TY - JOUR
T1 - A phase iia randomized control trial of VEL015 (sodium selenate) in mild-moderate Alzheimer's disease
AU - Malpas, Charles B.
AU - Vivasha, Lucy
AU - Genc, Sila
AU - Saling, Michael
AU - Desmond, Patricia M
AU - Steward, Christopher
AU - Hicks, Rodney John
AU - Callahan, Jason
AU - Brodtmann, Amy
AU - Collins, Steven
AU - MacFarlane, Stephen
AU - Corcoran, Niall M
AU - Hovens, Christopher M
AU - Velakoulis, Dennis
AU - O'Brien, Terence John
PY - 2016/8/23
Y1 - 2016/8/23
N2 - 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 320 βg 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 Aα1-42). 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. DiffusionMRmeasures appear to be the most sensitive biomarkers to assess disease progression over 24 weeks.
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 320 βg 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 Aα1-42). 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. DiffusionMRmeasures appear to be the most sensitive biomarkers to assess disease progression over 24 weeks.
KW - Alzheimer's disease
KW - Clinical trial
KW - Dementia
KW - Sodium selenate
UR - http://www.scopus.com/inward/record.url?scp=84984669520&partnerID=8YFLogxK
U2 - 10.3233/JAD-160544
DO - 10.3233/JAD-160544
M3 - Article
AN - SCOPUS:84984669520
SN - 1387-2877
VL - 54
SP - 223
EP - 232
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 1
ER -