{
  "abstract": "Introduction Progressive supranuclear palsy (PSP) is a devastating neurodegenerative disease characterised by cognitive, behavioural and motor problems. Motor symptoms are highly disabling, while cognitive and behavioural changes have a major impact on carer burden, quality of life and prognosis. Apathy and impulsivity are very common, often coexistent in PSP, and negatively predict survival. In preclinical models and other diseases, apathy and impulsivity are associated with noradrenergic deficits, which can be severe in PSP.Methods and analysis Noradrenaline for Progressive Supranuclear Palsy Syndromes trial is a randomised, double-blind, placebo-controlled, crossover design, Phase IIb clinical trial to evaluate the efficacy and safety of oral atomoxetine for the treatment of cognitive and behavioural changes in PSP. Participants receive atomoxetine 40 mg (10 mg/mL oral solution) once daily or a matched placebo solution, in random order, each for 8 weeks. An ‘informant’, who knows the patient with PSP well, is co-recruited to complete some of the trial outcome measures. Participants remain in the trial for 22 weeks after randomisation. The primary objectives are to assess (1) safety and tolerability and (2) efficacy versus placebo on challenging behaviours as reported in a subscale of the Cambridge Behavioural Inventory. Secondary and exploratory measures relate to cognition, the PSP Rating Scale, mood and potential baseline predictors of individual response to atomoxetine computed from imaging, genetic and cognitive measures at baseline.Ethics and dissemination The trial was approved by the South Central-Oxford B Research Ethics Committee (REC) and the Medicines and Healthcare products Regulatory Agency (REC reference: 20/SC/0416). Dissemination will include publication in peer-reviewed journals, presentations at academic and public conferences and engagement with patients, the public, policymakers and practitioners.Trial registration number ISRCTN99462035; DOI: https://doi.org/10.1186/ISRCTN99462035; EudraCT (European Union Drug Regulating Authorities Clinical Trials Database)/CTIS (Clinical Trial Information System) number: 2019-004472-19; IRAS (Integrated Research Application System) number: 272063; Secondary identifying numbers: CPMS (Central Portfolio Management System) 44441.",
  "authors": [
    {
      "affiliations": [
        "Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK",
        "Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK"
      ],
      "name": "Robert Durcan"
    },
    {
      "affiliations": [
        "Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"
      ],
      "name": "Hugo Paula"
    },
    {
      "affiliations": [
        "Wessex Neurological Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK"
      ],
      "name": "Boyd C P Ghosh"
    },
    {
      "affiliations": [
        "Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"
      ],
      "name": "Duncan Street"
    },
    {
      "affiliations": [
        "Norwich Clinical Trials Unit, University of East Anglia, Norwich, UK"
      ],
      "name": "Juliet High"
    },
    {
      "affiliations": [
        "Norwich Clinical Trials Unit, University of East Anglia, Norwich, UK"
      ],
      "name": "Colin McAlister"
    },
    {
      "affiliations": [
        "Norwich Clinical Trials Unit, University of East Anglia, Norwich, UK"
      ],
      "name": "Lee Shepstone"
    },
    {
      "affiliations": [
        "Norwich Clinical Trials Unit, University of East Anglia, Norwich, UK"
      ],
      "name": "Charlotte Russell"
    },
    {
      "affiliations": [
        "Norwich Clinical Trials Unit, University of East Anglia, Norwich, UK"
      ],
      "name": "Kelly Grant"
    },
    {
      "affiliations": [
        "Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK"
      ],
      "name": "Natalia Igosheva"
    },
    {
      "affiliations": [
        "Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"
      ],
      "name": "Christopher T Rodgers"
    },
    {
      "affiliations": [
        "Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"
      ],
      "name": "Simon P Jones"
    },
    {
      "affiliations": [
        "Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"
      ],
      "name": "Rong Ye"
    },
    {
      "affiliations": [
        "Manchester Centre for Clinical Neurosciences, Northern Care Alliance NHS Foundation Trust, Salford, UK"
      ],
      "name": "Christopher Kobylecki"
    },
    {
      "affiliations": [
        "Royal Gwent Hospital, Newport, UK"
      ],
      "name": "Alistair Church"
    },
    {
      "affiliations": [
        "Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK"
      ],
      "name": "Chrystalina Antoniades"
    },
    {
      "affiliations": [
        "Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, UK"
      ],
      "name": "Vicky Marshall"
    },
    {
      "affiliations": [
        "Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK"
      ],
      "name": "Luca Passamonti"
    },
    {
      "affiliations": [
        "Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK",
        "Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK",
        "MRC Cognition and Brain Sciences Unit, Cambridge, UK"
      ],
      "name": "James B Rowe"
    }
  ],
  "title": "Noradrenaline for progressive supranuclear palsy syndromes (NORAPS): a randomised, double-blind, placebo-controlled, crossover Phase IIb clinical trial evaluating the efficacy and safety of oral atomoxetine for treating cognitive and behavioural changes in people with progressive supranuclear palsy syndromes in the UK",
  "uid": "c82700f4-e321-522b-af1a-bf45b3a41634"
}