Discovery for Biomarkers and Risk Factors for Postoperative Delirium in Elderly Patients With Spine Surgery

Spinal Disease Clinical Trial

Official title:

Discovery for Biomarkers and Risk Factors for Postoperative Delirium in Elderly Patients With Spine Surgery

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04120272
• Other study ID #: 4-2019-0654
• Status: Recruiting
• Start date: October 21, 2019
• Est. completion date: October 2021

Study information

• Verified date: June 2021
• Source: Yonsei University
• Contact: Bon-Nyeo Koo, MD, PhD
• Phone: 82-2-2228-2422
• Email: koobn[@]yuhs.ac
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Introduction: With the increase of the elderly population, the number of elderly patients undergoing surgery is increasing, and postoperative delirium is 11-51% depending on the type of surgery. In recent cohort studies have shown that delirium might reduce cognitive function and develop dementia.

Since delirium is difficult to treat, the key to treatment is prevention, and about 40% is prevented when prophylactic intervention is applied. However, delirium is difficult to diagnose and difficult to predict, therefore, biomarkers are needed to diagnose and prevention.

Exosome and brain efficiency test(electroencephalogram, and pulse wave test) have the potential of simple biomarkers that can diagnose postoperative delirium and predict cognitive decline.

Purpose: The purpose of this study is to investigate the risk factors affecting delirium in the elderly who have spinal surgery and to search for biomarkers of delirium for early detection and prevention of delirium.

Description:

Method:

1. Study design: This study is a prospective investigation that identifies risk factors for postoperative delirium and searches for predictive biomarkers of delirium.

2. Inclusion criteria / Exclusion Criteria

1. Inclusion criteria

• Elderly patients over 70

• Eligible Surgeries: lumbar spine fusion surgery, posterior cervical spine fusion surgery, or anterior cervical spine fusion surgery

2. Exclusion Criteria

• Patients with cognitive decline according to MMSE-DS outcome criterion

• Patients diagnosed with malignant or benign tumors

• If surgery is scheduled within 2 hours(micro surgery)

• In case of difficulty in communication

• History of brain neurological diseases (brain hemorrhage, stroke, dementia, Parkinson's, cognitive impairment diagnosis, etc.)

• Patients diagnosed with alcoholism or drug addiction

• Patients with surgical complications (post-operative bleeding, high fever over 39 degrees, etc.)

• Patients undergoing re-operation due to surgery-related complications

3. Outcome

1. Primary outcome: Urinary and Blood exosome, stool

2. Secondary outcome: brain function test(electroencephalogram, pulse wave test, and cognitive test)

4. Measurement

1. Delirium: Confusion Assessment Method(CAM), Korean-Delirium Rating Scale-R-98(K-DRS-R-98), Korean Nusing Delirium Scale(Nu-DESC)

2. Cognitive function test: Mini-Mental State Examination-Dementia Screening(MMSE-DS), Montreal Cognitive Assessment(MoCA), Telephone interview for Cognitive Status(TICS)

3. Depression: Geriatric Depression Scale Short Form Version (GDSSF-K)

4. Activity Daily of Living: K-ADL, K-IADL

5. Frail: Korean version of the FRAIL scale

6. Nutrition: Mini Nutritional Assessment-Short Form

7. patient-reported outcomes ; PROMIS-29

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: October 2021
• Est. primary completion date: October 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 70 Years to 100 Years

Eligibility

Inclusion Criteria:

1. Elderly patients over 70

2. Eligible Surgeries: lumbar spine fusion surgery, posterior cervical spine fusion surgery, or anterior cervical spine fusion surgery

Exclusion Criteria:

1. Patients with cognitive decline according to MMSE-DS outcome criterion

2. Patients diagnosed with malignant or benign tumors

3. If surgery is scheduled within 2 hours(micro surgery)

4. In case of difficulty in communication

5. History of brain neurological diseases (brain hemorrhage, stroke, dementia, Parkinson's, cognitive impairment diagnosis, etc.)

