Evidence map›Paper›PMID 26822146›Full record

Trial reportAlzheimer's research & therapy2016

Double-blind, placebo-controlled, proof-of-concept trial of bexarotene Xin moderate Alzheimer's disease.

Jeffrey L Cummings, Kate Zhong, Jefferson W Kinney, Chelcie Heaney, Joanne Moll-Tudla, Abhinay Joshi, Michael Pontecorvo, Michael Devous, Anne Tang, James Bena

Registry-linked trialOpen access · goldAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Alzheimer's research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01782742 (A Double Blind Placebo Controlled Randomized Study to Evaluate the Efficacy and Safety of Bexarotene in Patients With Mild to Moderate Alzheimer's Disease), which is not on this map. Cited by 113 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
113citing papers in PubMed, 3 pooled it
11.3field-weighted citation impact, top 1% 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.

NCT01782742 phase2completednot on this map

A Double Blind Placebo Controlled Randomized Study to Evaluate the Efficacy and Safety of Bexarotene in Patients With Mild to Moderate Alzheimer's Disease

TypeinterventionalSponsorThe Cleveland ClinicRan2013 to 2014Enrolled20ConditionsAlzheimer's DiseaseArmsBexarotene, Placebo
3 · Its place in the literature

Who cites it

113 citing papers in PubMed, 3 syntheses or guidelines pooled it, 187 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Retinoic acid in health and disease.Signal transduction and targeted therapy · 2026
    Review
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  13. APOE-Targeted Therapeutics for Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Review
  14. Development of a web platform to advance data-driven recruitment for ADRD research.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  15. Review
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53 more citing papers are in PubMed but not listed here.

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

10 authors at 3 institutions in 1 country.

Jeffrey L CummingsCleveland Clinic Lou Ruvo Center for Brain Health, 888 West Bonneville Avenue, Las Vegas, NV, 89106, USA. cumminj@ccf.org.
Kate ZhongCleveland Clinic Lou Ruvo Center for Brain Health, 888 West Bonneville Avenue, Las Vegas, NV, 89106, USA. zhongk@ccf.org.
Jefferson W KinneyDepartment of Psychology, University of Nevada, Las Vegas, NV, USA. jefferson.kinney@unlv.edu.
Chelcie HeaneyDepartment of Psychology, University of Nevada, Las Vegas, NV, USA. chelcie.heaney@gmail.com.
Joanne Moll-TudlaCleveland Clinic Lou Ruvo Center for Brain Health, 888 West Bonneville Avenue, Las Vegas, NV, 89106, USA. mollj@ccf.org.
Abhinay JoshiAvid Pharmaceuticals, Philadelphia, PA, USA. joshi@avidrp.com.
Michael PontecorvoAvid Pharmaceuticals, Philadelphia, PA, USA. pontecorvo@avidrp.com.
Michael DevousAvid Pharmaceuticals, Philadelphia, PA, USA. devous@avidrp.com.
Anne TangCleveland Clinic Quantitative Health Services, Cleveland, OH, USA. tanga@ccf.org.
James BenaCleveland Clinic Quantitative Health Services, Cleveland, OH, USA. benaj@ccf.org.
Cleveland Clinic · USUniversity of Nevada, Las Vegas · USLou Ruvo Brain Institute · US

Funding

Renewal of Centers of Biomedical Research Excellence (COBRE) (Phase 2) CNTN - ResubmissionP20GM109025 · NIGMS · CLEVELAND CLINIC FOUNDATION · PI JESSICA KIRKLAND CALDWELL · 2015 to 2026
$22.8M
NIGMS NIH HHS P20 GM109025
6 · The paper itself

Abstract

backgroundWe assessed the impact of retinoid X receptor (RXR) agonist bexarotene on brain amyloid measured by amyloid imaging in patients with Alzheimer's disease (AD) in a proof-of-concept trial.

methodsTwenty patients with AD [Mini Mental State Examination (MMSE) score 10-20 inclusive] with positive florbetapir scans were randomized to receive 300 mg of bexarotene or placebo for 4 weeks. The amyloid imaging result was the primary outcome. Whole-population analyses and prespecified analyses by genotype [apolipoprotein E ε4 (ApoE4) carriers and ApoE4 noncarriers] were conducted. Secondary outcomes included scores on the Alzheimer's Disease Assessment Scale-Cognitive subscale, Alzheimer's Disease Cooperative Study-Activities of Daily Living scale, MMSE, Clinical Dementia Rating scale, and Neuropsychiatric Inventory. Serum amyloid-β (Aβ) peptide sequences Aβ1-40 and Aβ1-42 measurements were collected as biomarker outcomes.

resultsThere was no change in the composite or regional amyloid burden when all patients were included in the analysis. ApoE4 noncarriers showed a significant reduction in brain amyloid on the composite measure in five of six regional measurements. No change in amyloid burden was observed in ApoE4 carriers. There was a significant association between increased serum Aβ1-42 and reductions in brain amyloid in ApoE4 noncarriers (not in carriers). There were significant elevations in serum triglycerides in bexarotene-treated patients. There was no consistent change in any clinical measure.

conclusionsThe primary outcome of this trial was negative. The data suggest that bexarotene reduced brain amyloid and increased serum Aβ1-42 in ApoE4 noncarriers. Elevated triglycerides could represent a cardiovascular risk, and bexarotene should not be administered outside a research setting. RXR agonists warrant further investigations as AD therapies.

trial registrationClinicalTrials.gov identifier NCT01782742 . Registered 29 January 2013.

Indexed as

AgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesApolipoproteins EBexaroteneDouble-Blind MethodFemaleHumansMaleMiddle AgedPeptide FragmentsPositron-Emission TomographyRetinoid X ReceptorsTetrahydronaphthalenesTreatment OutcomeAmyloid beta-Peptidesamyloid beta-protein (1-40)amyloid beta-protein (1-42)Apolipoproteins EBexarotenePeptide FragmentsRetinoid X ReceptorsTetrahydronaphthalenes

Identifiers

PMID26822146
PMCPMC4731943
OpenAlexW2272900632

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.