The MARBLE Study Protocol: Modulating ApoE Signaling to Reduce Brain Inflammation, DeLirium, and PostopErative Cognitive Dysfunction.
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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.
SubjectMARBLE Study Investigators
Published Version (Please cite this version)10.3233/jad-191185
Publication InfoVanDusen, Keith W; Eleswarpu, Sarada; Moretti, Eugene W; Devinney, Michael J; Crabtree, Donna M; Laskowitz, Daniel T; ... MARBLE Study Investigators (2020). The MARBLE Study Protocol: Modulating ApoE Signaling to Reduce Brain Inflammation, DeLirium, and PostopErative Cognitive Dysfunction. Journal of Alzheimer's disease : JAD, 75(4). pp. 1319-1328. 10.3233/jad-191185. Retrieved from https://hdl.handle.net/10161/21265.
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Associate Professor of Orthopaedic Surgery
Complex shoulder and elbow surgeon, researcher and innovator.
Associate Professor of Anesthesiology
My research team focuses on understanding the cause of postoperative cognitive dysfunction (POCD) and delirium, and whether these disorders are caused by perioperative changes in Alzheimer's disease pathways. We are also interested in whether delirium or POCD are associated with an increased long term risk of developing Alzheimer's disease. Towards these ends, we use a combination of methods including cognitive testing, CSF and blood sampling, functional neuroimaging, and rigorous biochemical as
Associate Professor of Psychiatry and Behavioral Sciences
Dr. Browndyke is an Associate Professor of Geriatric Behavioral Health in the Department of Psychiatry & Behavioral Sciences. He also holds affiliate faculty appointments with the Duke Brain Imaging & Analysis Center (BIAC), Duke Institute for Brain Science (DIBS), Center for Cognitive Neuroscience (CCN), and the Duke Center for Geriatric Surgery. He has dual appointment to the Duke University Medical Center and the Durham VA Medical Center, the latter of which is where his c
Associate Professor of Orthopaedic Surgery
Associate Professor of Surgery
Professor of Neurology
Our laboratory uses molecular biology, cell culture, and animal modeling techniques to examine the CNS response to acute injury. In particular, our laboratory examines the role of microglial activation and the endogenous CNS inflammatory response in exacerbating secondary injury following acute brain insult. Much of the in vitro work in this laboratory is dedicated to elucidating cellular responses to injury with the ultimate goal of exploring new therapeutic interventions in the clinical settin
Professor of Biostatistics & Bioinformatics
Frank is a fulltime Professor of Biostatistics and Bioinformatics at Duke University Medical Center (Scholars at Duke), Affiliate Professor of Biostatistics at Virginia Commonwealth University, and Managing Partner of HunterRockhold, Inc. His 40+-year career includes senior research positions at Lilly, Merck, and GlaxoSmithKline, where he retired as Chief Safety Officer and Senior Vice President of Global Clini
Assistant Professor of Anesthesiology
I am a UK trained Anesthesiologist with special interests in Critical Care and Perioperative Medicine. I aim to combine my clinical practice with my research interests to reduce the risks associated with Major Surgery for all patients, but especially those at highest risk of complications.My research interests are in preoperative optimization, including exercise and nutritional prehabilitation, as well as investigating how subclinical autonomic dysfunction impacts on key outcom
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