Interventions for Postoperative Delirium: Biomarker-3
- Conditions
- Delirium
- Registration Number
- NCT03124303
- Lead Sponsor
- University of Wisconsin, Madison
- Brief Summary
The IPOD-B3 study aims to characterize the relationship between premorbid brain activity and postoperative delirium in patients undergoing major surgery. This is a expansion of the NeuroVISION Bolt-On study, NCT01980511.
- Detailed Description
9/8/21-- Deleted two Outcome Measures pending IRB approval.
11/5/21-- added outcome measures after IRB approval.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 470
- Cohort 1: Age ≥65 years
- Cohort 2: Age ≥60 years
- Anticipated length of hospital stay of at least 2 days after surgery that occurs under general or neuraxial anesthesia
- Written Informed Consent for potential participation prior to surgery
- Contraindication to EEG
- Unable or unwilling to attend the follow-up appointments
- Documented history of dementia
- Deemed incapable of providing consent by surgical team
- Residing in a nursing home
- Undergoing intracranial surgery
- Unable to complete neurocognitive testing due to language, vision or hearing impairment
- Unable to communicate with the research staff due to language barriers
- For optional MRI portion of the study: Contraindication to MRI (e.g., implanted devices not safe for MRI studies, claustrophobia, unable to lie flat or still)
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Functional Connectivity Pre-operative measure: Up to 4 weeks prior to surgery. Post-operative measure: Post-Operative days 1-4 Change from baseline functional connectivity at immediate postoperative period and association between delirium (CAM) and functional connectivity of the cingulate cortex
Brain state change Post-operative day 1 through 4 Quantified by the MSD across regions of interest from resting state time-series to randomly spaced points across the time-series. Measured for Cohort 2 only.
- Secondary Outcome Measures
Name Time Method Connectivity during delirium Post-operative day 1 through 4 Dynamic causal modeling of cortical connectivity during delirium.
Inflammation Pre-operative measure: Up to 4 weeks prior to surgery. Post-operative measure: POD1-4 Assess the changes from preoperative to postoperative EEG associated with delirium and change in plasma/cerebrospinal fluid (CSF) IL-6 or other biomarkers (e.g. other cytokines or markers of neronal injury)
Biomarkers Post-operative day 1 through 4 Identify biomarkers of delirium and neural damage through changes in circulating plasma proteins and molecules (through mass spectometry)
Brain measurements Preoperative MRI will occur up to 4-weeks prior to surgery. Delirium is followed postoperatively, days 1-4 Assess the association between preoperative white matter connectivity (DTI) and cortical thickness (derived from MRI) and postoperative delirium
Long term cognition Pre-operative cognition measures will occur up to 4 weeks prior to surgery. Long term post-operative cognition measured 2 years after surgery. Identify predictors of delirium severity and incidence, for change in cognition from preoperatively to two-years postoperatively.
Baseline cognition, specific and global. Cognition is assessed preoperatively. Participants are followed for delirium on postoperative days 1-4 Examine the association between preoperative cognition using a neuropsychological battery, and postoperative delirium incidence.
Biomarkers and brain measurements Pre-op measures: up to 4 weeks prior to surgery. Post-op measures: one year, and two years, after surgery. Assess the changes in cognition and biomarkers over one year with EEG changes.
Representativeness of surgical population Pre-op MRI: up to 4 weeks prior to surgery. Identify whether patients who consent to the MRI are reflective of the surgical population.
Genetics and delirium Pre-op blood collected up to 4 weeks prior to surgery. Post-operative delirium measured on postoperative days 1-4. Post-operative blood collected on postoperative days 1-4. Long term blood collected 90 days and 1 year after surgery. Identify genetic and epigenetic changes associated with delirium and its pathogenesis.
Postoperative amyloid beta deposition and delirium Post-operative delirium measured on postoperative days 1-4. PET imaging will occur 90 days after surgery. Identify associations between delirium and amyloid beta deposition detected by Positron Emission Tomography at 90 days after surgery in sub-study IPOD-PET.
Long term changes in amyloid beta deposition and delirium Pre-operative PET imaging will occur up to 4 weeks prior to surgery. Post-operative delirium measured on postoperative days 1-4. Post-operative PET imaging will occur 1 year after surgery. Identify associations between delirium and amyloid beta deposition detected by Positron Emission Tomography preoperatively and 1 year after surgery in sub-study IPOD-PET2.
Mismatch negativity Post-operative day 1 through 4 EEG mismatch negativity during delirium compared to resolution of delirium.
Resolution of slow wave activity Post-operative day 1 through 4 Slow wave activity during delirium compared to resolution of delirium.
Effects of inflammation on brain activity Post-operative day 1 through 4 EEG correlations with biomarkers of inflammation and neuronal injury.
Delirium subtypes - neuronal dynamics Post-operative day 1 through 4 EEG neuronal dynamics (energy landscape analysis) during hyperactive vs hypoactive delirium.
Delirium subtypes - predisposing neuronal dynamics Up to 4 weeks prior to surgery. Preoperative neuronal dynamics between hyperactive and hypoactive delirium.
Delirium subtypes - network stitching Post-operative day 1 through 4 Task evoked network switching and locus coeruleus activity between hyperactive and hypoactive delirium.
Delirium subtypes - network integration Up to 4 weeks prior to surgery. Preoperative brain network integration vs differentiation between hyperactive and hypoactive delirium.
Pupillary responses Post-operative day 1 through 4 Pupillary response during rest and cognitive task in delirious versus nondelirious participants.
Metabolism and SWA Post-operative day 1 through 4 Correlation between SWA location, delirium subtype, and MCT2 expression.
Injury versus inflammation 4 weeks prior to surgery to 1 year post-surgery Delayed resolution of biomarkers of neuronal dysfunction and inflammation as competing theories to neuronal injury.
Neuronal injury - surgery type Post-operative day 1 through 4 Association between biomarkers of neuronal injury and type of surgery.
Change in cognition Post-operative day 1 through 4 Association of biomarkers of neuronal injury with change in cognition.
Trial Locations
- Locations (1)
University of Wisconsin-Madison
🇺🇸Madison, Wisconsin, United States