6. Patients diagnosed with alcoholism or drug addiction

7. Patients with surgical complications (post-operative bleeding, high fever over 39 degrees, etc.)

8. Patients undergoing re-operation due to surgery-related complications

Related Conditions & MeSH terms

• Delirium
• Spinal Disease
• Spinal Diseases

Intervention

Procedure:
• Spine surgery
Eligible Surgeries: lumbar spine fusion surgery, posterior cervical spine fusion surgery, or anterior cervical spine fusion surgery

Locations

Country	Name	City	State
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Yonsei University

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Exosomes in Urine: Differences in Gene Expression	- Gene expression and expression comparison in exosomes The gene expression difference is determined using the SAM tool and DEseq2, and the Gene Ontology (GO) Database (www.geneontology.org) and the KEGG database (www.genome.jp/kegg) are used to find the correlation between gene functions.; In the case of miRNA, there will be a regulatory function of the coding gene, so for this purpose, an integrative analysis is performed to identify the mRNA-miRNA interaction	Just before surgery
Primary	Exosomes in Urine: Differences in Gene Expression	- Gene expression and expression comparison in exosomes The gene expression difference is determined using the SAM tool and DEseq2, and the Gene Ontology (GO) Database (www.geneontology.org) and the KEGG database (www.genome.jp/kegg) are used to find the correlation between gene functions.; In the case of miRNA, there will be a regulatory function of the coding gene, so for this purpose, an integrative analysis is performed to identify the mRNA-miRNA interaction	just before end of surgery
Primary	Exosomes in Urine: Differences in Gene Expression	- Gene expression and expression comparison in exosomes The gene expression difference is determined using the SAM tool and DEseq2, and the Gene Ontology (GO) Database (www.geneontology.org) and the KEGG database (www.genome.jp/kegg) are used to find the correlation between gene functions.; In the case of miRNA, there will be a regulatory function of the coding gene, so for this purpose, an integrative analysis is performed to identify the mRNA-miRNA interaction	Post operative day 1 (6 AM)
Primary	Exosomes in Urine: Differences in Gene Expression	- Gene expression and expression comparison in exosomes The gene expression difference is determined using the SAM tool and DEseq2, and the Gene Ontology (GO) Database (www.geneontology.org) and the KEGG database (www.genome.jp/kegg) are used to find the correlation between gene functions.; In the case of miRNA, there will be a regulatory function of the coding gene, so for this purpose, an integrative analysis is performed to identify the mRNA-miRNA interaction	Post operative day 1 (6 PM)
Primary	Exosomes in Urine: Differences in Gene Expression	- Gene expression and expression comparison in exosomes The gene expression difference is determined using the SAM tool and DEseq2, and the Gene Ontology (GO) Database (www.geneontology.org) and the KEGG database (www.genome.jp/kegg) are used to find the correlation between gene functions.; In the case of miRNA, there will be a regulatory function of the coding gene, so for this purpose, an integrative analysis is performed to identify the mRNA-miRNA interaction	immediately after onset of delirium
Primary	Exosomes in Urine: Differences in Gene Expression	- Gene expression and expression comparison in exosomes The gene expression difference is determined using the SAM tool and DEseq2, and the Gene Ontology (GO) Database (www.geneontology.org) and the KEGG database (www.genome.jp/kegg) are used to find the correlation between gene functions.; In the case of miRNA, there will be a regulatory function of the coding gene, so for this purpose, an integrative analysis is performed to identify the mRNA-miRNA interaction	7 days after surgery, within hospitalization period
