title: Study protocol: a dose-escalating, phase-2 study of oral lisdexamfetamine in adults with methamphetamine dependence.
abstract: BACKGROUND
  The treatment of methamphetamine dependence is a continuing global health problem. Agonist type pharmacotherapies have been used successfully to treat opioid and nicotine dependence and are being studied for the treatment of methamphetamine dependence. One potential candidate is lisdexamfetamine, a pro-drug for dexamphetamine, which has a longer lasting therapeutic action with a lowered abuse potential. The purpose of this study is to determine the safety of lisdexamfetamine in this population at doses higher than those currently approved for attention deficit hyperactivity disorder or binge eating disorder.
  
  
  METHODS
  This is a phase 2 dose escalation study of lisdexamfetamine for the treatment of methamphetamine dependence. Twenty individuals seeking treatment for methamphetamine dependence will be recruited at two Australian drug and alcohol services. All participants will undergo a single-blinded ascending-descending dose regime of 100 to 250 mg lisdexamfetamine, dispensed daily on site, over an 8-week period. Participants will be offered counselling as standard care. For the primary objectives the outcome variables will be adverse events monitoring, drug tolerability and regimen completion. Secondary outcomes will be changes in methamphetamine use, craving, withdrawal, severity of dependence, risk behaviour and other substance use. Medication acceptability, potential for non-prescription use, adherence and changes in neurocognition will also be measured.
  
  
  CONCLUSIONS
  Determining the safety of lisdexamfetamine will enable further research to develop pharmacotherapies for the treatment of methamphetamine dependence.
  
  
  BACKGROUND
  Australian and New Zealand Clinical Trials Registry ACTRN12615000391572 Registered 28thApril 2015.
authors.affiliation: Alcohol and Drug Service, O'Brien Centre, St Vincent's Hospital, Sydney, Darlinghurst, 2010, NSW, Australia.|St Vincent's Hospital Clinical School, Faculty of Medicine, UNSW, Sydney, Australia.
authors.forename: Nadine
authors.initials: N
authors.lastname: Ezard
authors.affiliation: Drug and Alcohol Clinical Services, Hunter New England Local Health District, Newcastle Community Health Centre, Newcastle, 2302, NSW, Australia.
authors.forename: Adrian
authors.initials: A
authors.lastname: Dunlop
authors.affiliation: Alcohol and Drug Service, O'Brien Centre, St Vincent's Hospital, Sydney, Darlinghurst, 2010, NSW, Australia. brendan.clifford@svha.org.au.
authors.forename: Brendan
authors.identifier: http://orcid.org/0000-0002-9178-9013
authors.initials: B
authors.lastname: Clifford
authors.affiliation: School of Medicine, University of Tasmania, Private Bag 30, Hobart, 7001, TAS, Australia.
authors.forename: Raimondo
authors.initials: R
authors.lastname: Bruno
authors.affiliation: Centre for Applied Medical Research, St Vincent's Hospital, 390 Victoria Street, Darlinghurst, 2010, NSW, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Carr
authors.affiliation: Alcohol and Drug Service, O'Brien Centre, St Vincent's Hospital, Sydney, Darlinghurst, 2010, NSW, Australia.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Bissaker
authors.affiliation: South East Sydney Local Health District, The Langton Centre, 591 South Dowling St, Surry Hills, 2010, NSW, Australia.|Discipline of Addiction Medicine and Lambert initiative in Cannabinoid Therapeutics, University of Sydney, Sydney, 2006, NSW, Australia.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Lintzeris
mesh_terms: D000328:Adult; D019969:Amphetamine-Related Disorders / Q000188:drug therapy*; D001315:Australia; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000627:therapeutic use*; D003376:Counseling / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000069478:Lisdexamfetamine Dimesylate / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008694:Methamphetamine; D016037:Single-Blind Method; D016896:Treatment Outcome
chemical_list: D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D000069478:Lisdexamfetamine Dimesylate
keywords: Dose-finding; Lisdexamfetamine; Methamphetamine; Pharmacotherapy; Stimulant use disorder; Study protocol