Testing the cognitive effects of tadalafil. Neuropsychological secondary outcomes from the PASTIS trial.

Clinical trials Cognitive testing Pde5 Small vessel disease Tadalafil Vascular cognitive impairment Vascular dementia

Journal

Cerebral circulation - cognition and behavior
ISSN: 2666-2450
Titre abrégé: Cereb Circ Cogn Behav
Pays: Netherlands
ID NLM: 101774849

Informations de publication

Date de publication:
2023
Historique:
received: 04 05 2023
revised: 25 09 2023
accepted: 25 09 2023
medline: 9 10 2023
pubmed: 9 10 2023
entrez: 9 10 2023
Statut: epublish

Résumé

Cerebral small vessel disease (SVD) is a major cause of cognitive impairment in older people. As secondary endpoints in a phase-2 randomised clinical trial, we tested the effects of single administration of a widely-used PDE5 inhibitor, tadalafil, on cognitive performance in older people with SVD. In a double-blinded, placebo-controlled, cross-over trial, participants received tadalafil (20 mg) and placebo on two visits ≥ 7 days apart (randomised to order of treatment). The Montreal Cognitive Assessment (MOCA) was administered at baseline, alongside a measure to estimate optimal intellectual ability (Test of Premorbid Function). Then, before and after treatment, a battery of neuropsychological tests was administered, assessing aspects of attention, information processing speed, working memory and executive function. Sixty-five participants were recruited and 55 completed the protocol ( http://www.clinicaltrials.gov. Unique identifier: NCT00123456, https://eudract.ema.europa.eu. Unique identifier: 2015-001,235-20NCT00123456.

Identifiants

pubmed: 37811523
doi: 10.1016/j.cccb.2023.100187
pii: S2666-2450(23)00031-4
pmc: PMC10550803
doi:

Types de publication

Journal Article

Langues

eng

Pagination

100187

Informations de copyright

© 2023 The Authors.

Déclaration de conflit d'intérêts

MMHP and LRB were employed as part of the PASTIS trial, JDI was Principal Investigator and AHH was Chief Investigator. CK is a PI on clinical trials funded by Bristol-Myers-Squibb and Bayer, and has received funding from NovoNordisk, all not relevant to the present trial. JDI has been a PI on clinical trials funded by Roche, Merck and Lupin Pharmaceuticals and has received funds from Nestle, Biogen and Roche, none relevant to the present trial. AHH leads MRC-Dementias Platform UK Vascular Experimental Medicine group. All other authors report no relevant disclosures. The trial was subject to an ICH-Good Clinical Practice (GCP) inspection by the UK medicines regulator, the MHRA, in September 2019, which identified a number of regulatory findings associated with the management of the trial. These are outlined in the supplementary information.

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Auteurs

Mathilde Mh Pauls (MM)

Molecular & Clinical Sciences Research Institute, St George's University of London, UK.
Department of Neurology, St George's University Hospitals NHS Foundation Trust, London, UK.

Jessica Fish (J)

Neuropsychology, St George's University Hospitals NHS Foundation Trust, London, UK.
School of Health & Wellbeing, University of Glasgow, UK.

Lauren R Binnie (LR)

Molecular & Clinical Sciences Research Institute, St George's University of London, UK.

Philip Benjamin (P)

Molecular & Clinical Sciences Research Institute, St George's University of London, UK.
Neuroradiology, St George's University Hospitals NHS Foundation Trust, London, UK.

Shai Betteridge (S)

Neuropsychology, St George's University Hospitals NHS Foundation Trust, London, UK.

Brian Clarke (B)

Department of Neurology, St George's University Hospitals NHS Foundation Trust, London, UK.

Mohani-Preet K Dhillon (MK)

Molecular & Clinical Sciences Research Institute, St George's University of London, UK.

Rita Ghatala (R)

South London Stroke Research Network, London, UK.

Fearghal Ah Hainsworth (FA)

Molecular & Clinical Sciences Research Institute, St George's University of London, UK.

Franklyn A Howe (FA)

Molecular & Clinical Sciences Research Institute, St George's University of London, UK.

Usman Khan (U)

Department of Neurology, St George's University Hospitals NHS Foundation Trust, London, UK.

Christina Kruuse (C)

Department of Neurology and Neurovascular Research Unit, Herlev Gentofte Hospital, Denmark.

Jeremy B Madigan (JB)

Neuroradiology, St George's University Hospitals NHS Foundation Trust, London, UK.

Barry Moynihan (B)

Department of Neurology, St George's University Hospitals NHS Foundation Trust, London, UK.
Department of Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.

Bhavini Patel (B)

Department of Neurology, St George's University Hospitals NHS Foundation Trust, London, UK.

Anthony C Pereira (AC)

Molecular & Clinical Sciences Research Institute, St George's University of London, UK.
Department of Neurology, St George's University Hospitals NHS Foundation Trust, London, UK.

Egill Rostrup (E)

Mental Health Centre, University of Copenhagen, Glostrup, Denmark.

Anan By Shtaya (AB)

Molecular & Clinical Sciences Research Institute, St George's University of London, UK.

Catherine A Spilling (CA)

Molecular & Clinical Sciences Research Institute, St George's University of London, UK.

Sarah Trippier (S)

South London Stroke Research Network, London, UK.

Rebecca Williams (R)

South London Stroke Research Network, London, UK.

Robin Young (R)

Robertson Centre for Biostatistics, University of Glasgow, UK.

Thomas R Barrick (TR)

Molecular & Clinical Sciences Research Institute, St George's University of London, UK.

Jeremy D Isaacs (JD)

Molecular & Clinical Sciences Research Institute, St George's University of London, UK.
Department of Neurology, St George's University Hospitals NHS Foundation Trust, London, UK.

Atticus H Hainsworth (AH)

Molecular & Clinical Sciences Research Institute, St George's University of London, UK.
Department of Neurology, St George's University Hospitals NHS Foundation Trust, London, UK.

Classifications MeSH