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NCT Number: NCT03124303

Interventions for Postoperative Delirium: Biomarker-3

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.

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Key information

Conditions

Delirium Confusion Mental Disorders Nervous System Diseases Neurobehavioral Manifestations Neurocognitive Disorders Neurologic Manifestations Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

60 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

High Density-Electroencephalogram

Procedure

EEG is a safe non-invasive technology without complications that may be used to help diagnose delirium

Other names: EEG

Magnetic Resonance Imaging

Procedure

MRI scan of brain

Other names: MRI

Blood specimen collection

Procedure

Blood will be collected from participants

Pupillometry

Diagnostic Test

A pupillometer is a device that measures the size of the pupils.

Primary outcomes

  1. 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

  2. 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.

Secondary outcomes

  1. 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)

  2. 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)

  3. 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

  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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Mismatch negativity

    Time frame: Post-operative day 1 through 4

    EEG mismatch negativity during delirium compared to resolution of delirium.

  14. Resolution of slow wave activity

    Time frame: Post-operative day 1 through 4

    Slow wave activity during delirium compared to resolution of delirium.

  15. Connectivity during delirium

    Time frame: Post-operative day 1 through 4

    Dynamic causal modeling of cortical connectivity during delirium.

  16. Effects of inflammation on brain activity

    Time frame: Post-operative day 1 through 4

    EEG correlations with biomarkers of inflammation and neuronal injury.

  17. Delirium subtypes - neuronal dynamics

    Time frame: Post-operative day 1 through 4

    EEG neuronal dynamics (energy landscape analysis) during hyperactive vs hypoactive delirium.

  18. Delirium subtypes - predisposing neuronal dynamics

    Time frame: Up to 4 weeks prior to surgery.

    Preoperative neuronal dynamics between hyperactive and hypoactive delirium.

  19. 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.

  20. Delirium subtypes - network integration

    Time frame: Up to 4 weeks prior to surgery.

    Preoperative brain network integration vs differentiation between hyperactive and hypoactive delirium.

  21. Pupillary responses

    Time frame: Post-operative day 1 through 4

    Pupillary response during rest and cognitive task in delirious versus nondelirious participants.

  22. Metabolism and SWA

    Time frame: Post-operative day 1 through 4

    Correlation between SWA location, delirium subtype, and MCT2 expression.

  23. 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.

  24. Neuronal injury - surgery type

    Time frame: Post-operative day 1 through 4

    Association between biomarkers of neuronal injury and type of surgery.

  25. Change in cognition

    Time frame: Baseline to 1 year post-surgery

    Association of biomarkers of neuronal injury with change in cognition at 1 year.

  26. Change in cognition

    Time frame: Post-operative day 1 through 4

    Association of biomarkers of neuronal injury with change in cognition.

Study contacts

Contact information is provided by the study sponsor or research team.

David Kunkel, BS

CONTACT

[email protected]

608-262-6469

Frankie Ingram, BS

CONTACT

[email protected]

608-262-6469

Sponsors and collaborators

Lead sponsor

University of Wisconsin, Madison

Other

Collaborators

  • National Institute on Aging (NIA)

Registry information

Acronym: IPOD-B3

Important dates

Study start
2017
Primary completion
2029
Study completion
2029
First posted
Apr 21, 2017
Registry last updated
Dec 15, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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