Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2021;81(2):557-568.
doi: 10.3233/JAD-201610.

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

Sid E O'Bryant  1   2 , Fan Zhang  1   3 , Melissa Petersen  1   3 , Leigh Johnson  1   2 , James Hall  1   2 , Robert A Rissman  3   4
Affiliations
Free PMC article
Clinical Trial

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

Sid E O'Bryant et al. J Alzheimers Dis. 2021.
Free PMC article

Abstract

Background: 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, TNFα, 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.

Keywords: Alzheimer’s disease; clinical trial; predictive biomarker; rosiglitazone.

PubMed Disclaimer

Conflict of interest statement

Authors’ disclosures available online (https://www.j-alz.com/manuscript-disclosures/20-1610r1).

Figures

Fig. 1
Fig. 1
Precision medicine approach to trial enrollment with predictive biomarkers.
Fig. 2
Fig. 2
Predictive biomarker accuracy in predicting treatment response in the Phase 2 trial.
Fig. 3
Fig. 3
Predictive biomarker accuracy in identifying responders versus non-responders in the Phase 3 trial AV105640.
Fig. 4
Fig. 4
Predictive biomarker accuracy in identifying responders versus non-responders in the Phase 3 trial AV102672.
Fig. 5
Fig. 5
Predictive biomarker accuracy in identifying responders versus non-responders in the Phase 3 trial AV102670.
Fig. 6
Fig. 6
Predictive biomarker accuracy in identifying responders versus non-responders in across 2mg XR and 8mg XR arms across trials.
Fig. 7
Fig. 7
Predictive accuracy in identifying responders versus non-responders dosages.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Alzheimer’s Association (2020) 2020 Alzheimer’s disease facts and figures. Alzheimers Dement 16, 391–460.
    1. Alzheimer’s Association (2018) 2018 Alzheimer’s disease facts and figures. Alzheimers Dement 14, 367–429.
    1. Hurd MD, Martorell P, Delavande A, Mullen KJ, Langa KM (2013) Monetary costs of dementia in the United States. N Engl J Med 368, 1326–1334. - PMC - PubMed
    1. Precision Medicine, FDA, https://www.fda.gov/medical-devices/vitro-diagnostics/precision-medicine Last updated September 27, 2018, Accessed on March 12, 2021.
    1. Hampel H, O’Bryant SE, Durrleman S, Younesi E, Rojkova K, Escott-Price V, Corvol JC, Broich K, Dubois B, Lista S (2017) A Precision Medicine Initiative for Alzheimer’s disease: The road ahead to biomarker-guided integrative disease modeling. Climacteric 20, 107–118. - PubMed

Publication types

MeSH terms