Recruiting

Observational Study

Sponsor:

University of Tennessee Graduate School of Medicine

Code:

NCT05378659

Conditions

Post-Operative Confusion

Neuroinflammatory Response

Alzheimer Disease

Eligibility Criteria

Sex: All

Age: 60+

Healthy Volunteers: Accepted

Interventions

Montreal Cognitive Assessment

Stroop Test

4AT Delirium

Grooved Pegboard

NACC Cognitive Battery

Study Details

Brief summary:

The purpose of this project is to investigate the role of both neural inflammation and pre-existing neurodegenerative pathology in the risk and pathogenesis of post-operative cognitive dysfunction (POCD). To achieve this goal, the investigators will combine blood and cerebrospinal fluid (CSF) sampling, standardized cognitive tests, and dynamic neurophysiological markers of cortical network dysfunction in the form of event-related potentials (ERPs), to assess the link between neurodegeneration and neuroinflammation in the pathogenesis of POCD.

Conditions

Post-Operative Confusion

Neuroinflammatory Response

Alzheimer Disease

Study ID

NCT05378659

Start date

Nov 1, 2021

Status verified date

May, 2022

Completion date

Sep 30, 2022

Anticipated

Primary completion date

Jun 30, 2022

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 60+

Healthy Volunteers: Accepted

Inclusion Criteria:

  • Males and females 60 years or older in age
  • Subjects scheduled to undergo TKA
  • Fluent and literate in English
  • Able to give consent for themselves based upon the MacArthur Competence Assessment Tool for Clinical Research
  • Able to have a subarachnoid block with only intravenous sedation

Exclusion Criteria:

  • Less than 60 years of age
  • Cognitively impaired to the point where they are unable to give consent for themselves
  • Blindness or partial blindness
  • Pre-existing neurodegenerative conditions
  • Contraindication for subarachnoid block and/or requiring general anesthesia

Study Design

Enrollment

120 participants

Anticipated

Interventions and Outcome Measures

Arms

With Post-Operative Cognitive Dysfunction

Subjects determined to have post-operative cognitive dysfunction based on the results of:

1. 4AT Delirium Test
2. Scoring on :

1. Montreal Cognitive Assessment
2. Oral Trails Test
3. Stroop Test
4. Symbol Digit Modalities Test

All subjects will undergo:

1. Blood sample collection
2. Cerebral spinal fluid collection
3. ERP testing
4. NACC Cognitive Battery
5. Grooved Pegboard testing

Without Post-Operative Cognitive Dysfunction

Subjects determined to not have post-operative cognitive dysfunction based on the results of:

1. 4AT Delirium Test
2. Scoring on :

1. Montreal Cognitive Assessment
2. Oral Trails Test
3. Stroop Test
4. Symbol Digit Modalities Test

All subjects will undergo:

1. Blood sample collection
2. Cerebral spinal fluid collection
3. ERP testing
4. NACC Cognitive Battery
5. Grooved Pegboard testing

Interventions

Montreal Cognitive Assessment

Cognitive evaluation of short term memory, visuospatial abilities, executive functioning, attention, concentration, working memory, language, and orientation to time and place

Stroop Test

Evaluates Processing Speed and Executive Control

4AT Delirium

Screening tool to test for delirium post surgery

Grooved Pegboard

Evaluation testing for dominant and non dominant sensory-motor speed

NACC Cognitive Battery

A series of tests that evaluate attention, concentration, immediate verbal memory, immediate visual memory, discrimination, processing/motor speed, and validity and effort.

ERP Testing

An event-related potential ( ERP) is the measured brain response that is the direct result of a specific sensory, cognitive, or motor event. More formally, it is any stereotyped electrophysiological response to a stimulus. The study of the brain in this way provides a noninvasive means of evaluating brain functioning.

Blood Plasma and Serum sampling

Up to six 4 ml samples of both serum and plasma will be obtained to assess for inflammatory markers.

Cerebral Spinal Fluid Sample

At the time the spinal is placed for anesthetic purposes, 2ml of cerebral spinal fluid will be obtained to assess for inflammatory markers.

