| Title: |
Sodium selenate as a disease-modifying treatment for progressive supranuclear palsy: Protocol for a phase 2, randomised, double-blind, placebo-controlled trial |
| Authors: |
Vivash, L; Bertram, KL; Malpas, CB; Marotta, C; Harding, IH; Kolbe, S; Fielding, J; Clough, M; Lewis, SJG; Tisch, S; Evans, AH; O'Sullivan, JD; Kimber, T; Darby, D; Churilov, L; Law, M; Hovens, CM; Velakoulis, D; O'Brien, TJ |
| Publisher Information: |
BMJ PUBLISHING GROUP |
| Publication Year: |
2021 |
| Collection: |
The University of Melbourne: Digital Repository |
| Description: |
INTRODUCTION: Progressive supranuclear palsy (PSP) is a neurodegenerative disorder for which there are currently no disease-modifying therapies. The neuropathology of PSP is associated with the accumulation of hyperphosphorylated tau in the brain. We have previously shown that protein phosphatase 2 activity in the brain is upregulated by sodium selenate, which enhances dephosphorylation. Therefore, the objective of this study is to evaluate the efficacy and safety of sodium selenate as a disease-modifying therapy for PSP. METHODS AND ANALYSIS: This will be a multi-site, phase 2b, double-blind, placebo-controlled trial of sodium selenate. 70 patients will be recruited at six Australian academic hospitals and research institutes. Following the confirmation of eligibility at screening, participants will be randomised (1:1) to receive 52 weeks of active treatment (sodium selenate; 15 mg three times a day) or matching placebo. Regular safety and efficacy visits will be completed throughout the study period. The primary study outcome is change in an MRI volume composite (frontal lobe+midbrain-3rd ventricle) over the treatment period. Analysis will be with a general linear model (GLM) with the MRI composite at 52 weeks as the dependent variable, treatment group as an independent variable and baseline MRI composite as a covariate. Secondary outcomes are change in PSP rating scale, clinical global impression of change (clinician) and change in midbrain mean diffusivity. These outcomes will also be analysed with a GLM as above, with the corresponding baseline measure entered as a covariate. Secondary safety and tolerability outcomes are frequency of serious adverse events, frequency of down-titration occurrences and frequency of study discontinuation. Additional, as yet unplanned, exploratory outcomes will include analyses of other imaging, cognitive and biospecimen measures. ETHICS AND DISSEMINATION: The study was approved by the Alfred Health Ethics Committee (594/20). Each participant or their legally authorised ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
2044-6055 |
| Relation: |
https://hdl.handle.net/11343/296137 |
| Availability: |
https://hdl.handle.net/11343/296137 |
| Rights: |
https://creativecommons.org/licenses/by-nc/4.0 ; CC BY-NC |
| Accession Number: |
edsbas.F29096B3 |
| Database: |
BASE |