title: The Imperial College Cambridge Manchester (ICCAM) platform study: An experimental medicine platform for evaluating new drugs for relapse prevention in addiction. Part A: Study description.
abstract: Drug and alcohol dependence are global problems with substantial societal costs. There are few treatments for relapse prevention and therefore a pressing need for further study of brain mechanisms underpinning relapse circuitry. The Imperial College Cambridge Manchester (ICCAM) platform study is an experimental medicine approach to this problem: using functional magnetic resonance imaging (fMRI) techniques and selective pharmacological tools, it aims to explore the neuropharmacology of putative relapse pathways in cocaine, alcohol, opiate dependent, and healthy individuals to inform future drug development. Addiction studies typically involve small samples because of recruitment difficulties and attrition. We established the platform in three centres to assess the feasibility of a multisite approach to address these issues. Pharmacological modulation of reward, impulsivity and emotional reactivity were investigated in a monetary incentive delay task, an inhibitory control task, and an evocative images task, using selective antagonists for µ-opioid, dopamine D3 receptor (DRD3) and neurokinin 1 (NK1) receptors (naltrexone, GSK598809, vofopitant/aprepitant), in a placebo-controlled, randomised, crossover design. In two years, 609 scans were performed, with 155 individuals scanned at baseline. Attrition was low and the majority of individuals were sufficiently motivated to complete all five sessions (n=87). We describe herein the study design, main aims, recruitment numbers, sample characteristics, and explain the test hypotheses and anticipated study outputs.
authors.affiliation: Centre for Neuropsychopharmacology, Imperial College London, London, UK.
authors.forename: Louise M
authors.initials: LM
authors.lastname: Paterson
authors.affiliation: Centre for Neuropsychopharmacology, Imperial College London, London, UK.
authors.forename: Remy S A
authors.initials: RS
authors.lastname: Flechais
authors.affiliation: Neuroscience and Psychiatry Unit, University of Manchester, Manchester, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Murphy
authors.affiliation: Centre for Neuropsychopharmacology, Imperial College London, London, UK.
authors.forename: Laurence J
authors.initials: LJ
authors.lastname: Reed
authors.affiliation: Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
authors.forename: Sanja
authors.initials: S
authors.lastname: Abbott
authors.affiliation: Neuroscience and Psychiatry Unit, University of Manchester, Manchester, UK.
authors.forename: Venkataramana
authors.initials: V
authors.lastname: Boyapati
authors.affiliation: Neuroscience and Psychiatry Unit, University of Manchester, Manchester, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Elliott
authors.affiliation: Centre for Neuropsychopharmacology, Imperial College London, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Erritzoe
authors.affiliation: Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: Karen D
authors.initials: KD
authors.lastname: Ersche
authors.affiliation: Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK.
authors.forename: Yetunde
authors.initials: Y
authors.lastname: Faluyi
authors.affiliation: Centre for Neuropsychopharmacology, Imperial College London, London, UK.
authors.forename: Luca
authors.initials: L
authors.lastname: Faravelli
authors.affiliation: Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK.
authors.forename: Emilio
authors.initials: E
authors.lastname: Fernandez-Egea
authors.affiliation: Centre for Neuropsychopharmacology, Imperial College London, London, UK.
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Kalk
authors.affiliation: Neuroscience and Psychiatry Unit, University of Manchester, Manchester, UK.
authors.forename: Shankar S
authors.initials: SS
authors.lastname: Kuchibatla
authors.affiliation: Centre for Neuropsychopharmacology, Imperial College London, London, UK.
authors.forename: John
authors.initials: J
authors.lastname: McGonigle
authors.affiliation: Neuroscience and Psychiatry Unit, University of Manchester, Manchester, UK 5 Boroughs Partnership NHS Foundation Trust, Warrington, UK.
authors.forename: Antonio
authors.initials: A
authors.lastname: Metastasio
authors.affiliation: Centre for Neuropsychopharmacology, Imperial College London, London, UK.
authors.forename: Inge
authors.initials: I
authors.lastname: Mick
authors.affiliation: Centre for Neuropsychopharmacology, Imperial College London, London, UK Clinical Research Unit, GlaxoSmithKline, Cambridge, UK.
authors.forename: Liam
authors.initials: L
authors.lastname: Nestor
authors.affiliation: Centre for Neuropsychopharmacology, Imperial College London, London, UK.
authors.forename: Csaba
authors.initials: C
authors.lastname: Orban
authors.affiliation: Centre for Neuropsychopharmacology, Imperial College London, London, UK Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: Filippo
authors.initials: F
authors.lastname: Passetti
authors.affiliation: Imanova Ltd, London, UK.
authors.forename: Eugenii A
authors.initials: EA
authors.lastname: Rabiner
authors.affiliation: Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK Department of Psychology, University of Cambridge, Cambridge, UK.
authors.forename: Dana G
authors.initials: DG
authors.lastname: Smith
authors.affiliation: Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK.
authors.forename: John
authors.initials: J
authors.lastname: Suckling
authors.affiliation: Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
authors.forename: Roger
authors.initials: R
authors.lastname: Tait
authors.affiliation: Neuroscience and Psychiatry Unit, University of Manchester, Manchester, UK.
authors.forename: Eleanor M
authors.initials: EM
authors.lastname: Taylor
authors.affiliation: Centre for Neuroinflammation and Neurodegeneration, Imperial College London, London, UK.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Waldman
authors.affiliation: Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK Department of Psychology, University of Cambridge, Cambridge, UK.
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Robbins
authors.affiliation: Neuroscience and Psychiatry Unit, University of Manchester, Manchester, UK.
authors.forename: J F William
authors.initials: JF
authors.lastname: Deakin
authors.affiliation: Centre for Neuropsychopharmacology, Imperial College London, London, UK d.nutt@imperial.ac.uk.
authors.forename: David J
authors.initials: DJ
authors.lastname: Nutt
authors.affiliation: Centre for Neuropsychopharmacology, Imperial College London, London, UK.
authors.forename: Anne R
authors.initials: AR
authors.lastname: Lingford-Hughes
mesh_terms: D000328:Adult; D016739:Behavior, Addictive / Q000378:metabolism / Q000517:prevention & control*; D035843:Biomedical Research / Q000379:methods*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003042:Cocaine / Q000009:adverse effects; D018592:Cross-Over Studies; D055808:Drug Discovery / Q000379:methods; D000431:Ethanol / Q000009:adverse effects; D005260:Female; D006801:Humans; D007175:Impulsive Behavior / Q000187:drug effects; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000378:metabolism; D064729:Neurokinin-1 Receptor Antagonists / Q000627:therapeutic use; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D012201:Reward; D055502:Secondary Prevention / Q000379:methods*; D019966:Substance-Related Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D064729:Neurokinin-1 Receptor Antagonists; D004364:Pharmaceutical Preparations; D050637:Receptors, Dopamine D3; D018040:Receptors, Neurokinin-1; D000431:Ethanol; D009271:Naltrexone; D003042:Cocaine
keywords: Addiction; dopamine D3 receptor; functional magnetic resonance imaging; neurokinin 1 receptor; µ-opioid receptor