Dataset Information

The MARBLE Study Protocol: Modulating ApoE Signaling to Reduce Brain Inflammation, DeLirium, and PostopErative Cognitive Dysfunction.

ABSTRACT:

Background

Perioperative neurocognitive disorders (PND) are common complications in older adults associated with increased 1-year mortality and long-term cognitive decline. One risk factor for worsened long-term postoperative cognitive trajectory is the Alzheimer's disease (AD) genetic risk factor APOE4. APOE4 is thought to elevate AD risk partly by increasing neuroinflammation, which is also a theorized mechanism for PND. Yet, it is unclear whether modulating apoE4 protein signaling in older surgical patients would reduce PND risk or severity.

Objective

MARBLE is a randomized, blinded, placebo-controlled phase II sequential dose escalation trial designed to evaluate perioperative administration of an apoE mimetic peptide drug, CN-105, in older adults (age?60 years). The primary aim is evaluating the safety of CN-105 administration, as measured by adverse event rates in CN-105 versus placebo-treated patients. Secondary aims include assessing perioperative CN-105 administration feasibility and its efficacy for reducing postoperative neuroinflammation and PND severity.

Methods

201 patients undergoing non-cardiac, non-neurological surgery will be randomized to control or CN-105 treatment groups and receive placebo or drug before and every six hours after surgery, for up to three days after surgery. Chart reviews, pre- and postoperative cognitive testing, delirium screening, and blood and CSF analyses will be performed to examine effects of CN-105 on perioperative adverse event rates, cognition, and neuroinflammation. Trial results will be disseminated by presentations at conferences and peer-reviewed publications.

Conclusion

MARBLE is a transdisciplinary study designed to measure CN-105 safety and efficacy for preventing PND in older adults and to provide insight into the pathogenesis of these geriatric syndromes.

SUBMITTER: VanDusen KW

PROVIDER: S-EPMC7923142 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The MARBLE Study Protocol: Modulating ApoE Signaling to Reduce Brain Inflammation, DeLirium, and PostopErative Cognitive Dysfunction.

VanDusen Keith W KW Eleswarpu Sarada S Moretti Eugene W EW Devinney Michael J MJ Crabtree Donna M DM Laskowitz Daniel T DT Woldorff Marty G MG Roberts Kenneth C KC Whittle John J Browndyke Jeffrey N JN Cooter Mary M Rockhold Frank W FW Anakwenze Oke O Bolognesi Michael P MP Easley Mark E ME Ferrandino Michael N MN Jiranek William A WA Berger Miles M

Journal of Alzheimer's disease : JAD 20200101 4

<h4>Background</h4>Perioperative neurocognitive disorders (PND) are common complications in older adults associated with increased 1-year mortality and long-term cognitive decline. One risk factor for worsened long-term postoperative cognitive trajectory is the Alzheimer's disease (AD) genetic risk factor APOE4. APOE4 is thought to elevate AD risk partly by increasing neuroinflammation, which is also a theorized mechanism for PND. Yet, it is unclear whether modulating apoE4 protein signaling in ...[more]

PMID: 32417770

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Dataset Information

The MARBLE Study Protocol: Modulating ApoE Signaling to Reduce Brain Inflammation, DeLirium, and PostopErative Cognitive Dysfunction.

Background

Objective

Methods

Conclusion

Publications

The MARBLE Study Protocol: Modulating ApoE Signaling to Reduce Brain Inflammation, DeLirium, and PostopErative Cognitive Dysfunction.

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