Primary	Exosomes in Blood: Differences in Gene Expression	- Gene expression and expression comparison in exosomes The gene expression difference is determined using the SAM tool and DEseq2, and the Gene Ontology (GO) Database (www.geneontology.org) and the KEGG database (www.genome.jp/kegg) are used to find the correlation between gene functions.; In the case of miRNA, there will be a regulatory function of the coding gene, so for this purpose, an integrative analysis is performed to identify the mRNA-miRNA interaction	Just before surgery
Primary	Exosomes in Blood: Differences in Gene Expression	- Gene expression and expression comparison in exosomes The gene expression difference is determined using the SAM tool and DEseq2, and the Gene Ontology (GO) Database (www.geneontology.org) and the KEGG database (www.genome.jp/kegg) are used to find the correlation between gene functions.; In the case of miRNA, there will be a regulatory function of the coding gene, so for this purpose, an integrative analysis is performed to identify the mRNA-miRNA interaction	just before end of surgery
Primary	Fecal microbiota		just before surgery, on the day of discharge
Secondary	Brain efficiency test(EEG)	- EEG test for brain efficiency Peak-MEF(intermediate rhythm of background EEG spectrum), Peak-Freq, Peak_power, Theta frequency band (4 or more and less than 8) of the left (Fp1) EEG power value (log scale), Left (Fp1) EEG alpha frequency band (8 or more and less than 12) Power value (log scale), Left (Fp1) EEG slow beta band (more than 12 and less than 15) power value (log scale), Left (Fp1) EEG mid-beta frequency band (more than 15 and less than 20) power value (log scale), Fast beta frequency band of the left (Fp1) brain waves (more than 20 and less than 30) power value (log scale), Gamma frequency band (30 or more and 50 or less) power value (log scale) of left (Fp1) brain waves, Peak amplitude of 125 Hz auditory stimulated brain potential (ERP); Left and right average of P2 (maximum) peak value difference based on N1 (minimum) peak. Peak amplitude mean of left (Fp1) auditory induced brain potentials (ERPs), Left and right EEG cross-correlation coefficient.	Before surgery (from 2 weeks before to the day before)
Secondary	Brain efficiency test(pulse wave test)	- pulse wave test for brain efficiency HF (High Frequency) frequency band of heart rate variability (RRV) (0.15 or more and 0.4Hz or less), LF (Low Frequency) frequency band of heart rate variability (RRV) (0.04 or more and less than 0.15 Hz) absolute power, Relative percentage of LF to (LF + HF), Total power of heart rate variability (RRV), Heart rate variability (RRV) histogram; the histogram distribution area divided by the maximum value	Before surgery (from 2 weeks before to the day before)
Secondary	Cognitive test -MMSE		Before surgery (from 2 weeks before to the day before)
Secondary	Cognitive test -MOCA		Before surgery (from 2 weeks before to the day before)
Secondary	Cognitive test -TICS		Before surgery (from 2 weeks before to the day before)
Secondary	Brain efficiency test(EEG)	- EEG test for brain efficiency Peak-MEF(intermediate rhythm of background EEG spectrum), Peak-Freq, Peak_power, Theta frequency band (4 or more and less than 8) of the left (Fp1) EEG power value (log scale), Left (Fp1) EEG alpha frequency band (8 or more and less than 12) Power value (log scale), Left (Fp1) EEG slow beta band (more than 12 and less than 15) power value (log scale), Left (Fp1) EEG mid-beta frequency band (more than 15 and less than 20) power value (log scale), Fast beta frequency band of the left (Fp1) brain waves (more than 20 and less than 30) power value (log scale), Gamma frequency band (30 or more and 50 or less) power value (log scale) of left (Fp1) brain waves, Peak amplitude of 125 Hz auditory stimulated brain potential (ERP); Left and right average of P2 (maximum) peak value difference based on N1 (minimum) peak. Peak amplitude mean of left (Fp1) auditory induced brain potentials (ERPs), Left and right EEG cross-correlation coefficient.	7 days after surgery, within hospitalization period
