Double-blind, placebo-controlled, proof-of-concept trial of bexarotene Xin moderate Alzheimer's disease.
Alzheimers Res Ther
; 8: 4, 2016 Jan 29.
Article
em En
| MEDLINE
| ID: mdl-26822146
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-ß (Aß) peptide sequences Aß1-40 and Aß1-42 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 Aß1-42 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 Aß1-42 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.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
1_ASSA2030
Base de dados:
MEDLINE
Assunto principal:
Tetra-Hidronaftalenos
/
Receptores X de Retinoides
/
Doença de Alzheimer
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Aged
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Aged80
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Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Alzheimers Res Ther
Ano de publicação:
2016
Tipo de documento:
Article