Investigating NeuroinflammaTion UnderlyIng Postoperative Brain Connectivity Changes, POCD, Delirium in Older Adults (INTUIT)

• ClinicalTrials.gov Identifier: NCT03273335
• Recruitment Status: Completed
• First Posted: September 6, 2017
• Last Update Posted: November 16, 2022
• Sponsor: Duke University
• Collaborator: National Institute on Aging (NIA)
• Information provided by (Responsible Party): Duke University

Study Description

Brief Summary:

(From NIH reporter) Each year >16 million older Americans undergo anesthesia and surgery, and up to 40% of these patients develop postoperative cognitive dysfunction (POCD), a syndrome of postoperative thinking and memory deficits. Although distinct from delirium, POCD (like delirium) is associated with decreased quality of life, long term cognitive decline, early retirement, increased mortality, and a possible increased risk for developing dementia such as Alzheimer's disease. Understanding the etiology of POCD will likely help promote strategies to treat and/or prevent it. A dominant theory holds that brain inflammation causes POCD, but little work has directly tested this theory in humans. The preliminary data of this team strongly suggest that there is significant postoperative neuro-inflammation in older adults who develop POCD. In this K76 award, the investigators will prospectively obtain pre- and post-operative cognitive testing, fMRI imaging and CSF samples in 200 surgical patients over age 65. This will allow the investigators to evaluate the role of specific neuro-inflammatory processes in POCD and its underlying brain connectivity changes.

Condition or disease	Intervention/treatment
Delirium	Device: Millipore biomarker assay plate

Detailed Description:

Each year >16 million older Americans undergo anesthesia and surgery, and up to 40% of these patients develop postoperative cognitive dysfunction (POCD), a syndrome of postoperative thinking and memory deficits. Although distinct from delirium, POCD (like delirium) is associated with decreased quality of life, long term cognitive decline, early retirement, increased mortality, and a possible increased risk for developing dementia such as Alzheimer's disease. Understanding the etiology of POCD will likely help promote strategies to treat and/or prevent it. A dominant theory holds that brain inflammation causes POCD, but little work has directly tested this theory in humans. The preliminary data of this team strongly suggest that there is significant postoperative neuro-inflammation in older adults who develop POCD. In this K76 award, the investigators will prospectively obtain pre- and post-operative cognitive testing, fMRI imaging and CSF samples in 200 surgical patients over age 65. This will allow the investigators to evaluate the role of specific neuro-inflammatory processes in POCD and its underlying brain connectivity changes.

Study Design

• Study Type: Observational
• Actual Enrollment: 201 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Investigating NeuroinflammaTion UnderlyIng Postoperative Brain Connectivity Changes, POCD, Delirium in Older Adults
• Actual Study Start Date: June 15, 2017
• Actual Primary Completion Date: November 11, 2021
• Actual Study Completion Date: October 21, 2022

Groups and Cohorts

Group/Cohort	Intervention/treatment
Surgical patients; Surgical patients will undergo CSF biomarker assays, cognitive testing and fMRI scans.	Device: Millipore biomarker assay plate; Millipore biomarker assay plate CSF cytokine assays as well as CSF flow cytometry

Outcome Measures

Primary Outcome Measures :

1. Correlation between Perioperative changes in CSF Monocytes and perioperative changes in cognition (continuous cognitive index change) [ Time Frame: from before to 6 weeks after anesthesia/surgery ]
   as above

Biospecimen Retention:   Samples With DNA

CSF, Blood/Serum

Eligibility Criteria

• Ages Eligible for Study: 60 Years to 130 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Surgical patients age 60 and above, as described above.

Criteria

Inclusion Criteria:

• Age 60 and above
• Having surgery scheduled to last > or = to 2 hours at Duke University Medical Center (ie Duke Hospital, Duke Medicine Pavilion, Duke Regional Hospital, Durham VA, Duke Raleigh Hospital)

Exclusion Criteria:

• Anticoagulants (per ASRA guidelines)
• Current use of chemotherapeutic agents with known cognitive effects.

Contacts and Locations

Locations

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27712

Sponsors and Collaborators

Duke University

National Institute on Aging (NIA)

Investigators

• Principal Investigator: Miles Berger, MD, PhD; Duke University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Berger M, Murdoch DM, Staats JS, Chan C, Thomas JP, Garrigues GE, Browndyke JN, Cooter M, Quinones QJ, Mathew JP, Weinhold KJ; MADCO-PC Study Team. Flow Cytometry Characterization of Cerebrospinal Fluid Monocytes in Patients With Postoperative Cognitive Dysfunction: A Pilot Study. Anesth Analg. 2019 Nov;129(5):e150-e154. doi: 10.1213/ANE.0000000000004179.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT03273335
• Other Study ID Numbers: Pro00083288; 1K76AG057022 ( U.S. NIH Grant/Contract )
• First Posted: September 6, 2017
• Last Update Posted: November 16, 2022
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Delirium; Neuroinflammatory Diseases; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Inflammation; Pathologic Processes