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

ABSTRACT: We 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.Twenty 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 ?4 (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-? (A?) peptide sequences A?1-40 and A?1-42 measurements were collected as biomarker outcomes.There 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 A?1-42 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.The primary outcome of this trial was negative. The data suggest that bexarotene reduced brain amyloid and increased serum A?1-42 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.ClinicalTrials.gov identifier NCT01782742 . Registered 29 January 2013.

SUBMITTER: Cummings JL

PROVIDER: S-EPMC4731943 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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

Cummings Jeffrey L JL Zhong Kate K Kinney Jefferson W JW Heaney Chelcie C Moll-Tudla Joanne J Joshi Abhinay A Pontecorvo Michael M Devous Michael M Tang Anne A Bena James J

Alzheimer's research & therapy 20160129

<h4>Background</h4>We 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.<h4>Methods</h4>Twenty 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 prespeci ...[more]

PMID: 26822146

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

Publications

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

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