Evidence map›Paper›PMID 30530975›Full record

Trial reportJournal of Alzheimer's disease : JAD2019

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.

Martin R Farlow, Richard E Thompson, Lee-Jen Wei, Alan J Tuchman, Elaine Grenier, David Crockford, Susanne Wilke, Jeffrey Benison, Daniel L Alkon

Open access · hybridAbstract readClinical Trial, Phase IIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of Alzheimer's disease : JAD, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 2 pooled it
3.7field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

47 citing papers in PubMed, 2 syntheses or guidelines pooled it, 77 citations in OpenAlex.

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  11. The Clinical Trials Landscape for Alzheimer's Disease.CNS neuroscience & therapeutics · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 1 country.

Martin R FarlowIndiana University Medical School, Indianapolis, IN, USA.
Richard E ThompsonJohns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Lee-Jen WeiHarvard University, Boston, MA, USA.
Alan J TuchmanNew York Medical College, Valhalla, NY, USA.
Elaine GrenierNeurotrope, Inc., New York, NY, USA.
David CrockfordNeurotrope, Inc., New York, NY, USA.
Susanne WilkeNeurotrope, Inc., New York, NY, USA.
Jeffrey BenisonNeurotrope, Inc., New York, NY, USA.
Daniel L AlkonNeurotrope, Inc., New York, NY, USA.
Harvard University · USIndiana University – Purdue University Indianapolis · USJohns Hopkins University · USNew York Medical College · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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

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

methodsA 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 μg and 40 μg bryostatin, and placebo arms. The Full Analysis Set (FAS) and the Completer Analysis Set (CAS) were pre-specified alternative assessments (1-sided, p < 0.1 for primary efficacy, and 2-sided, p < 0.05 for pre-specified and post hoc exploratory analyses).

resultsThe safety profile was similar for 20 μg treatment and placebo patients. The 40 μg 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 μg bryostatin compared to placebo patients (p < 0.07). Secondary analyses at weeks 5 and 15 (i.e., 30 days post-final dosing) also favored 20 μg bryostatin compared to placebo patients. A pre-specified ANCOVA for baseline memantine blocking bryostatin and positive post-hoc trend analyses were statistically significant (2-sided, p < 0.05).

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 μg compared to the placebo cohort. These promising Phase II results support further trials of 20 μg bryostatin- without memantine- to treat AD.

Indexed as

Activities of Daily LivingAgedAged, 80 and overAlzheimer DiseaseBryostatinsCognitionDose-Response Relationship, DrugDouble-Blind MethodFemaleHumansInfusions, IntravenousMaleMental Status and Dementia TestsMiddle AgedNegative ResultsPatient DropoutsBryostatinsBryostatinmemantineneurorestorativePKC (Protein Kinase C)severe Alzheimer’s diseasesevere impairment batterysynaptic growth factorssynaptogenesis

Identifiers

PMID30530975
PMCPMC6398557
OpenAlexW2902286727

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.