Interventions for Postoperative Delirium: Biomarker-3 (IPOD-B3)

December 10, 2025 updated by: University of Wisconsin, Madison
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

9/8/21-- Deleted two Outcome Measures pending IRB approval.

11/5/21-- added outcome measures after IRB approval.

Study Type

Observational

Enrollment (Estimated)

468

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • Recruiting
        • University of Wisconsin-Madison
        • Contact:
        • Contact:
        • Principal Investigator:
          • Robert Pearce, MD PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

65 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Cohort 1: Patients, 65 years of age and older, undergoing surgery with an estimated length of stay of 2 days or greater.

Cohort 2: Patients, 60 years of age and older, undergoing surgery with an estimated length of stay of 2 days or greater.

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Participants 1-320
First 320 participants enrolled
Procedure: High Density-Electroencephalogram
EEG is a safe non-invasive technology without complications that may be used to help diagnose delirium
Other Names:
  • EEG
Procedure: Magnetic Resonance Imaging
MRI scan of brain
Other Names:
  • MRI
Participants 321-470
Final 150 participants enrolled
Procedure: High Density-Electroencephalogram
EEG is a safe non-invasive technology without complications that may be used to help diagnose delirium
Other Names:
  • EEG
Procedure: Magnetic Resonance Imaging
MRI scan of brain
Other Names:
  • MRI
Procedure: Blood specimen collection
Blood will be collected from participants
Diagnostic test: Pupillometry
A pupillometer is a device that measures the size of the pupils.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Functional Connectivity
Time Frame: 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
Pre-operative measure: Up to 4 weeks prior to surgery. Post-operative measure: Post-Operative days 1-4
Brain state change
Time Frame: 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.
Post-operative day 1 through 4

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Inflammation
Time Frame: 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)
Pre-operative measure: Up to 4 weeks prior to surgery. Post-operative measure: POD1-4
Biomarkers
Time Frame: Post-operative day 1 through 4
Identify biomarkers of delirium and neural damage through changes in circulating plasma proteins and molecules (through mass spectometry)
Post-operative day 1 through 4
Brain measurements
Time Frame: 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
Preoperative MRI will occur up to 4-weeks prior to surgery. Delirium is followed postoperatively, days 1-4
Long term cognition
Time Frame: Pre-operative cognition measures will occur up to 4 weeks prior to surgery. Post-operative delirium measured on postoperative days 1-4. Long term post-operative cognition measured 1 year after surgery.
Examine the incidence of delirium with change in cognition from preoperatively to one-year postoperatively.
Pre-operative cognition measures will occur up to 4 weeks prior to surgery. Post-operative delirium measured on postoperative days 1-4. Long term post-operative cognition measured 1 year after surgery.
Long term cognition
Time Frame: Pre-operative measure: Up to 4 weeks prior to surgery. Post-operative measure: Up to two years after surgery
Assess the impact of delirium, preoperative and postoperative imaging biomarkers with a change in long term cognition
Pre-operative measure: Up to 4 weeks prior to surgery. Post-operative measure: Up to two years after surgery
Baseline cognition, specific and global.
Time Frame: 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.
Cognition is assessed preoperatively. Participants are followed for delirium on postoperative days 1-4
Biomarkers and brain measurements
Time Frame: 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.
Pre-op measures: up to 4 weeks prior to surgery. Post-op measures: one year, and two years, after surgery.
Representativeness of surgical population
Time Frame: Pre-op MRI: up to 4 weeks prior to surgery.
Identify whether patients who consent to the MRI are reflective of the surgical population.
Pre-op MRI: up to 4 weeks prior to surgery.
Genetics and delirium
Time Frame: 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.
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.
Postoperative amyloid beta deposition and delirium
Time Frame: 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.
Post-operative delirium measured on postoperative days 1-4. PET imaging will occur 90 days after surgery.
Long term changes in amyloid beta deposition and delirium
Time Frame: 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.
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.
Long term cognition
Time Frame: 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.
Pre-operative cognition measures will occur up to 4 weeks prior to surgery. Long term post-operative cognition measured 2 years after surgery.
Mismatch negativity
Time Frame: Post-operative day 1 through 4
EEG mismatch negativity during delirium compared to resolution of delirium.
Post-operative day 1 through 4
Resolution of slow wave activity
Time Frame: Post-operative day 1 through 4
Slow wave activity during delirium compared to resolution of delirium.
Post-operative day 1 through 4
Connectivity during delirium
Time Frame: Post-operative day 1 through 4
Dynamic causal modeling of cortical connectivity during delirium.
Post-operative day 1 through 4
Effects of inflammation on brain activity
Time Frame: Post-operative day 1 through 4
EEG correlations with biomarkers of inflammation and neuronal injury.
Post-operative day 1 through 4
Delirium subtypes - neuronal dynamics
Time Frame: Post-operative day 1 through 4
EEG neuronal dynamics (energy landscape analysis) during hyperactive vs hypoactive delirium.
Post-operative day 1 through 4
Delirium subtypes - predisposing neuronal dynamics
Time Frame: Up to 4 weeks prior to surgery.
Preoperative neuronal dynamics between hyperactive and hypoactive delirium.
Up to 4 weeks prior to surgery.
Delirium subtypes - network stitching
Time Frame: Post-operative day 1 through 4
Task evoked network switching and locus coeruleus activity between hyperactive and hypoactive delirium.
Post-operative day 1 through 4
Delirium subtypes - network integration
Time Frame: Up to 4 weeks prior to surgery.
Preoperative brain network integration vs differentiation between hyperactive and hypoactive delirium.
Up to 4 weeks prior to surgery.
Pupillary responses
Time Frame: Post-operative day 1 through 4
Pupillary response during rest and cognitive task in delirious versus nondelirious participants.
Post-operative day 1 through 4
Metabolism and SWA
Time Frame: Post-operative day 1 through 4
Correlation between SWA location, delirium subtype, and MCT2 expression.
Post-operative day 1 through 4
Injury versus inflammation
Time Frame: 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.
4 weeks prior to surgery to 1 year post-surgery
Neuronal injury - surgery type
Time Frame: Post-operative day 1 through 4
Association between biomarkers of neuronal injury and type of surgery.
Post-operative day 1 through 4
Change in cognition
Time Frame: Baseline to 1 year post-surgery
Association of biomarkers of neuronal injury with change in cognition at 1 year.
Baseline to 1 year post-surgery
Change in cognition
Time Frame: Post-operative day 1 through 4
Association of biomarkers of neuronal injury with change in cognition.
Post-operative day 1 through 4

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Wisconsin, Madison

Collaborators

National Institute on Aging (NIA)

Investigators

  • Principal Investigator: Robert Pearce, MD, PhD, University of Wisconsin, Madison

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 13, 2017

Primary Completion (Estimated)

December 1, 2029

Study Completion (Estimated)

December 1, 2029

Study Registration Dates

First Submitted

March 29, 2017

First Submitted That Met QC Criteria

April 18, 2017

First Posted (Actual)

April 21, 2017

Study Record Updates

Last Update Posted (Estimated)

December 15, 2025

Last Update Submitted That Met QC Criteria

December 10, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2015-0374
  • A530900 (Other Identifier: UW Madison)
  • SMPH\ANESTHESIOLOGY (Other Identifier: UW Madison)
  • 1K23AG055700-01A1 (U.S. NIH Grant/Contract)
  • 1R01AG063849-01 (U.S. NIH Grant/Contract)
  • Protocol Version 1/15/25 (Other Identifier: UW Madison)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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