A Precision Medicine Approach to Treating Alzheimer's Disease Using Rosiglitazone Therapy: A Biomarker Analysis of the REFLECT Trials

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dc.creatorO'Bryant, Sid E.
dc.creatorZhang, Fan
dc.creatorPetersen, Melissa E.
dc.creatorJohnson, Leigh A.
dc.creatorHall, James R.
dc.creatorRissman, Robert A.
dc.creator.orcid0000-0003-0582-5266 (O'Bryant, Sid E.)
dc.creator.orcid0000-0001-7769-8417 (Johnson, Leigh A.)
dc.creator.orcid0000-0002-3920-5877 (Petersen, Melissa E.)
dc.date.accessioned2022-07-07T13:54:27Z
dc.date.available2022-07-07T13:54:27Z
dc.date.issued2021-05-18
dc.description.abstractBackground: The REFLECT trials were conducted to examine the treatment of mild-to-moderate Alzheimer's disease utilizing a peroxisome proliferator-activated receptor gamma agonist. Objective: To generate a predictive biomarker indicative of positive treatment response using samples from the previously conducted REFLECT trials. Methods: Data were analyzed on 360 participants spanning multiple negative REFLECT trials, which included treatment with rosiglitazone and rosiglitazone XR. Support vector machine analyses were conducted to generate a predictive biomarker profile. Results: A pre-defined 6-protein predictive biomarker (IL6, IL10, CRP, TNFɑ, FABP-3, and PPY) correctly classified treatment response with 100% accuracy across study arms for REFLECT Phase II trial (AVA100193) and multiple Phase III trials (AVA105640, AV102672, and AVA102670). When the data was combined across all rosiglitazone trial arms, a global RSG-predictive biomarker with the same 6-protein predictive biomarker was able to accurately classify 98%of treatment responders. Conclusion: A predictive biomarker comprising of metabolic and inflammatory markers was highly accurate in identifying those patients most likely to experience positive treatment response across the REFLECT trials. This study provides additional proof-of-concept that a predictive biomarker can be utilized to help with screening and predicting treatment response, which holds tremendous benefit for clinical trials.
dc.description.sponsorshipResearch reported here was supported by the National Institute on Aging of the National Institutes of Health under Award Numbers R01AG018440, P30AG062429, R01AG051848. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
dc.identifier.citationO'Bryant, S. E., Zhang, F., Petersen, M., Johnson, L., Hall, J., & Rissman, R. A. (2021). A Precision Medicine Approach to Treating Alzheimer's Disease Using Rosiglitazone Therapy: A Biomarker Analysis of the REFLECT Trials. Journal of Alzheimer's disease : JAD, 81(2), 557-568. https://doi.org/10.3233/JAD-201610
dc.identifier.issn1875-8908
dc.identifier.issue2
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31539
dc.identifier.volume81
dc.publisherIOS Press
dc.relation.urihttps://doi.org/10.3233/JAD-201610
dc.rights.holderCopyright © 2021 © The authors. Published by IOS Press
dc.rights.licenseAttribution-NonCommercial 4.0 International (CC BY-NC 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.sourceJournal of Alzheimer's Disease
dc.subjectAlzheimer's disease
dc.subjectclinical trial
dc.subjectpredictive biomarker
dc.subject.meshAlzheimer Disease
dc.subject.meshHumans
dc.subject.meshPPAR gamma
dc.subject.meshPrecision Medicine
dc.subject.meshRosiglitazone
dc.subject.meshThiazolidinediones
dc.titleA Precision Medicine Approach to Treating Alzheimer's Disease Using Rosiglitazone Therapy: A Biomarker Analysis of the REFLECT Trials
dc.typeArticle
dc.type.materialtext

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