Dataset Information

A Randomized, Double-Blind, Placebo-Controlled, Phase II Study Assessing Safety, Tolerability, and Efficacy of Bryostatin in the Treatment of Moderately Severe to Severe Alzheimer's Disease.

ABSTRACT:

Background

Bryostatin-activated PKC epsilon pre-clinically induces synaptogenesis, anti-apoptosis, anti-amyloid-? oligomers, and anti-hyperphosphorylated tau.

Objectives

To investigate bryostatin safety, tolerability, and efficacy to improve cognition in advanced Alzheimer's disease (AD) patients.

Methods

A double-blind, randomized, placebo-controlled Phase II, 12-week trial of i.v. bryostatin for 150 advanced AD patients (55-85) with MMSE-2 of 4-15, randomized 1:1:1 into 20 ?g and 40 ?g bryostatin, and placebo arms. The Full Analysis Set (FAS) and the Completer Analysis Set (CAS) were pre-specified alternative assessments (1-sided, p?ResultsThe safety profile was similar for 20 ?g treatment and placebo patients. The 40 ?g patients showed safety and drop-out issues, but no efficacy. Primary improvement of Severe Impairment Battery (SIB) scores at 13 weeks was not significant (p?=?0.134) in the FAS, although in the CAS, the SIB comparison favored 20 ?g bryostatin compared to placebo patients (p?ConclusionAlthough the primary endpoint was not significant in the FAS, primary and secondary analyses in the CAS, and pre-specified and post-hoc exploratory analyses did favor bryostatin 20 ?g compared to the placebo cohort. These promising Phase II results support further trials of 20 ?g bryostatin- without memantine- to treat AD.

SUBMITTER: Farlow MR

PROVIDER: S-EPMC6398557 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

A Randomized, Double-Blind, Placebo-Controlled, Phase II Study Assessing Safety, Tolerability, and Efficacy of Bryostatin in the Treatment of Moderately Severe to Severe Alzheimer's Disease.

Farlow Martin R MR Thompson Richard E RE Wei Lee-Jen LJ Tuchman Alan J AJ Grenier Elaine E Crockford David D Wilke Susanne S Benison Jeffrey J Alkon Daniel L DL

Journal of Alzheimer's disease : JAD 20190101 2

<h4>Background</h4>Bryostatin-activated PKC epsilon pre-clinically induces synaptogenesis, anti-apoptosis, anti-amyloid-β oligomers, and anti-hyperphosphorylated tau.<h4>Objectives</h4>To investigate bryostatin safety, tolerability, and efficacy to improve cognition in advanced Alzheimer's disease (AD) patients.<h4>Methods</h4>A double-blind, randomized, placebo-controlled Phase II, 12-week trial of i.v. bryostatin for 150 advanced AD patients (55-85) with MMSE-2 of 4-15, randomized 1:1:1 into 2 ...[more]

PMID: 30530975

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Dataset Information

A Randomized, Double-Blind, Placebo-Controlled, Phase II Study Assessing Safety, Tolerability, and Efficacy of Bryostatin in the Treatment of Moderately Severe to Severe Alzheimer's Disease.

Background

Objectives

Methods

Publications

A Randomized, Double-Blind, Placebo-Controlled, Phase II Study Assessing Safety, Tolerability, and Efficacy of Bryostatin in the Treatment of Moderately Severe to Severe Alzheimer's Disease.

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