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

Mathilde M. H. Pauls, Lauren R. Binnie, Philip Benjamin, Shai Betteridge, Brian Clarke, Mohani-Preet K. Dhillon, Rita Ghatala, Fearghal A. H. Hainsworth, Franklyn A. Howe, Usman Khan, Christina Kruuse, Jeremy B. Madigan, Barry Moynihan, Bhavini Patel, Anthony C. Pereira, Egill Rostrup, Anan B. Y. Shtaya, Catherine A. Spilling, Sarah Trippier, Rebecca WilliamsRobin Young, Thomas R. Barrick, Jeremy D. Isaacs, Atticus H. Hainsworth*

*Corresponding author for this work

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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.

Original languageEnglish
JournalAlzheimer's & Dementia
Volume18
Issue number12
Pages (from-to)2393-2402
Number of pages10
ISSN1552-5260
DOIs
Publication statusPublished - 2022

Bibliographical note

Publisher Copyright:
Alzheimer's & Dementia© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

Keywords

  • cerebral blood flow
  • clinical trials
  • PDE5
  • small vessel disease
  • tadalafil
  • vascular cognitive impairment
  • vascular cognitive impairment and dementia

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