Secondary	Brain efficiency test(pulse wave test)	- pulse wave test for brain efficiency HF (High Frequency) frequency band of heart rate variability (RRV) (0.15 or more and 0.4Hz or less), LF (Low Frequency) frequency band of heart rate variability (RRV) (0.04 or more and less than 0.15 Hz) absolute power, Relative percentage of LF to (LF + HF), Total power of heart rate variability (RRV), Heart rate variability (RRV) histogram; the histogram distribution area divided by the maximum value	7 days after surgery, within hospitalization period
Secondary	Cognitive test -MMSE		7 days after surgery, within hospitalization period
Secondary	Cognitive test -MOCA		7 days after surgery, within hospitalization period
Secondary	Cognitive test -TICS		7 days after surgery, within hospitalization period
Secondary	Brain efficiency test(EEG)	- EEG test for brain efficiency Peak-MEF(intermediate rhythm of background EEG spectrum), Peak-Freq, Peak_power, Theta frequency band (4 or more and less than 8) of the left (Fp1) EEG power value (log scale), Left (Fp1) EEG alpha frequency band (8 or more and less than 12) Power value (log scale), Left (Fp1) EEG slow beta band (more than 12 and less than 15) power value (log scale), Left (Fp1) EEG mid-beta frequency band (more than 15 and less than 20) power value (log scale), Fast beta frequency band of the left (Fp1) brain waves (more than 20 and less than 30) power value (log scale), Gamma frequency band (30 or more and 50 or less) power value (log scale) of left (Fp1) brain waves, Peak amplitude of 125 Hz auditory stimulated brain potential (ERP); Left and right average of P2 (maximum) peak value difference based on N1 (minimum) peak. Peak amplitude mean of left (Fp1) auditory induced brain potentials (ERPs), Left and right EEG cross-correlation coefficient.	1 month after surgery
Secondary	Brain efficiency test(pulse wave test)	- pulse wave test for brain efficiency HF (High Frequency) frequency band of heart rate variability (RRV) (0.15 or more and 0.4Hz or less), LF (Low Frequency) frequency band of heart rate variability (RRV) (0.04 or more and less than 0.15 Hz) absolute power, Relative percentage of LF to (LF + HF), Total power of heart rate variability (RRV), Heart rate variability (RRV) histogram; the histogram distribution area divided by the maximum value	1 month after surgery
Secondary	Cognitive test -MMSE		1 month after surgery
Secondary	Cognitive test -MOCA		1 month after surgery
Secondary	Cognitive test -TICS		1 month after surgery
Secondary	Brain efficiency test(EEG)	- EEG test for brain efficiency Peak-MEF(intermediate rhythm of background EEG spectrum), Peak-Freq, Peak_power, Theta frequency band (4 or more and less than 8) of the left (Fp1) EEG power value (log scale), Left (Fp1) EEG alpha frequency band (8 or more and less than 12) Power value (log scale), Left (Fp1) EEG slow beta band (more than 12 and less than 15) power value (log scale), Left (Fp1) EEG mid-beta frequency band (more than 15 and less than 20) power value (log scale), Fast beta frequency band of the left (Fp1) brain waves (more than 20 and less than 30) power value (log scale), Gamma frequency band (30 or more and 50 or less) power value (log scale) of left (Fp1) brain waves, Peak amplitude of 125 Hz auditory stimulated brain potential (ERP); Left and right average of P2 (maximum) peak value difference based on N1 (minimum) peak. Peak amplitude mean of left (Fp1) auditory induced brain potentials (ERPs), Left and right EEG cross-correlation coefficient.	1 year after surgery
Secondary	Brain efficiency test(pulse wave test)	- pulse wave test for brain efficiency HF (High Frequency) frequency band of heart rate variability (RRV) (0.15 or more and 0.4Hz or less), LF (Low Frequency) frequency band of heart rate variability (RRV) (0.04 or more and less than 0.15 Hz) absolute power, Relative percentage of LF to (LF + HF), Total power of heart rate variability (RRV), Heart rate variability (RRV) histogram; the histogram distribution area divided by the maximum value	1 year after surgery
Secondary	Cognitive test -MMSE		1 year after surgery
Secondary	Cognitive test -MOCA		1 year after surgery
Secondary	Cognitive test -TICS		1 year after surgery