Evidence map›Paper›PMID 38273408›Full record

Trial reportAlzheimer's research & therapy2024

A pilot study to evaluate the effect of CT1812 treatment on synaptic density and other biomarkers in Alzheimer's disease.

Christopher H van Dyck, Adam P Mecca, Ryan S O'Dell, Hugh H Bartlett, Nina G Diepenbrock, Yiyun Huang, Mary E Hamby, Michael Grundman, Susan M Catalano, Anthony O Caggiano and 1 more

Registry-linked trialOpen access · goldAbstract readRandomized Controlled TrialClinical Trial, Phase IClinical Trial, Phase II
In one paragraph

Trial report in Alzheimer's research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03493282 (A Pilot Synaptic Vesicle Glycoprotein 2A), which is not on this map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
4.9field-weighted citation impact, top 4% 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.

NCT03493282 phase1 / phase2completednot on this map

A Pilot Synaptic Vesicle Glycoprotein 2A (SV2A) PET Study to Evaluate the Effect of CT1812 Treatment on Synaptic Density in Participants With Mild to Moderate Alzheimer's Disease

TypeinterventionalSponsorCognition TherapeuticsRan2018 to 2020Enrolled43ConditionsAlzheimer DiseaseArmsActive Treatment- CT1812 100 mg, Active Treatment- CT1812 300 mg, Placebo
3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Phase 2 study of zervimesine (CT1812) in participants with mild-to-moderate dementia with Lewy bodies (DLB).Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Trial
  4. Article
  5. Review
  6. The roles of biomarkers in Alzheimer's disease clinical trials.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Review
  7. Article
  8. Review
  9. Review
  10. Review
  11. The Clinical Trials Landscape for Alzheimer's Disease.CNS neuroscience & therapeutics · 2025
    Review
  12. Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. Review
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

11 authors at 3 institutions in 1 country.

Christopher H van DyckAlzheimer's Disease Research Unit, Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. christopher.vandyck@yale.edu.
Adam P MeccaAlzheimer's Disease Research Unit, Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Ryan S O'DellAlzheimer's Disease Research Unit, Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Hugh H BartlettAlzheimer's Disease Research Unit, Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Nina G DiepenbrockAlzheimer's Disease Research Unit, Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Yiyun HuangDepartment of Radiology and Biomedical Imaging, Yale University, New Haven, CT, USA.
Mary E HambyCognition Therapeutics Inc., Pittsburgh, PA, USA.
Michael GrundmanGlobal R&D Partners, LLC, San Diego, CA, USA.
Susan M CatalanoCircle Biopharma, Pittsburgh, PA, USA.
Anthony O CaggianoCognition Therapeutics Inc., Pittsburgh, PA, USA. acaggiano@cogrx.com.
Richard E CarsonDepartment of Radiology and Biomedical Imaging, Yale University, New Haven, CT, USA.
Yale University · USCognition Therapeutics (United States) · USUniversity of California San Diego · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Yale Alzheimer Disease Research CenterP30AG066508 · NIA · YALE UNIVERSITY · PI STEPHEN M STRITTMATTER · 2020 to 2026
$30.2M
A Pilot Synaptic Vesicle Glycoprotein 2A (SV2A) PET Study to Evaluate the Effect of CT1812 Treatment on Synaptic Density in Subjects with Mild to Moderate Alzheimer's DiseaseRF1AG057553 · NIA · COGNITION THERAPEUTICS, INC. · PI CATALANO, SUSAN M · 2017 to 2020
$4.8M
NCATS NIH HHS UL1 TR001863NIA NIH HHS AG057553NIA NIH HHS P30 AG066508NIA NIH HHS RF1 AG057553
6 · The paper itself

Abstract

backgroundEffective, disease-modifying therapeutics for the treatment of Alzheimer's disease (AD) remain a large unmet need. Extensive evidence suggests that amyloid beta (Aβ) is central to AD pathophysiology, and Aβ oligomers are among the most toxic forms of Aβ. CT1812 is a novel brain penetrant sigma-2 receptor ligand that interferes with the binding of Aβ oligomers to neurons. Preclinical studies of CT1812 have demonstrated its ability to displace Aβ oligomers from neurons, restore synapses in cell cultures, and improve cognitive measures in mouse models of AD. CT1812 was found to be generally safe and well tolerated in a placebo-controlled phase 1 clinical trial in healthy volunteers and phase 1a/2 clinical trials in patients with mild to moderate dementia due to AD. The unique objective of this study was to incorporate synaptic positron emission tomography (PET) imaging as an outcome measure for CT1812 in AD patients.

methodsThe present phase 1/2 study was a randomized, double-blind, placebo-controlled, parallel-group trial conducted in 23 participants with mild to moderate dementia due to AD to primarily evaluate the safety of CT1812 and secondarily its pharmacodynamic effects. Participants received either placebo or 100 mg or 300 mg per day of oral CT1812 for 24 weeks. Pharmacodynamic effects were assessed using the exploratory efficacy endpoints synaptic vesicle glycoprotein 2A (SV2A) PET, fluorodeoxyglucose (FDG) PET, volumetric MRI, cognitive clinical measures, as well as cerebrospinal fluid (CSF) biomarkers of AD pathology and synaptic degeneration.

resultsNo treatment differences relative to placebo were observed in the change from baseline at 24 weeks in either SV2A or FDG PET signal, the cognitive clinical rating scales, or in CSF biomarkers. Composite region volumetric MRI revealed a trend towards tissue preservation in participants treated with either dose of CT1812, and nominally significant differences with both doses of CT1812 compared to placebo were found in the pericentral, prefrontal, and hippocampal cortices. CT1812 was safe and well tolerated.

conclusionsThe safety findings of this 24-week study and the observed changes on volumetric MRI with CT1812 support its further clinical development.

trial registrationThe clinical trial described in this manuscript is registered at clinicaltrials.gov (NCT03493282).

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAnimalsBiomarkersFluorodeoxyglucose F18HumansMicePilot ProjectsPositron-Emission TomographyAmyloid beta-PeptidesBiomarkersFluorodeoxyglucose F18Alzheimer’s diseaseAmyloid beta oligomersBiomarkersFDG PETSigma-2 receptorSV2A PET

Identifiers

PMID38273408
PMCPMC10809445
OpenAlexW4391229840

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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.