The MARBLE Study Protocol: Modulating ApoE Signaling to Reduce Brain Inflammation, DeLirium, and PostopErative Cognitive Dysfunction.
Journal Article (Journal Article)
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.
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Duke Authors
- Abi Hachem, Ralph
- Adams Jr., Samuel Bruce
- Amundsen, Cindy Louise
- Anakwenze, Oke Adrian
- Berchuck, Andrew
- Berger, Miles
- Bolognesi, Michael Paul
- Brigman, Brian Eugene
- Browndyke, Jeffrey Nicholas
- Davidson, Brittany A
- Devinney, Michael
- Easley, Mark Erik
- Eleswarpu, Sarada
- Erdmann, Detlev
- Erickson, Melissa Maria
- Gadsden, Jeffrey Charles
- Gingrich, Jeffrey Rae
- Habib, Ashraf Samir
- Hartwig, Matthew
- Havrilesky, Laura Jean
- Heflin, Mitchell Tod
- Hopkins, Thomas Joseph
- Inman, Brant Allen
- Jang, David W
- Kahmke, Russel Roy
- Kawasaki, Amie
- Klapper, Jacob A
- Klifto, Christopher Scott
- Klinger, Rebecca Yasmin
- Knechtle, Stuart Johnston
- Laskowitz, Daniel Todd
- Lee, Walter T
- Lewis, Brian David
- Lidsky, Michael Evan
- Lipkin, Michael Eric
- Mantyh, Christopher Ritchie
- McDonald, Shelley R
- Migaly, John
- Miller, Timothy Ellis
- Mithani, Suhail Kamrudin
- Moretti, Eugene William
- Mosca, Paul Joseph
- Moul, Judd Wendell
- Olson, Steven Arthur
- Peterson, Andrew Charles
- Phillips, Brett Thomas
- Polascik, Thomas James
- Preminger, Glenn Michael
- Previs, Rebecca A
- Robertson, Cary Nobles
- Rockhold, Frank Wesley
- Scales Jr., Charles Douglas
- Scheri, Randall Paul
- Shah, Kevin Naresh
- Siddiqui, Nazema Yusuf
- Southerland, Kevin William
- Stang, Michael Tracey
- Terrando, Niccolò
- Visco, Anthony Gabriele
- Weidner, Alison Catherine
- Woldorff, Marty G.
- Zani Jr., Sabino
Cited Authors
- VanDusen, KW; Eleswarpu, S; Moretti, EW; Devinney, MJ; Crabtree, DM; Laskowitz, DT; Woldorff, MG; Roberts, KC; Whittle, J; Browndyke, JN; Cooter, M; Rockhold, FW; Anakwenze, O; Bolognesi, MP; Easley, ME; Ferrandino, MN; Jiranek, WA; Berger, M; MARBLE Study Investigators,
Published Date
- 2020
Published In
Volume / Issue
- 75 / 4
Start / End Page
- 1319 - 1328
PubMed ID
- 32417770
Pubmed Central ID
- PMC7923142
Electronic International Standard Serial Number (EISSN)
- 1875-8908
Digital Object Identifier (DOI)
- 10.3233/JAD-191185
Language
- eng
Conference Location
- Netherlands