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

Rebecca McKetin, Olivia M. Dean, Alyna Turner, Peter J. Kelly, Brendan Quinn, Dan I. Lubman, Paul Dietze, Gregory Carter, Peter Higgs, Amanda L. Baker, Barbara Sinclair, David Reid, Victoria Manning, Nina Te Pas, Wenbin Liang, Tamsin Thomas, Ramez Bathish, Margaret Kent, Dayle Raftery, Shalini Arunogiri & 3 others Frank Cordaro, Harry Hill, Michael Berk

Research output: Contribution to journalArticleOtherpeer-review

Abstract

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.

Original languageEnglish
Article number325
JournalTrials
Volume20
Issue number1
DOIs
Publication statusPublished - 4 Jun 2019

Keywords

  • aggression
  • clinical trial
  • craving
  • depression
  • methamphetamine
  • N-acetylcysteine
  • psychosis
  • substance use disorders
  • suicide
  • withdrawal

Cite this

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. In: Trials. 2019 ; Vol. 20, No. 1.
@article{9458407a3bba4a089694249048f30144,
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",
abstract = "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.",
keywords = "aggression, clinical trial, craving, depression, methamphetamine, N-acetylcysteine, psychosis, substance use disorders, suicide, withdrawal",
author = "Rebecca McKetin and Dean, {Olivia M.} and Alyna Turner and Kelly, {Peter J.} and Brendan Quinn and Lubman, {Dan I.} and Paul Dietze and Gregory Carter and Peter Higgs and Baker, {Amanda L.} and Barbara Sinclair and David Reid and Victoria Manning and {Te Pas}, Nina and Wenbin Liang and Tamsin Thomas and Ramez Bathish and Margaret Kent and Dayle Raftery and Shalini Arunogiri and Frank Cordaro and Harry Hill and Michael Berk",
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language = "English",
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McKetin, R, Dean, OM, Turner, A, Kelly, PJ, Quinn, B, Lubman, DI, Dietze, P, Carter, G, Higgs, P, Baker, AL, Sinclair, B, Reid, D, Manning, V, Te Pas, N, Liang, W, Thomas, T, Bathish, R, Kent, M, Raftery, D, Arunogiri, S, Cordaro, F, Hill, H & Berk, M 2019, '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', Trials, vol. 20, no. 1, 325. https://doi.org/10.1186/s13063-019-3450-0

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.

In: Trials, Vol. 20, No. 1, 325, 04.06.2019.

Research output: Contribution to journalArticleOtherpeer-review

TY - JOUR

T1 - A study protocol for the N-ICE trial

T2 - A randomised double-blind placebo-controlled study of the safety and efficacy of N-acetyl-cysteine (NAC) as a pharmacotherapy for methamphetamine ("ice") dependence

AU - McKetin, Rebecca

AU - Dean, Olivia M.

AU - Turner, Alyna

AU - Kelly, Peter J.

AU - Quinn, Brendan

AU - Lubman, Dan I.

AU - Dietze, Paul

AU - Carter, Gregory

AU - Higgs, Peter

AU - Baker, Amanda L.

AU - Sinclair, Barbara

AU - Reid, David

AU - Manning, Victoria

AU - Te Pas, Nina

AU - Liang, Wenbin

AU - Thomas, Tamsin

AU - Bathish, Ramez

AU - Kent, Margaret

AU - Raftery, Dayle

AU - Arunogiri, Shalini

AU - Cordaro, Frank

AU - Hill, Harry

AU - Berk, Michael

PY - 2019/6/4

Y1 - 2019/6/4

N2 - 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.

AB - 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.

KW - aggression

KW - clinical trial

KW - craving

KW - depression

KW - methamphetamine

KW - N-acetylcysteine

KW - psychosis

KW - substance use disorders

KW - suicide

KW - withdrawal

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