The PASTIS trial: Testing tadalafil for possible use in vascular cognitive impairment
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Dokumenter
- South London Stroke Research NetworkFulltext
Forlagets udgivne version, 1,03 MB, PDF-dokument
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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Alzheimer's & Dementia |
| Vol/bind | 18 |
| Udgave nummer | 12 |
| Sider (fra-til) | 2393-2402 |
| Antal sider | 10 |
| ISSN | 1552-5260 |
| DOI | |
| Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
The authors thank our colleagues at St George's, in particular the Atkinson‐Morley Radiography team, Stroke service, South London CRN Stroke Research Network, Joint Research and Enterprise Office and Clinical Research Facility. They also acknowledge our late colleague and friend Debbie Rolfe (deceased) for her support. AHH thanks Dr. HMTC Mulrooney for helpful comments. This study was joint‐funded by UK Alzheimer's Society and Alzheimer's Drug Discovery Foundation (Grant Ref. 20140901). The funding sources had no involvement in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. The sponsor was St George's University of London (contact: sponsor@sgul.ac.uk).
Funding Information:
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 with Bristol‐Myers‐Squibb and Bayer, and has received funding from NovoNordisk, Bayer, and Bristol‐Myers‐Squibb, 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 Biogen and Roche, none relevant to the present trial. AHH has received honoraria from Eli‐Lilly and from NIA; he chairs the Vascular Cognitive Disorders PIA within ISTAART; and he 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 supporting information.
Publisher Copyright:
Alzheimer's & Dementia© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
ID: 313702946