PMID- 27447428
OWN - NLM
STAT- MEDLINE
DCOM- 20180129
LR  - 20180131
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Linking)
VI  - 54
IP  - 1
DP  - 2016 Jul 22
TI  - A Phase IIa Randomized Control Trial of VEL015 (Sodium Selenate) in Mild-Moderate 
      Alzheimer's Disease.
PG  - 223-32
LID - 10.3233/JAD-160544 [doi]
AB  - BACKGROUND: 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. OBJECTIVE: 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. 
      METHODS: 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 
      320mug 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 
      Abeta1-42). RESULTS: 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). CONCLUSION: 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.
FAU - Malpas, Charles B
AU  - Malpas CB
AD  - Melbourne Brain Centre, The Department of Medicine, The Royal Melbourne Hospital, 
      The University of Melbourne, Melbourne, VIC, Australia.
AD  - Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, 
      VIC, Australia.
FAU - Vivash, Lucy
AU  - Vivash L
AD  - Melbourne Brain Centre, The Department of Medicine, The Royal Melbourne Hospital, 
      The University of Melbourne, Melbourne, VIC, Australia.
FAU - Genc, Sila
AU  - Genc S
AD  - Melbourne Brain Centre, The Department of Medicine, The Royal Melbourne Hospital, 
      The University of Melbourne, Melbourne, VIC, Australia.
AD  - Department of Radiology, Royal Melbourne Hospital, Melbourne, VIC, Australia.
FAU - Saling, Michael M
AU  - Saling MM
AD  - Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, 
      VIC, Australia.
AD  - Department of Neuropsychology, Austin Health, Melbourne, VIC, Australia.
AD  - Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, 
      Austin Hospital, Melbourne, VIC, Australia.
FAU - Desmond, Patricia
AU  - Desmond P
AD  - Department of Radiology, University of Melbourne, Melbourne, VIC, Australia.
AD  - Department of Radiology, Royal Melbourne Hospital, Melbourne, VIC, Australia.
FAU - Steward, Christopher
AU  - Steward C
AD  - Department of Radiology, University of Melbourne, Melbourne, VIC, Australia.
AD  - Department of Radiology, Royal Melbourne Hospital, Melbourne, VIC, Australia.
FAU - Hicks, Rodney J
AU  - Hicks RJ
AD  - Department of Radiology, University of Melbourne, Melbourne, VIC, Australia.
AD  - Centre for Molecular Imaging, Peter MacCallum Cancer Institute, Melbourne, VIC, 
      Australia.
FAU - Callahan, Jason
AU  - Callahan J
AD  - Centre for Molecular Imaging, Peter MacCallum Cancer Institute, Melbourne, VIC, 
      Australia.
FAU - Brodtmann, Amy
AU  - Brodtmann A
AD  - Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, 
      Austin Hospital, Melbourne, VIC, Australia.
AD  - Eastern Cognitive Disorders Clinic, Department of Neurology, Eastern Health, 
      Monash University, Melbourne, VIC, Australia.
FAU - Collins, Steven
AU  - Collins S
AD  - Department of Medicine, Royal Melbourne Hospital, Melbourne, VIC, Australia.
AD  - Department of Clinical Neurosciences and Neurological Research, St Vincent's 
      Hospital, Melbourne, Australia.
FAU - Macfarlane, Stephen
AU  - Macfarlane S
AD  - Caulfield Hospital, Alfred Health, Melbourne, VIC, Australia.
FAU - Corcoran, Niall M
AU  - Corcoran NM
AD  - Department of Surgery, Royal Melbourne Hospital, Melbourne, VIC, Australia.
FAU - Hovens, Christopher M
AU  - Hovens CM
AD  - Department of Surgery, Royal Melbourne Hospital, Melbourne, VIC, Australia.
FAU - Velakoulis, Dennis
AU  - Velakoulis D
AD  - Melbourne Neuropsychiatry Centre, Royal Melbourne Hospital, Melbourne, VIC, 
      Australia.
AD  - Department of Psychiatry, Melbourne, VIC, Australia.
FAU - O'Brien, Terence J
AU  - O'Brien TJ
AD  - Melbourne Brain Centre, The Department of Medicine, The Royal Melbourne Hospital, 
      The University of Melbourne, Melbourne, VIC, Australia.
AD  - Department of Medicine, Royal Melbourne Hospital, Melbourne, VIC, Australia.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Biomarkers)
RN  - 0 (MAPT protein, human)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Peptide Fragments)
RN  - 0 (amyloid beta-protein (1-42))
RN  - 0 (tau Proteins)
RN  - HV0Y51NC4J (Selenic Acid)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Alzheimer Disease/cerebrospinal fluid/diagnostic imaging/*drug therapy
MH  - Amyloid beta-Peptides/cerebrospinal fluid
MH  - Biomarkers/cerebrospinal fluid
MH  - Cognition/drug effects
MH  - Diffusion Magnetic Resonance Imaging
MH  - Double-Blind Method
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Neuroprotective Agents/adverse effects/*therapeutic use
MH  - Peptide Fragments/cerebrospinal fluid
MH  - Positron-Emission Tomography
MH  - Selenic Acid/adverse effects/*therapeutic use
MH  - Treatment Outcome
MH  - tau Proteins/cerebrospinal fluid
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - clinical trial
OT  - dementia
OT  - sodium selenate
EDAT- 2016/07/23 06:00
MHDA- 2018/01/30 06:00
CRDT- 2016/07/23 06:00
PHST- 2016/07/23 06:00 [entrez]
PHST- 2016/07/23 06:00 [pubmed]
PHST- 2018/01/30 06:00 [medline]
AID - JAD160544 [pii]
AID - 10.3233/JAD-160544 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2016 Jul 22;54(1):223-32. doi: 10.3233/JAD-160544.