A Phase IIa Randomized Control Trial of VEL015 (Sodium Selenate) in Mild-Moderate Alzheimer's Disease.

Abstract

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 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).

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.

• Authors: Charles B Malpas, Lucy Vivash, Sila Genc, Michael M Saling, Patricia Desmond, Christopher Steward, Rodney J Hicks, Jason Callahan, Amy Brodtmann, Steven Collins, Stephen Macfarlane, Niall M Corcoran, Christopher M Hovens, Dennis Velakoulis, Terence J O'Brien
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 54 Issue 1 Pg. 223-32 (07 22 2016) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 27447428 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Biomarkers
• MAPT protein, human
• Neuroprotective Agents
• Peptide Fragments
• amyloid beta-protein (1-42)
• tau Proteins
• Selenic Acid

Topics

• Aged
• Aged, 80 and over
• Alzheimer Disease (cerebrospinal fluid, diagnostic imaging, drug therapy)
• Amyloid beta-Peptides (cerebrospinal fluid)
• Biomarkers (cerebrospinal fluid)
• Cognition (drug effects)
• Diffusion Magnetic Resonance Imaging
• Double-Blind Method
• Female
• Follow-Up Studies
• Humans
• Male
• Middle Aged
• Neuroprotective Agents (adverse effects, therapeutic use)
• Peptide Fragments (cerebrospinal fluid)
• Positron-Emission Tomography
• Selenic Acid (adverse effects, therapeutic use)
• Treatment Outcome
• tau Proteins (cerebrospinal fluid)