Skip to main content

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

Publication ,  Journal Article
VanDusen, KW; Eleswarpu, S; Moretti, EW; Devinney, MJ; Crabtree, DM; Laskowitz, DT; Woldorff, MG; Roberts, KC; Whittle, J; Browndyke, JN ...
Published in: J Alzheimers Dis

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.

Duke Scholars

Sandhya Anand Lagoo-Deenadayalan
Author Sandhya Anand Lagoo-Deenadayalan Surgery, Minimally Invasive Surgery
Sarada Eleswarpu
Author Sarada Eleswarpu Anesthesiology, General, Vascular, High Risk Transplant & Cr ...
Eugene William Moretti
Author Eugene William Moretti Anesthesiology, General, Vascular, High Risk Transplant & Cr ...
Michael Devinney
Author Michael Devinney Anesthesiology, Critical Care Medicine
Daniel Todd Laskowitz
Author Daniel Todd Laskowitz Neurology, Neurocritical Care
Marty G. Woldorff
Author Marty G. Woldorff Psychiatry & Behavioral Sciences, Behavioral Medicine & Neur ...
Jeffrey Nicholas Browndyke
Author Jeffrey Nicholas Browndyke Psychiatry & Behavioral Sciences, Behavioral Medicine & Neur ...
Frank Wesley Rockhold
Author Frank Wesley Rockhold Biostatistics & Bioinformatics, Division of Biostatistics
Oke Adrian Anakwenze
Author Oke Adrian Anakwenze Orthopaedic Surgery
Michael Paul Bolognesi
Author Michael Paul Bolognesi Orthopaedic Surgery
Mark Erik Easley
Author Mark Erik Easley Orthopaedic Surgery
Miles Berger
Author Miles Berger Anesthesiology, Neuroanesthesia
Samuel Bruce Adams Jr.
Author Samuel Bruce Adams Jr. Orthopaedic Surgery
Cindy Louise Amundsen
Author Cindy Louise Amundsen Obstetrics and Gynecology, Urogynecology
Andrew Berchuck
Author Andrew Berchuck Obstetrics and Gynecology, Gynecologic Oncology
Brian Eugene Brigman
Author Brian Eugene Brigman Orthopaedic Surgery
Brittany A Davidson
Author Brittany A Davidson Obstetrics and Gynecology, Gynecologic Oncology
Detlev Erdmann
Author Detlev Erdmann Surgery, Plastic, Maxillofacial, and Oral Surgery
Melissa Maria Erickson
Author Melissa Maria Erickson Orthopaedic Surgery
Jeffrey Charles Gadsden
Author Jeffrey Charles Gadsden Anesthesiology, Regional
Jeffrey Rae Gingrich
Author Jeffrey Rae Gingrich Urology
Ashraf Samir Habib
Author Ashraf Samir Habib Anesthesiology, Women's
Ralph Abi Hachem
Author Ralph Abi Hachem Rhinology and Skull Base Surgery
Matthew Hartwig
Author Matthew Hartwig Surgery, Cardiovascular and Thoracic Surgery
Laura Jean Havrilesky
Author Laura Jean Havrilesky Obstetrics and Gynecology, Gynecologic Oncology
Mitchell Tod Heflin
Author Mitchell Tod Heflin Medicine, Geriatrics
David W Jang
Author David W Jang Rhinology and Skull Base Surgery
Russel Roy Kahmke
Author Russel Roy Kahmke Head & Neck Surgical Oncology
Amie Kawasaki
Author Amie Kawasaki Obstetrics and Gynecology, Urogynecology
Jacob A Klapper
Author Jacob A Klapper Surgery, Cardiovascular and Thoracic Surgery