Endothelial Injury Mechanism in Elderly Patients Undergoing Major Surgery

February 7, 2021 updated by: The First Affiliated Hospital of Anhui Medical University

Endothelial Injury Mechanism of Cognitive Decline and Intervention Study in Elderly Patients Undergoing Major Surgery

The incidence of postoperative cognitive injury is high in elderly patients, especially after major surgery. The relevant pathophysiological mechanisms are still unclear, and the possible mechanisms that have been proposed so far include inflammation, neurotransmitter imbalance and metabolic disorders. In recent years, clinical studies of acute brain dysfunction after vascular endothelial injury have attracted attention.

Degradation of the endothelial glycocalyx layer and subsequent shedding of its constituents is seen as an early marker of endothelial injury, and may increase vascular permeability.Many preclinical and clinical studies have demonstrated an association between inflammatory cytokines such as TNF-α, IL-1β, IL-6, and IL-10 and glycocalyx degradation biomarkers.

The scholars found evidence of plasma endothelial injury after abdominal open surgery in the elderly. Dexmedetomidine could attenuate stress response such as TNF-α, IL-1β and IL-6. Based on the above evidence, we hypothesize that elderly patients experience inflammatory response secondary to surgical traumatic stress after major surgery, greatly increasing the degree of endothelial injury (heparan sulphate and syndecan-1), reducing brain perfusion while increasing Blood-brain barrier permeability (S100B level), promoting the release of cytokines Interleukin-2(IL-2), Interleukin-6(IL-6), tumor necrosis factor-alpha(TNF-α) ,and vascular endothelial growth factor (VEGF) while reducing brain-derived neurotrophic factor(BDNF) synthesis, then leading to postoperative acute spasm. We would test the hypothesis that can reverse these effects and improve cognitive deficits.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
464

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Anhui
      • Hefei, Anhui, China
        • The First Affiliated Hospital of Anhui Medical University
    • Zhejiang
      • Hangzhou, Zhejiang, China
        • Hangzhou Cancer Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

65 years to 90 years (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Written informed consent;
  2. Patients undergoing selective major gastrointestinal surgery with laparoscope and general anesthesia;
  3. Age 65-90 yrs;
  4. Anesthesia Society of American (ASA) Scale II~IV;
  5. Anticipated surgery time 2-6 hrs;

Exclusion Criteria:

  1. Dementia patients（Mini-mental state examination< 20）
  2. Factors existed that affect cognition assessment such as language,visual,and auditory dysfunction；
  3. Unstable metal status and mental disease；
  4. A hematocrit value less than 28%in perioperative period;
  5. Patients with abnormal preoperative inflammatory indicators（Higher white blood cell and C-reactive protein);
  6. Patients undergoing cardiac and neural surgery;
  7. Parkinson's Disease；
  8. Sure or suspected abuse of analgesic and sedation drug.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Dexmedetomidine
0.5μg/kg Dexmedetomidine as initial loading dose is given for 15 minutes before induction of anesthesia, followed by a maintenance infusion of 0.4μg/kg/h and stopped 30 minutes before the surgery over.
Drug: Dexmedetomidine
0.5μg/kg Dexmedetomidine as initial loading dose is given for 15 minutes before induction of anesthesia, followed by a maintenance infusion of 0.4μg/kg/h and stopped 30 minutes before the surgery over.
Placebo Comparator: Controlled
0.5μg/kg Saline as initial loading dose is given for 15 minutes before induction of anesthesia, followed by a maintenance infusion of 0.4μg/kg/h and stopped 30 minutes before the surgery over.
Drug: Saline
0.5μg/kg saline as initial loading dose is given for 15 minutes before induction of anesthesia, followed by a maintenance infusion of 0.4μg/kg/h and stopped 30 minutes before the surgery over.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
The change of incidence of postoperative delirium
Time Frame: The 1st, 2nd and 7th day after the surgery.
Through CAM-ICU to assess the incidence of the postoperative delirium.
The 1st, 2nd and 7th day after the surgery.
The change of incidence of postoperative cognition dysfunction
Time Frame: 1 day Before surgery,the 3rd,7th day after the surgery.
The neuropsychological tests performed at the day before the surgery, the 3rd and 7th day after the surgery respectively.Calculate the difference(ΔX) between the score obtained before surgery and 3 or 7 days after the surgery (there are both positive and negative, we use the absolute value), with this difference( ΔX) divided by the standard deviation（SD）of the difference of the normal population, that is ΔX / SD and it is the Z score.If a patient has two or more than two of the absolute value of Z scores ≥1.96, the postoperative cognition dysfunction(POCD) is exist.
1 day Before surgery,the 3rd,7th day after the surgery.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
endothelial injury levels
Time Frame: 1 day Before surgery,the 1st, 2nd, 3rd,7th day after the surgery.
Plasma of patients was collected to test heparan sulphate and syndecan-1.
1 day Before surgery,the 1st, 2nd, 3rd,7th day after the surgery.
Blood-brain barrier permeability
Time Frame: 1 day Before surgery,the 1st, 2nd, 3rd,7th day after the surgery.
Plasma of patients was collected to test S100B level
1 day Before surgery,the 1st, 2nd, 3rd,7th day after the surgery.
The serum concentrations of BDNF
Time Frame: 1 day Before surgery,the 1st, 2nd, 3rd,7th day after the surgery.
Serum level of brain-derived neurotrophic factor (BDNF) was measured.
1 day Before surgery,the 1st, 2nd, 3rd,7th day after the surgery.
Inflammatory factor
Time Frame: 1 day Before surgery,the 1st, 2nd, 3rd,7th day after the surgery.
Plasma of patients was collected to test cytokines IL-2, IL-6, TNF-α and VEGF level.
1 day Before surgery,the 1st, 2nd, 3rd,7th day after the surgery.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
The First Affiliated Hospital of Anhui Medical University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Hangzhou Cancer Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Xinqi Cheng, PhD, The First Affiliated Hospital of Anhui Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 30, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 31, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 13, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 17, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 21, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 10, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 7, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 7742

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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