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A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease

OBJECTIVE: A randomized, placebo-controlled, double-blind, multicenter 52-week phase 2 trial of resveratrol in individuals with mild to moderate Alzheimer disease (AD) examined its safety and tolerability and effects on biomarker (plasma Aβ40 and Aβ42, CSF Aβ40, Aβ42, tau, and phospho-tau 181) and v...

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Autores principales: Turner, R. Scott, Thomas, Ronald G., Craft, Suzanne, van Dyck, Christopher H., Mintzer, Jacobo, Reynolds, Brigid A., Brewer, James B., Rissman, Robert A., Raman, Rema, Aisen, Paul S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626244/
https://www.ncbi.nlm.nih.gov/pubmed/26362286
http://dx.doi.org/10.1212/WNL.0000000000002035
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author Turner, R. Scott
Thomas, Ronald G.
Craft, Suzanne
van Dyck, Christopher H.
Mintzer, Jacobo
Reynolds, Brigid A.
Brewer, James B.
Rissman, Robert A.
Raman, Rema
Aisen, Paul S.
author_facet Turner, R. Scott
Thomas, Ronald G.
Craft, Suzanne
van Dyck, Christopher H.
Mintzer, Jacobo
Reynolds, Brigid A.
Brewer, James B.
Rissman, Robert A.
Raman, Rema
Aisen, Paul S.
author_sort Turner, R. Scott
collection PubMed
description OBJECTIVE: A randomized, placebo-controlled, double-blind, multicenter 52-week phase 2 trial of resveratrol in individuals with mild to moderate Alzheimer disease (AD) examined its safety and tolerability and effects on biomarker (plasma Aβ40 and Aβ42, CSF Aβ40, Aβ42, tau, and phospho-tau 181) and volumetric MRI outcomes (primary outcomes) and clinical outcomes (secondary outcomes). METHODS: Participants (n = 119) were randomized to placebo or resveratrol 500 mg orally once daily (with dose escalation by 500-mg increments every 13 weeks, ending with 1,000 mg twice daily). Brain MRI and CSF collection were performed at baseline and after completion of treatment. Detailed pharmacokinetics were performed on a subset (n = 15) at baseline and weeks 13, 26, 39, and 52. RESULTS: Resveratrol and its major metabolites were measurable in plasma and CSF. The most common adverse events were nausea, diarrhea, and weight loss. CSF Aβ40 and plasma Aβ40 levels declined more in the placebo group than the resveratrol-treated group, resulting in a significant difference at week 52. Brain volume loss was increased by resveratrol treatment compared to placebo. CONCLUSIONS: Resveratrol was safe and well-tolerated. Resveratrol and its major metabolites penetrated the blood–brain barrier to have CNS effects. Further studies are required to interpret the biomarker changes associated with resveratrol treatment. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with AD resveratrol is safe, well-tolerated, and alters some AD biomarker trajectories. The study is rated Class II because more than 2 primary outcomes were designated.
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spelling pubmed-46262442015-11-12 A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease Turner, R. Scott Thomas, Ronald G. Craft, Suzanne van Dyck, Christopher H. Mintzer, Jacobo Reynolds, Brigid A. Brewer, James B. Rissman, Robert A. Raman, Rema Aisen, Paul S. Neurology Article OBJECTIVE: A randomized, placebo-controlled, double-blind, multicenter 52-week phase 2 trial of resveratrol in individuals with mild to moderate Alzheimer disease (AD) examined its safety and tolerability and effects on biomarker (plasma Aβ40 and Aβ42, CSF Aβ40, Aβ42, tau, and phospho-tau 181) and volumetric MRI outcomes (primary outcomes) and clinical outcomes (secondary outcomes). METHODS: Participants (n = 119) were randomized to placebo or resveratrol 500 mg orally once daily (with dose escalation by 500-mg increments every 13 weeks, ending with 1,000 mg twice daily). Brain MRI and CSF collection were performed at baseline and after completion of treatment. Detailed pharmacokinetics were performed on a subset (n = 15) at baseline and weeks 13, 26, 39, and 52. RESULTS: Resveratrol and its major metabolites were measurable in plasma and CSF. The most common adverse events were nausea, diarrhea, and weight loss. CSF Aβ40 and plasma Aβ40 levels declined more in the placebo group than the resveratrol-treated group, resulting in a significant difference at week 52. Brain volume loss was increased by resveratrol treatment compared to placebo. CONCLUSIONS: Resveratrol was safe and well-tolerated. Resveratrol and its major metabolites penetrated the blood–brain barrier to have CNS effects. Further studies are required to interpret the biomarker changes associated with resveratrol treatment. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with AD resveratrol is safe, well-tolerated, and alters some AD biomarker trajectories. The study is rated Class II because more than 2 primary outcomes were designated. Lippincott Williams & Wilkins 2015-10-20 /pmc/articles/PMC4626244/ /pubmed/26362286 http://dx.doi.org/10.1212/WNL.0000000000002035 Text en © 2015 American Academy of Neurology This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.
spellingShingle Article
Turner, R. Scott
Thomas, Ronald G.
Craft, Suzanne
van Dyck, Christopher H.
Mintzer, Jacobo
Reynolds, Brigid A.
Brewer, James B.
Rissman, Robert A.
Raman, Rema
Aisen, Paul S.
A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease
title A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease
title_full A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease
title_fullStr A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease
title_full_unstemmed A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease
title_short A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease
title_sort randomized, double-blind, placebo-controlled trial of resveratrol for alzheimer disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626244/
https://www.ncbi.nlm.nih.gov/pubmed/26362286
http://dx.doi.org/10.1212/WNL.0000000000002035
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