Sodium selenate as a disease-modifying treatment for progressive supranuclear palsy: protocol for a phase 2, randomised, double-blind, placebo-controlled trial
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 a...
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BMJ Publishing Group
2021-12-01
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| author | Kelly L Bertram Lucy Vivash Dennis Velakoulis Leonid Churilov Thomas Kimber David Darby Terence J O’Brien Charles B Malpas Christopher M Hovens Simon J G Lewis Joanne Fielding Andrew H Evans Stephen Tisch John D O’Sullivan Ian H Harding Meaghan Clough Cassandra Marotta Scott Kolbe Meng Law |
| author_facet | Kelly L Bertram Lucy Vivash Dennis Velakoulis Leonid Churilov Thomas Kimber David Darby Terence J O’Brien Charles B Malpas Christopher M Hovens Simon J G Lewis Joanne Fielding Andrew H Evans Stephen Tisch John D O’Sullivan Ian H Harding Meaghan Clough Cassandra Marotta Scott Kolbe Meng Law |
| author_sort | Kelly L Bertram |
| collection | DOAJ |
| 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 representative and their study partner will provide written informed consent at trial commencement. The results of the study will be presented at national and international conferences and published in peer-reviewed journals.Trial registration number Australian New Zealand Clinical Trials Registry (ACTRN12620001254987). |
| format | Article |
| id | doaj-art-3a87c0246a7c43bca2eb38c193c2d256 |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2021-12-01 |
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| spelling | doaj-art-3a87c0246a7c43bca2eb38c193c2d2562024-12-10T09:15:09ZengBMJ Publishing GroupBMJ Open2044-60552021-12-01111210.1136/bmjopen-2021-055019Sodium selenate as a disease-modifying treatment for progressive supranuclear palsy: protocol for a phase 2, randomised, double-blind, placebo-controlled trialKelly L Bertram0Lucy Vivash1Dennis Velakoulis2Leonid Churilov3Thomas Kimber4David Darby5Terence J O’Brien6Charles B Malpas7Christopher M Hovens8Simon J G Lewis9Joanne Fielding10Andrew H Evans11Stephen Tisch12John D O’Sullivan13Ian H Harding14Meaghan Clough15Cassandra Marotta16Scott Kolbe17Meng Law18Monash University Central Clinical School, Melbourne, Victoria, AustraliaMonash University Central Clinical School, Melbourne, Victoria, Australia15Melbourne Neuropsychiatry Centre, North West Mental Health and The University of Melbourne, Melbourne, Australia7 Medicine, The University of Melbourne, Melbourne, Victoria, Australia6Royal Adelaide Hospital, Adelaide, SA, Australia2 Neurology Department, Florey Institute of Neuroscience and Mental Health—Austin Campus, Heidelberg, Victoria, AustraliaMonash University Central Clinical School, Melbourne, Victoria, Australia1 Melbourne School of Psychological Sciences, The University of Melbourne, Melbourne, Victoria, AustraliaDepartment of Surgery, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, AustraliaForeFront Parkinson’s Disease Research Clinic, Brain and Mind Centre, University of Sydney, Sydney, New South Wales, Australia2Department of Neuroscience, Central Clinical School, Faculty of Medicine, Nursing and Health Science, Monash University, Melbourne, VIC, AustraliaDepartment of Neurology, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, AustraliaDepartment of Neurology, St Vincent`s Health Australia Ltd, Sydney, New South Wales, Australia1Royal Brisbane and Women’s Hospital, Herston, QLD, AustraliaMonash University Central Clinical School, Melbourne, Victoria, AustraliaDepartment of Neurosciences, Monash University, Melbourne, Victoria, Australia1Central Clinical School, Monash University, Melbourne, VIC, AustraliaDepartment of Neurosciences, Monash University, Melbourne, Victoria, Australia2Department of Neurosciences, Monash University, Melbourne, VIC, AustraliaIntroduction 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 representative and their study partner will provide written informed consent at trial commencement. The results of the study will be presented at national and international conferences and published in peer-reviewed journals.Trial registration number Australian New Zealand Clinical Trials Registry (ACTRN12620001254987).https://bmjopen.bmj.com/content/11/12/e055019.full |
| spellingShingle | Kelly L Bertram Lucy Vivash Dennis Velakoulis Leonid Churilov Thomas Kimber David Darby Terence J O’Brien Charles B Malpas Christopher M Hovens Simon J G Lewis Joanne Fielding Andrew H Evans Stephen Tisch John D O’Sullivan Ian H Harding Meaghan Clough Cassandra Marotta Scott Kolbe Meng Law Sodium selenate as a disease-modifying treatment for progressive supranuclear palsy: protocol for a phase 2, randomised, double-blind, placebo-controlled trial BMJ Open |
| title | Sodium selenate as a disease-modifying treatment for progressive supranuclear palsy: protocol for a phase 2, randomised, double-blind, placebo-controlled trial |
| title_full | Sodium selenate as a disease-modifying treatment for progressive supranuclear palsy: protocol for a phase 2, randomised, double-blind, placebo-controlled trial |
| title_fullStr | Sodium selenate as a disease-modifying treatment for progressive supranuclear palsy: protocol for a phase 2, randomised, double-blind, placebo-controlled trial |
| title_full_unstemmed | Sodium selenate as a disease-modifying treatment for progressive supranuclear palsy: protocol for a phase 2, randomised, double-blind, placebo-controlled trial |
| title_short | Sodium selenate as a disease-modifying treatment for progressive supranuclear palsy: protocol for a phase 2, randomised, double-blind, placebo-controlled trial |
| title_sort | sodium selenate as a disease modifying treatment for progressive supranuclear palsy protocol for a phase 2 randomised double blind placebo controlled trial |
| url | https://bmjopen.bmj.com/content/11/12/e055019.full |
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