The Neuro-epigenetics Biomarkers of Postoperative Delirium in Elderly Patients Undergoing Hip/Knee Replacement

Introduction: Postoperative delirium (POD), an acute, transient, fluctuating disturbance in attention, cognition, and level of consciousness, is a common (15-53%) postoperative complication, and it is associated with longer hospital stays, worse functional outcomes, higher healthcare costs, and increased mortality. However, at the current time, effective prevention and treatment are not only hampered by lack of knowledge about the neuropathogenesis of POD but also by a lack of biomarkers that could predict individual risk and assess diagnosis and severity of POD.

Recent studies have focused on inflammatory markers (IL-1, IL-6, IL-8, IL-10, CRP), Alzheimer's disease-related factors (Tau, Aβ40/42), and nerve injury factors (S100β, NSE), but failed to establishing causality between these markers and POD. Furthermore, these results were contradictory. Previous study of the investigators found that the dysregulation of preoperative microRNA (miR)-146a and miR-181c in cerebrospinal fluid (CSF) and serum was associated with the development and severity of POD. Therefore, the investigators hypothesized these neurimmiRs and other neuro-epigenetics biomarkers might participate in the neuropathogenesis of POD.

Purpose: Aims to search for neuro-epigenetics biomarkers to predict and diagnose POD.

Study Overview

• Status: Recruiting
• Conditions: Postoperative Delirium
• Intervention / Treatment: Procedure: hip/knee replacement

Detailed Description

Method:

1. Study design: This study is a prospective investigation that searches for neuro-epigenetics biomarkers to predict and diagnose POD.
2. Inclusion criteria / Exclusion Criteria

Inclusion criteria: Eligible patients were at least 65 years old and were scheduled to have hip/knee replacement.

Exclusion Criteria:

1. a past medical history of neurological or clinically evident neurovascular disease (e.g., Alzheimer's disease, other forms of dementia, stroke);
2. Patients diagnosed with malignant or benign tumors;
3. Mini-Mental State Examination (MMSE) scores of 26 or less;
4. American Society of Anesthesiologists (ASA) score [a global score that assesses the physical status of patients before surgery, ranging from 1 (normal health) to 5 (moribund)] greater than 3;
5. a history of alcohol abuse and drug dependence;
6. inability to read or severe visual or auditory deficits;
7. unwillingness to comply with the protocol or procedures.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430071
      • Recruiting
      • Zhongnan Hospital of Wuhan University
      • Contact: Mian Peng, doctor; Phone Number: +86 18607151101; Email: sophie_pm@msn.com
      • Contact: Qianwen He, doctor; Phone Number: +8615827481960; Email: mos.cherry@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 100 years (Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients were at least 65 years old and were scheduled to have hip/knee replacement.

Description

Inclusion Criteria: Eligible patients were at least 65 years old and were scheduled to have hip/knee replacement.

Exclusion Criteria:

1. a past medical history of neurological or clinically evident neurovascular disease (e.g., Alzheimer's disease, other forms of dementia, stroke);
2. patients diagnosed with malignant or benign tumors;
3. Mini-Mental State Examination (MMSE) scores of 26 or less;
4. American Society of Anesthesiologists (ASA) score greater than 3;
5. a history of alcohol abuse and drug dependence;
6. inability to read or severe visual or auditory deficits;
7. unwillingness to comply with the protocol or procedures.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Delirium group; Group of patients with postoperative delirium	Procedure: hip/knee replacement; hip/knee replacement
Non delirium group; Group of patients without postoperative delirium	Procedure: hip/knee replacement; hip/knee replacement

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cell-free DNA, cell-free RNA and exosomal RNA level in blood and urine	Cell-free DNA, cell-free RNA and exosomal RNA level in blood and urine of the participants were measured by DNA sequencing or RNA sequencing before surgery.	just before surgery
genome-specific difference between POD and non-POD patients	Compare the exon sequence in blood samples of the participants, as assessed by whole exome sequencing.	just before surgery
candidate cell-free DNA, cell-free RNA and exosomal RNA level in blood and urine	Candidate cell-free DNA, cell-free RNA and exosomal RNA identified in the first outcome were quantified by PCR or RT-PCR on post operative day 1.	post operative day 1
candidate cell-free DNA, cell-free RNA and exosomal RNA level in blood and urine	Candidate cell-free DNA, cell-free RNA and exosomal RNA were quantified by PCR or RT-PCR on post operative day 3.	post operative day 3
candidate cell-free DNA, cell-free RNA and exosomal RNA level in blood and urine	Candidate cell-free DNA, cell-free RNA and exosomal RNA were quantified by PCR or RT-PCR on post operative day 7 or the day after delirium disappeared.	post operative day 7 or the day after delirium disappeared

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delirium assessment - 3-minute Diagnostic Interview for Confusion Assessment Method (3D-CAM)	positive or negative	before surgery (from 1 week before to the day before)
Delirium assessment - 3-minute Diagnostic Interview for Confusion Assessment Method (3D-CAM)	positive or negative	post operative day 1
Delirium severity assessment - Delirium Severity based on 3D-CAM (3D-CAM-S)	ranging from 0 to 7 points	post operative day 1
Delirium subtype assessment - Richmond Agitation-Sedation Scale (RASS)	ranging from -5 to +4 points	post operative day 1
Delirium assessment - 3-minute Diagnostic Interview for Confusion Assessment Method (3D-CAM)	positive or negative	post operative day 3
Delirium severity assessment - Delirium Severity based on 3D-CAM (3D-CAM-S)	ranging from 0 to 7 points	post operative day 3
Delirium subtype assessment - Richmond Agitation-Sedation Scale (RASS)	ranging from -5 to +4 points	post operative day 3
Delirium assessment - 3-minute Diagnostic Interview for Confusion Assessment Method (3D-CAM)	positive or negative	post operative day 7 or the day after delirium disappeared
Delirium severity assessment - Delirium Severity based on 3D-CAM (3D-CAM-S)	ranging from 0 to 7 points	post operative day 7 or the day after delirium disappeared
Delirium subtype assessment - Richmond Agitation-Sedation Scale (RASS)	ranging from -5 to +4 points	post operative day 7 or the day after delirium disappeared

Collaborators and Investigators

• Sponsor: Zhongnan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2021
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: April 20, 2021
• First Submitted That Met QC Criteria: June 10, 2021
• First Posted (Actual): June 11, 2021

Study Record Updates

• Last Update Posted (Actual): August 1, 2023
• Last Update Submitted That Met QC Criteria: July 31, 2023
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Postoperative Complications; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Emergence Delirium
• Other Study ID Numbers: HBRC202004072021014

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