Primary outcome measure

  • Blood Interleukin-1 beta (IL-1β) [ Time Frame: Baseline ]
  • Blood Interleukin-1 beta (IL-1β) [ Time Frame: Pre-op (pre-operation) -Visit 2- Day of surgery ]
  • Blood Interleukin-1 beta (IL-1β) [ Time Frame: Post-op Visit 2- In recovery room up to 12 hours post surgery ]
  • Blood Interleukin-1 beta (IL-1β) [ Time Frame: 2 Week Post-op -Visit 4 ]
  • Blood Interleukin-1 beta (IL-1β) [ Time Frame: 6 Week Post-op -Visit 5 ]
  • Blood Tumor necrosis factor alpha (TNF- α) [ Time Frame: Baseline ]
  • Blood Tumor necrosis factor alpha (TNF- α) [ Time Frame: Pre-op- Visit 2- Day of surgery ]
  • Blood Tumor necrosis factor alpha (TNF- α) [ Time Frame: Post-op Visit 2- In recovery room up to 12 hours post surgery ]
  • Blood Tumor necrosis factor alpha (TNF- α) [ Time Frame: 2-week Post-op Visit 4 ]
  • Blood Tumor necrosis factor alpha (TNF- α) [ Time Frame: 6-week Post-op Visit 5 ]
  • Blood Macrophage inflammatory protein-1 alpha (MIP-1alpha) [ Time Frame: Baseline ]
  • Blood Macrophage inflammatory protein-1 alpha (MIP-1alpha) [ Time Frame: Pre-op Visit 2- Day of surgery ]
  • Blood Macrophage inflammatory protein-1 alpha (MIP-1alpha) [ Time Frame: Post-op Visit 2- In recovery room up to 12 hours post surgery ]
  • Blood Macrophage inflammatory protein-1 alpha (MIP-1alpha) [ Time Frame: 2-week Post-op Visit 4 ]
  • Blood Macrophage inflammatory protein-1 alpha (MIP-1alpha) [ Time Frame: 6- week Post-op Visit 5 ]
  • Blood Monocyte chemoattractant protein-1 (MCP-1/CCL2) [ Time Frame: Baseline ]
  • Blood Monocyte chemoattractant protein-1 (MCP-1/CCL2) [ Time Frame: Pre-op Visit 2- Day of surgery ]
  • Blood Monocyte chemoattractant protein-1 (MCP-1/CCL2) [ Time Frame: Post-op Visit 2- In recovery room up to 12 hours post surgery ]
  • Blood Monocyte chemoattractant protein-1 (MCP-1/CCL2) [ Time Frame: 2 week Post-op Visit 4 ]
  • Blood Monocyte chemoattractant protein-1 (MCP-1/CCL2) [ Time Frame: 6 week- Post-op Visit 5 ]
  • Cerebral Spinal Fluid Phosphorylated Tau Protein [ Time Frame: Pre-op Visit 2-Day of surgery ]
  • ERP response amplitude [ Time Frame: 6 Week post-op visit 5 ]
  • ERP response latency [ Time Frame: 6 Week post-op visit 5 ]
  • ERP response amplitude [ Time Frame: 6 Month post-op visit 6 ]
  • ERP response latency [ Time Frame: 6 Month post-op visit 6 ]
  • Stroop Test [ Time Frame: Baseline ]
  • Stroop Test [ Time Frame: Pre-op Visit 2- Day of surgery ]
  • Stroop Test [ Time Frame: 2 Week post-op Visit 4 ]
  • Montreal Cognitive Assessment [ Time Frame: Baseline ]
  • Montreal Cognitive Assessment [ Time Frame: Pre-op Visit 2- Day of surgery ]
  • Blind Montreal Cognitive Assessment [ Time Frame: 48 Hours post-op- Visit 3 ]
  • Montreal Cognitive Assessment [ Time Frame: 2 Week post-op- Visit 4 ]
  • Oral Trail Making Test [ Time Frame: Baseline ]
  • Oral Trail Making Test [ Time Frame: Pre-op Visit 2- Day of surgery ]
  • Oral Trail Making Test [ Time Frame: 48 Hours post-op Visit 3 ]
  • Oral Trail Making Test [ Time Frame: 2- Week post-op Visit 4 ]
  • Symbol Digit Test [ Time Frame: Baseline ]
  • Symbol Digit Test [ Time Frame: Pre-op Visit 2- Day of surgery ]
  • Symbol Digit Test [ Time Frame: 2- Week post-op Visit 4 ]
  • 4 AT Delirium Screening [ Time Frame: Post-op Visit 2- In recovery room up to 12 hours post surgery ]
  • Grooved Pegboard Test [ Time Frame: 6 month post-op Visit 6 ]
  • National Alzheimer's Coordinating Center Cognitive Battery [ Time Frame: 6 month post-op Visit 6 ]

Central Contacts and Locations

Central contacts

Department of Anesthesiology Chair

8653059220rcraft@utmck.edu

Aimee Pehrson, MPH

8653055432apehrson@utmck.edu

Locations

Robert M Craft

Recruiting

Knoxville, Tennessee, United States, 37920

Contacts

Robert M Craft, MD

865-305-9220

Aimee Pehrson, MPH

8653055432apehrson@utmck.edu

Principal Investigator:

Robert Craft, MD

More Information

Sponsor

University of Tennessee Graduate School of Medicine

Last update posted

May 18, 2022

Last verified

May, 2022

Keywords

  • POCD
  • Neuroinflammation

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by University of Tennessee Graduate School of Medicine on 2022-05-18.