title: A Phase IIa Randomized Control Trial of VEL015 (Sodium Selenate) in Mild-Moderate Alzheimer's Disease.
abstract: There is increasing interest in targeting hyperphosphorylated tau (h-tau) as a disease modifying approach for Alzheimer's disease (AD). Sodium selenate directly stimulates the activity of PP2A, the main enzyme responsible for h-tau dephosphorylation in the brain.
  
  
  
  This study assessed the safety and tolerability of 24-week treatment with VEL015 (sodium selenate) in AD. Investigating the effects of VEL015 on cognitive, CSF, and neuroimaging biomarkers of AD were secondary, exploratory objectives. Data were used to identify biomarkers showing most promise for use in subsequent efficacy trials.
  
  
  
  A 24-week, multicenter, Phase IIa, double-blinded randomized controlled trial. Forty patients aged ≥55 y with mild-moderate AD (MMSE 14-26) were randomized to supranutritional (VEL015 10 mg tds [n = 20]) and control (VEL015 320μg tds [n = 10] or placebo [n = 10]) groups. Patients were regularly monitored for safety, adverse events (AEs), and protocol compliance. Exploratory biomarkers included cognitive tests, neuroimaging (diffusion MR), and CSF (p-tau, t-tau, and Aβ1-42).
  
  
  
  Thirty-six (90%; [supranutritional n = 18, control/placebo n = 18]) patients completed the trial. There were no differences in the incidence of specific AEs between groups. Only one secondary biomarker, diffusion MR measures, showed group differences, with less deterioration in the supranutritional group (p < 0.05).
  
  
  
  Treatment with VEL015 at doses up to 30 mg per day for 24 weeks was safe and well-tolerated in patients with AD. Diffusion MR measures appear to be the most sensitive biomarkers to assess disease progression over 24 weeks.
authors.affiliation: Melbourne Brain Centre, The Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC, Australia.|Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Charles B
authors.initials: CB
authors.lastname: Malpas
authors.affiliation: Melbourne Brain Centre, The Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Lucy
authors.initials: L
authors.lastname: Vivash
authors.affiliation: Melbourne Brain Centre, The Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC, Australia.|Department of Radiology, Royal Melbourne Hospital, Melbourne, VIC, Australia.
authors.forename: Sila
authors.initials: S
authors.lastname: Genc
authors.affiliation: Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, VIC, Australia.|Department of Neuropsychology, Austin Health, Melbourne, VIC, Australia.|Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, Austin Hospital, Melbourne, VIC, Australia.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Saling
authors.affiliation: Department of Radiology, University of Melbourne, Melbourne, VIC, Australia.|Department of Radiology, Royal Melbourne Hospital, Melbourne, VIC, Australia.
authors.forename: Patricia
authors.initials: P
authors.lastname: Desmond
authors.affiliation: Department of Radiology, University of Melbourne, Melbourne, VIC, Australia.|Department of Radiology, Royal Melbourne Hospital, Melbourne, VIC, Australia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Steward
authors.affiliation: Department of Radiology, University of Melbourne, Melbourne, VIC, Australia.|Centre for Molecular Imaging, Peter MacCallum Cancer Institute, Melbourne, VIC, Australia.
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Hicks
authors.affiliation: Centre for Molecular Imaging, Peter MacCallum Cancer Institute, Melbourne, VIC, Australia.
authors.forename: Jason
authors.initials: J
authors.lastname: Callahan
authors.affiliation: Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, Austin Hospital, Melbourne, VIC, Australia.|Eastern Cognitive Disorders Clinic, Department of Neurology, Eastern Health, Monash University, Melbourne, VIC, Australia.
authors.forename: Amy
authors.initials: A
authors.lastname: Brodtmann
authors.affiliation: Department of Medicine, Royal Melbourne Hospital, Melbourne, VIC, Australia.|Department of Clinical Neurosciences and Neurological Research, St Vincent's Hospital, Melbourne, Australia.
authors.forename: Steven
authors.initials: S
authors.lastname: Collins
authors.affiliation: Caulfield Hospital, Alfred Health, Melbourne, VIC, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Macfarlane
authors.affiliation: Department of Surgery, Royal Melbourne Hospital, Melbourne, VIC, Australia.
authors.forename: Niall M
authors.initials: NM
authors.lastname: Corcoran
authors.affiliation: Department of Surgery, Royal Melbourne Hospital, Melbourne, VIC, Australia.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Hovens
authors.affiliation: Melbourne Neuropsychiatry Centre, Royal Melbourne Hospital, Melbourne, VIC, Australia.|Department of Psychiatry, Melbourne, VIC, Australia.
authors.forename: Dennis
authors.initials: D
authors.lastname: Velakoulis
authors.affiliation: Melbourne Brain Centre, The Department of Medicine, The Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC, Australia.|Department of Medicine, Royal Melbourne Hospital, Melbourne, VIC, Australia.
authors.forename: Terence J
authors.initials: TJ
authors.lastname: O'Brien
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003071:Cognition / Q000187:drug effects; D038524:Diffusion Magnetic Resonance Imaging; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D049268:Positron-Emission Tomography; D064586:Selenic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; C054369:MAPT protein, human; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D064586:Selenic Acid
keywords: Alzheimer’s disease; clinical trial; dementia; sodium selenate