Clinical trial NCT03124303: Interventions for Postoperative Delirium: Biomarker-3
Official title: Interventions for Postoperative Delirium: Biomarker-3
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Delirium
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2017-04-21
Enrollment: 470
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Functional Connectivity
timeFrame: Pre-operative measure: Up to 4 weeks prior to surgery. Post-operative measure: Post-Operative days 1-4
measure: Brain state change
timeFrame: Post-operative day 1 through 4
Secondary outcomes:
measure: Inflammation
timeFrame: Pre-operative measure: Up to 4 weeks prior to surgery. Post-operative measure: POD1-4
measure: Biomarkers
timeFrame: Post-operative day 1 through 4
measure: Brain measurements
timeFrame: Preoperative MRI will occur up to 4-weeks prior to surgery. Delirium is followed postoperatively, days 1-4
measure: Long term cognition
timeFrame: 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.
measure: Long term cognition
timeFrame: Pre-operative measure: Up to 4 weeks prior to surgery. Post-operative measure: Up to two years after surgery
measure: Baseline cognition, specific and global.
timeFrame: Cognition is assessed preoperatively. Participants are followed for delirium on postoperative days 1-4
measure: Biomarkers and brain measurements
timeFrame: Pre-op measures: up to 4 weeks prior to surgery. Post-op measures: one year, and two years, after surgery.
measure: Representativeness of surgical population
timeFrame: Pre-op MRI: up to 4 weeks prior to surgery.
measure: Genetics and delirium
timeFrame: 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.
measure: Postoperative amyloid beta deposition and delirium
timeFrame: Post-operative delirium measured on postoperative days 1-4. PET imaging will occur 90 days after surgery.
measure: Long term changes in amyloid beta deposition and delirium
timeFrame: 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.
measure: Long term cognition
timeFrame: Pre-operative cognition measures will occur up to 4 weeks prior to surgery. Long term post-operative cognition measured 2 years after surgery.
measure: Mismatch negativity
timeFrame: Post-operative day 1 through 4
measure: Resolution of slow wave activity
timeFrame: Post-operative day 1 through 4
measure: Connectivity during delirium
timeFrame: Post-operative day 1 through 4
measure: Effects of inflammation on brain activity
timeFrame: Post-operative day 1 through 4
measure: Delirium subtypes - neuronal dynamics
timeFrame: Post-operative day 1 through 4
measure: Delirium subtypes - predisposing neuronal dynamics
timeFrame: Up to 4 weeks prior to surgery.
measure: Delirium subtypes - network stitching
timeFrame: Post-operative day 1 through 4
measure: Delirium subtypes - network integration
timeFrame: Up to 4 weeks prior to surgery.
measure: Pupillary responses
timeFrame: Post-operative day 1 through 4
measure: Metabolism and SWA
timeFrame: Post-operative day 1 through 4
measure: Injury versus inflammation
timeFrame: 4 weeks prior to surgery to 1 year post-surgery
measure: Neuronal injury - surgery type
timeFrame: Post-operative day 1 through 4
measure: Change in cognition
timeFrame: Baseline to 1 year post-surgery
measure: Change in cognition
timeFrame: Post-operative day 1 through 4
Other outcomes:
Locations:
city: Madison
country: United States
facility: University of Wisconsin-Madison
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Robert Pearce, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Taylor J, Payne T, Casey C, Kunkel D, Parker M, Rivera C, Zetterberg H, Blennow K, Pearce RA, Lennertz RC, McCulloch T, Gaskell A, Sanders RD. Sevoflurane dose and postoperative delirium: a prospective cohort analysis. Br J Anaesth. 2023 Feb;130(2):e289-e297. doi: 10.1016/j.bja.2022.08.022. Epub 2022 Oct 1.
citation: Taylor J, Parker M, Casey CP, Tanabe S, Kunkel D, Rivera C, Zetterberg H, Blennow K, Pearce RA, Lennertz RC, Sanders RD. Postoperative delirium and changes in the blood-brain barrier, neuroinflammation, and cerebrospinal fluid lactate: a prospective cohort study. Br J Anaesth. 2022 Aug;129(2):219-230. doi: 10.1016/j.bja.2022.01.005. Epub 2022 Feb 8.
citation: Tanabe S, Parker M, Lennertz R, Pearce RA, Banks MI, Sanders RD. Reduced Electroencephalogram Complexity in Postoperative Delirium. J Gerontol A Biol Sci Med Sci. 2022 Mar 3;77(3):502-506. doi: 10.1093/gerona/glab352.
citation: White MF, Tanabe S, Casey C, Parker M, Bo A, Kunkel D, Nair V, Pearce RA, Lennertz R, Prabhakaran V, Lindroth H, Sanders RD. Relationships between preoperative cortical thickness, postoperative electroencephalogram slowing, and postoperative delirium. Br J Anaesth. 2021 Aug;127(2):236-244. doi: 10.1016/j.bja.2021.02.028. Epub 2021 Apr 15.
citation: Ballweg T, White M, Parker M, Casey C, Bo A, Farahbakhsh Z, Kayser A, Blair A, Lindroth H, Pearce RA, Blennow K, Zetterberg H, Lennertz R, Sanders RD. Association between plasma tau and postoperative delirium incidence and severity: a prospective observational study. Br J Anaesth. 2021 Feb;126(2):458-466. doi: 10.1016/j.bja.2020.08.061. Epub 2020 Nov 20.
citation: Tanabe S, Mohanty R, Lindroth H, Casey C, Ballweg T, Farahbakhsh Z, Krause B, Prabhakaran V, Banks MI, Sanders RD. Cohort study into the neural correlates of postoperative delirium: the role of connectivity and slow-wave activity. Br J Anaesth. 2020 Jul;125(1):55-66. doi: 10.1016/j.bja.2020.02.027. Epub 2020 Jun 1.