TY - JOUR
T1 - Sodium selenate as a disease-modifying treatment for progressive supranuclear palsy
T2 - Protocol for a phase 2, randomised, double-blind, placebo-controlled trial
AU - Vivash, Lucy
AU - Bertram, Kelly
AU - Malpas, Charles B.
AU - Marotta, Cassandra
AU - Harding, Ian
AU - Kolbe, Scott
AU - Fielding, Joanne
AU - Clough, Meaghan
AU - Lewis, Simon John Geoffrey
AU - Tisch, Stephen
AU - Evans, Andrew H.
AU - O'Sullivan, John D
AU - Kimber, Thomas E
AU - Darby, David G.
AU - Churilov, Leonid
AU - Law, Meng
AU - Hovens, Christopher M
AU - Velakoulis, Dennis
AU - O'Brien, Terence John
N1 - Funding Information:
6ForeFront Parkinson’s Disease Research Clinic, Brain and Mind Centre, University of Sydney, Sydney, New South Wales, Australia 7Department of Neurology, St Vincent's Hospital Sydney, Darlinghurst, New South Wales, Australia 8Centre for Clinical Research, University of Queensland, Brisbane, Queensland, Australia 9Department of Neurology, Royal Brisbane & Women's Hospital, Brisbane, Queensland, Australia 10Department of Neurology, Royal Adelaide Hospital, Adelaide, South Australia, Australia 11The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia 12Eastern Cognitive Disorders Clinic, Box Hill Hospital, Melbourne, Victoria, Australia 13Department of Radiology, Alfred Hospital, Melbourne, Victoria, Australia 14Department of Surgery, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia 15Department of Neuropsychiatry, Royal Melbourne Hospital, Parkville, Victoria, Australia 16Melbourne Neuropsychiatry Centre, University of Melbourne, Parkville, Victoria, Australia Contributors LV drafted the manuscript. LV, KLB, CMalpas, CMarotta, IHH, SK, JF, MC, SJGL, ST, AHE, JDOS, TK, LC, DD, ML, CMH, DV and TJOB contributed to the study design. All authors edited the manuscript and approved the final version. Funding This work is supported by the Australian National Health and Medical Research Council (NHMRC) Medical Research Future Fund grant number GNT1200254. TJOB is supported by an NHMRC Investigator Grant (APP1176426). SJGL is supported by NHMRC Leadership Fellowship (#1195830). Competing interests All authors report a grant from the NHMRC to support this study. The authors report the following disclosures outside of this study: LV reports personal fees from Biogen Australia, and research funding from Biogen, Eisai and LMI. AHE reports honoraria for presentations from Merck, Allergan, Ipsen, Teva, UCB, Abbott, AbbVie, STADA, participation in scientific advisory board meetings with Allergan, AbbVie, Ipsen and STADA and shares in GKC and CSL. DD reports consultancy fees from Biogen, Novartis. KLB, CMalpas, CMarotta, IHH, SK, JF, MC, SJGL, ST, JDOS, TK, LC, ML, CMH and DV report no disclosures. Patient consent for publication Not applicable.
Funding Information:
This is a multi-site, phase 2, double-blind, randomised, placebo-controlled trial to assess the safety and efficacy of sodium selenate as a treatment for PSP (RS). Participants will receive either sodium selenate (15 mg, three times a day) or placebo for 52 weeks. Seventy patients will be recruited in to this study. The study will be conducted at six centres in Melbourne, Sydney, Brisbane and Adelaide. The study is funded by the Australian Medical Research Future Fund (GNT1200254). Ethics approval was granted by Alfred Health Human Research Ethics Committee, Melbourne (594/20). The trial is registered with the ANZCTR (ACTRN12620001254987). The study commenced recruitment in July 2021 and is anticipated to complete (last patient last visit) in March 2025.
Publisher Copyright:
©
PY - 2021/12
Y1 - 2021/12
N2 - 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).
AB - 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).
KW - clinical trials
KW - neurology
KW - Parkinson's disease
UR - http://www.scopus.com/inward/record.url?scp=85122518956&partnerID=8YFLogxK
U2 - 10.1136/bmjopen-2021-055019
DO - 10.1136/bmjopen-2021-055019
M3 - Article
C2 - 34916328
AN - SCOPUS:85122518956
SN - 2044-6055
VL - 11
JO - BMJ Open
JF - BMJ Open
IS - 12
M1 - e055019
ER -