using the timeline followback, and (b) methamphetamine-positive saliva tests, taken weekly. Secondary measures include weekly assessment of methamphetamine craving, severity of methamphetamine dependence, methamphetamine withdrawal symptoms and psychiatric symptoms (depression, suicidality, psychotic symptoms and hostility). Adverse events are monitored at each weekly assessment. Tolerability is assessed using the Treatment Satisfaction Questionnaire for Medication. DISCUSSION: The N-ICE trial is the first clinical trial to assess whether NAC can reduce methamphetamine use. This trial will improve our understanding of the potential utility of NAC in managing methamphetamine dependence and clinically related outcomes. If found to be effective, take-home NAC could be a potentially scalable and affordable pharmacotherapy option for treating methamphetamine dependence. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, ACTRN12618000366257. Registered on 29 May 2018. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13063-019-3450-0) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6549263 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-65492632019-06-06 A study protocol for the N-ICE trial: A randomised double-blind placebo-controlled study of the safety and efficacy of N-acetyl-cysteine (NAC) as a pharmacotherapy for methamphetamine (“ice”) dependence McKetin, Rebecca Dean, Olivia M. Turner, Alyna Kelly, Peter J. Quinn, Brendan Lubman, Dan I. Dietze, Paul Carter, Gregory Higgs, Peter Baker, Amanda L. Sinclair, Barbara Reid, David Manning, Victoria te Pas, Nina Liang, Wenbin Thomas, Tamsin Bathish, Ramez Kent, Margaret Raftery, Dayle Arunogiri, Shalini Cordaro, Frank Hill, Harry Berk, Michael Trials Study Protocol BACKGROUND: There are currently no approved pharmacotherapies for managing methamphetamine dependence. N-acetylcysteine (NAC) has been found to reduce the craving for methamphetamine and other drugs, but its effect on methamphetamine use and other clinically related endpoints are uncertain. The N-ICE trial is evaluating the safety and efficacy of NAC as a take-home pharmacotherapy for methamphetamine dependence. METHODS/DESIGN: This is a two-arm parallel double-blind placebo-controlled three-site randomised trial (ratio 1:1) using permuted block randomisation, with variable block sizes. It is stratified by site, sex and whether the methamphetamine is injected or not. Participants (N = 180; 60 per site) need to be dependent on methamphetamine, interested in reducing their methamphetamine use and not currently receiving treatment for substance use disorders. The trial is being conducted in outpatient settings in Melbourne, Geelong and Wollongong, Australia. Participants will receive either 2400 mg oral NAC or a matched placebo, delivered as a take-home medication for 12 weeks. Two 600 mg capsules are self-administered in the morning and two more in the evening. Adherence is being monitored using eCAP™ medication bottle lids, which record the date and time of each occasion the bottle is opened. The primary outcome is methamphetamine use during the 12-week trial medication period, measured as (a) days of use, assessed using the timeline followback, and (b) methamphetamine-positive saliva tests, taken weekly. Secondary measures include weekly assessment of methamphetamine craving, severity of methamphetamine dependence, methamphetamine withdrawal symptoms and psychiatric symptoms (depression, suicidality, psychotic symptoms and hostility). Adverse events are monitored at each weekly assessment. Tolerability is assessed using the Treatment Satisfaction Questionnaire for Medication. DISCUSSION: The N-ICE trial is the first clinical trial to assess whether NAC can reduce methamphetamine use. This trial will improve our understanding of the potential utility of NAC in managing methamphetamine dependence and clinically related outcomes. If found to be effective, take-home NAC could be a potentially scalable and affordable pharmacotherapy option for treating methamphetamine dependence. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, ACTRN12618000366257. Registered on 29 May 2018. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13063-019-3450-0) contains supplementary material, which is available to authorized users. BioMed Central 2019-06-04 /pmc/articles/PMC6549263/ /pubmed/31164169 http://dx.doi.org/10.1186/s13063-019-3450-0 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Study Protocol McKetin, Rebecca Dean, Olivia M. Turner, Alyna Kelly, Peter J. Quinn, Brendan Lubman, Dan I. Dietze, Paul Carter, Gregory Higgs, Peter Baker, Amanda L. Sinclair, Barbara Reid, David Manning, Victoria te Pas, Nina Liang, Wenbin Thomas, Tamsin Bathish, Ramez Kent, Margaret Raftery, Dayle Arunogiri, Shalini Cordaro, Frank Hill, Harry Berk, Michael A study protocol for the N-ICE trial: A randomised double-blind placebo-controlled study of the safety and efficacy of N-acetyl-cysteine (NAC) as a pharmacotherapy for methamphetamine (“ice”) dependence |
title | A study protocol for the N-ICE trial: A randomised double-blind placebo-controlled study of the safety and efficacy of N-acetyl-cysteine (NAC) as a pharmacotherapy for methamphetamine (“ice”) dependence |
title_full | A study protocol for the N-ICE trial: A randomised double-blind placebo-controlled study of the safety and efficacy of N-acetyl-cysteine (NAC) as a pharmacotherapy for methamphetamine (“ice”) dependence |
title_fullStr | A study protocol for the N-ICE trial: A randomised double-blind placebo-controlled study of the safety and efficacy of N-acetyl-cysteine (NAC) as a pharmacotherapy for methamphetamine (“ice”) dependence |
title_full_unstemmed | A study protocol for the N-ICE trial: A randomised double-blind placebo-controlled study of the safety and efficacy of N-acetyl-cysteine (NAC) as a pharmacotherapy for methamphetamine (“ice”) dependence |
title_short | A study protocol for the N-ICE trial: A randomised double-blind placebo-controlled study of the safety and efficacy of N-acetyl-cysteine (NAC) as a pharmacotherapy for methamphetamine (“ice”) dependence |
title_sort | study protocol for the n-ice trial: a randomised double-blind placebo-controlled study of the safety and efficacy of n-acetyl-cysteine (nac) as a pharmacotherapy for methamphetamine (“ice”) dependence |
topic | Study Protocol |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549263/ https://www.ncbi.nlm.nih.gov/pubmed/31164169 http://dx.doi.org/10.1186/s13063-019-3450-0 |
work_keys_str_mv | AT mcketinrebecca astudyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT deanoliviam astudyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT turneralyna astudyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT kellypeterj astudyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT quinnbrendan astudyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT lubmandani astudyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT dietzepaul astudyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT cartergregory astudyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT higgspeter astudyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT bakeramandal astudyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT sinclairbarbara astudyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT reiddavid astudyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT manningvictoria astudyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT tepasnina astudyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT liangwenbin astudyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT thomastamsin astudyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT bathishramez astudyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT kentmargaret astudyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT rafterydayle astudyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT arunogirishalini astudyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT cordarofrank astudyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT hillharry astudyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT berkmichael astudyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT mcketinrebecca studyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT deanoliviam studyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT turneralyna studyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT kellypeterj studyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT quinnbrendan studyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT lubmandani studyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT dietzepaul studyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT cartergregory studyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT higgspeter studyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT bakeramandal studyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT sinclairbarbara studyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT reiddavid studyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT manningvictoria studyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT tepasnina studyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT liangwenbin studyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT thomastamsin studyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT bathishramez studyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT kentmargaret studyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT rafterydayle studyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT arunogirishalini studyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT cordarofrank studyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT hillharry studyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence AT berkmichael studyprotocolforthenicetrialarandomiseddoubleblindplacebocontrolledstudyofthesafetyandefficacyofnacetylcysteinenacasapharmacotherapyformethamphetamineicedependence |