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

Postoperative Delirium Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04923243
• Other study ID #: HBRC202004072021014
• Status: Recruiting
• Start date: November 3, 2021
• Est. completion date: June 2024

Study information

• Verified date: July 2022
• Source: Zhongnan Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: June 2024
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years to 100 Years

Eligibility

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.

Related Conditions & MeSH terms

• Delirium
• Emergence Delirium
• Postoperative Delirium

Intervention

Procedure:
• hip/knee replacement
hip/knee replacement

Locations

Country	Name	City	State
China	Zhongnan Hospital of Wuhan University	Wuhan	Hubei

Sponsors (1)

Lead Sponsor	Collaborator
Zhongnan Hospital

Country where clinical trial is conducted

China, 

Outcome

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