The MARBLE Study Protocol: Modulating ApoE Signaling to Reduce Brain Inflammation, DeLirium, and PostopErative Cognitive Dysfunction
| Autor: | Mark E. Easley, Marty G. Woldorff, John Whittle, Frank W. Rockhold, Oke A. Anakwenze, Jeffrey N. Browndyke, Daniel T. Laskowitz, Miles Berger, Keith W. VanDusen, Sarada S Eleswarpu, Michael J. Devinney, Michael P. Bolognesi, Donna M. Crabtree, William A. Jiranek, Mary Cooter, Marble Study Investigators, Kenneth C. Roberts, Eugene W. Moretti, Michael N. Ferrandino |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Placebo Article 03 medical and health sciences 0302 clinical medicine Apolipoproteins E Postoperative Cognitive Complications Biomimetic Materials Internal medicine Medicine Humans Cognitive decline Risk factor Adverse effect business.industry General Neuroscience Anti-Inflammatory Agents Non-Steroidal Delirium General Medicine Perioperative medicine.disease Psychiatry and Mental health Clinical Psychology 030104 developmental biology Neuroprotective Agents Treatment Outcome Encephalitis Geriatrics and Gerontology medicine.symptom business Neurocognitive Postoperative cognitive dysfunction 030217 neurology & neurosurgery |
| Zdroj: | J Alzheimers Dis |
| ISSN: | 1875-8908 |
| Popis: | 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. OBJECTIVES: 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 (AE) 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 drug or placebo 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 neuro-inflammation. 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. |
| Databáze: | OpenAIRE |
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