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- Title
Double-blind, placebo-controlled, proof-of-concept trial of bexarotene Xin moderate Alzheimer's disease.
- Authors
Cummings, Jeffrey L.; Kate Zhong; Kinney, Jefferson W.; Heaney, Chelcie; Moll-Tudla, Joanne; Joshi, Abhinay; Pontecorvo, Michael; Devous, Michael; Tang, Anne; Bena, James
- Abstract
Background: 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. Methods: 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 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. Results: 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 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. Conclusions: The 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 registration: ClinicalTrials.gov identifier NCT01782742. Registered 29 January 2013.
- Subjects
RETINOID X receptors; AMYLOID beta-protein; ALZHEIMER'S disease risk factors; APOLIPOPROTEIN E analysis; PEPTIDE antibiotics
- Publication
Alzheimer's Research & Therapy, 2016, Vol 8, p1
- ISSN
1758-9193
- Publication type
Article
- DOI
10.1186/s13195-016-0173-2