Evidence map›Paper›PMID 40730397›Full record

ArticleBMJ open2025

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.

Robert Durcan, Hugo Paula, Boyd C P Ghosh, Duncan Street, Juliet High, Colin McAlister, Lee Shepstone, Charlotte Russell, Kelly Grant, Natalia Igosheva and 9 more

Abstract readClinical Trial Protocol
In one paragraph

Article in BMJ open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Robert DurcanDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, UK rd693@medschl.cam.ac.uk.ORCID http://orcid.org/0000-0001-9870-0117
Hugo PaulaDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0009-0001-5372-1480
Boyd C P GhoshWessex Neurological Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Duncan StreetDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Juliet HighNorwich Clinical Trials Unit, University of East Anglia, Norwich, UK.ORCID http://orcid.org/0000-0003-2555-2349
Colin McAlisterNorwich Clinical Trials Unit, University of East Anglia, Norwich, UK.
Lee ShepstoneNorwich Clinical Trials Unit, University of East Anglia, Norwich, UK.
Charlotte RussellNorwich Clinical Trials Unit, University of East Anglia, Norwich, UK.
Kelly GrantNorwich Clinical Trials Unit, University of East Anglia, Norwich, UK.
Natalia IgoshevaCambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Christopher T RodgersDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Simon P JonesDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Rong YeDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Christopher KobyleckiManchester Centre for Clinical Neurosciences, Northern Care Alliance NHS Foundation Trust, Salford, UK.
Alistair ChurchRoyal Gwent Hospital, Newport, UK.
Chrystalina AntoniadesNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-1192-3834
Vicky MarshallInstitute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, UK.
Luca PassamontiDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
James B RoweDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

Funding

Wellcome Trust
6 · The paper itself

Abstract

introductionProgressive 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.

Indexed as

Adrenergic Uptake InhibitorsAtomoxetine HydrochlorideCognitionNorepinephrineSupranuclear Palsy, ProgressiveAdministration, OralAgedClinical Trials, Phase II as TopicCross-Over StudiesDouble-Blind MethodFemaleHumansMaleMiddle AgedMulticenter Studies as TopicRandomized Controlled Trials as TopicAdrenergic Uptake InhibitorsAtomoxetine HydrochlorideNorepinephrineApathyAtomoxetineImpulsivityNoradrenalinePSP

Identifiers

PMID40730397
PMCPMC12306469

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.