The PASTIS trial: testing tadalafil for possible use in vascular cognitive impairment

Pauls, M. M.H. et al. (2022) The PASTIS trial: testing tadalafil for possible use in vascular cognitive impairment. Alzheimer's and Dementia, 18(12), pp. 2393-2402. (doi: 10.1002/alz.12559) (PMID:35135037)

Abstract

Introduction: There are few randomized clinical trials in vascular cognitive impairment (VCI). This trial tested the hypothesis that the PDE5 inhibitor tadalafil, a widely used vasodilator, increases cerebral blood flow (CBF) in older people with symptomatic small vessel disease, the main cause of VCI. Methods: In a double‐blind, placebo‐controlled, cross‐over trial, participants received tadalafil (20 mg) and placebo on two visits ≥7 days apart (randomized to order of treatment). The primary endpoint, change in subcortical CBF, was measured by arterial spin labelling. Results: Tadalafil increased CBF non‐significantly in all subcortical areas (N = 55, age: 66.8 (8.6) years) with greatest treatment effect within white matter hyperintensities (+9.8%, P = .0960). There were incidental treatment effects on systolic and diastolic blood pressure (–7.8, –4.9 mmHg; P < .001). No serious adverse events were observed. Discussion: This trial did not identify a significant treatment effect of single‐administration tadalafil on subcortical CBF. To detect treatment effects may require different dosing regimens.

• Item Type: Articles
• Additional Information: This study was joint-funded by UK Alzheimer's Society and Alzheimer's Drug Discovery Foundation (Grant Ref. 20140901)
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Young, Dr Robin
• Authors: Pauls, M. M.H., Binnie, L. R., Benjamin, P., Betteridge, S., Clarke, B., Dhillon, M.‐P. K., Ghatala, R., Hainsworth, F. A.H., Howe, F. A., Khan, U., Kruuse, C., Madigan, J. B., Moynihan, B., Patel, B., Pereira, A. C., Rostrup, E., Shtaya, A. B.Y., Spilling, C. A., Trippier, S., Williams, R., Young, R., Barrick, T. R., Isaacs, J. D., and Hainsworth, A. H.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Alzheimer's and Dementia
• Publisher: Wiley
• ISSN: 1552-5260
• ISSN (Online): 1552-5279
• Published Online: 08 February 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Alzheimer's and Dementia 18(12): 2393-2402
• Publisher Policy: Reproduced under a Creative Commons License