Intranasal Insulin Improves Postoperative Neurocognitive Disorders in Elderly Patients

Study Overview
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Brief Summary
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Postoperative neurocognitive disorders (PND) are common postoperative complication of central nervous system, leading to increased risk of the working ability loss after surgery, longer hospital stay, increased medical costs and increased surgical mortality. It is classified as perioperative neurocognitive disorders in mental disorders.Aging is an important demographic characteristic in China, and the elderly is also a population susceptible to PND. There is a lack of targeted prevention and control measures for PND. Central insulin resistance is an important mechanism of cognitive impairment in elderly patients, and exogenous supply of central insulin may be an important measure to improve PND. Compared with conventional subcutaneous and intravenous supply, intranasal insulin administration not only has little effect on blood glucose and insulin levels, but also enters the center through the blood-brain barrier easily and efficiently. Long-term use of intranasal insulin can improve the cognitive function of chronic diseases, but there is a lack of clinical studies on improving PND by intranasal insulin. This study will verify the effectiveness of intranasal insulin in the PND improvement of elderly patients.

Detailed Description
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This study is intended to carry out a large sample, multicenter, double-blind, randomized, placebo, and controlled clinical study. Elderly non diabetes patients undergoing elective extrathoracic, breast, orthopedic, urinary, abdominal, and gynecological operations under general anesthesia are included. They are randomly divided into intranasal insulin group or saline group. Before anesthesia induction, they are given the first nasal spray, once per hour, 20 IU insulin or equal volume saline each time until the end of the operation. Follow up 1 day before operation, 1-7 days after operation, 30 days and 12 months respectively, and evaluate cognition with relevant scales. To verify that compared with the same volume of saline, intranasal insulin can reduce the incidence of postoperative delirium, the incidence of PND 1 year after surgery, and the related cognitive quantitative indicators of ApoE- ɛ4 Gene susceptibility, intraoperative EEG parameters, NfL, IL-6, IL-10, CRP and other biochemical indicators were used to explore the mechanism of intranasal insulin to improve PND.

Official Title
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Intranasal Insulin Improves Postoperative Neurocognitive Disorders in Elderly Patients: a Multicenter, Randomized, Double-blind, Placebo-controlled Study

Conditions
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Postoperative Neurocognitive Disorders

Intervention / Treatment
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* Drug: Intranasal insulin
* Drug: Intranasal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients under general anesthesia through oral intubation; Patients undergoing elective extrathoracic, breast, orthopaedic, urological, abdominal and gynecological operations; Age ≥ 65 years; Cardiac function grade I II (NYHA standard), ASA grade I III; Volunteer for anticipating study and sign an informed consent form; Exclusion Criteria: Diabetes patients; Previous history of craniocerebral and spinal cord trauma, surgery, stroke, and inability to place electrodes on the head; History of nasal cavity stuffiness, epistaxis, rhinitis, and nasopharynx surgery; The operation position is prone and it is difficult to implement intranasal administration; Those who cannot cooperate with the assessment of the scale or have delirium before operation; Preoperative fasting blood glucose<4 mmol/L; Those who have participated in other clinical trials.

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intranasal insulin group<br>Before anesthesia induction, give the first insulin nasal spray, once per hour, 20 IU each time, until the end of the operation | Drug: Intranasal insulin<br>* Put insulin injection into nasal special drug delivery device.Before anesthesia induction, give the first insulin nasal spray, once per hour, 20 IU each time, until the end of the operation<br>* Other names: Insulin injection，H10890001,Jiangsu Wanbang Biochemical Medicine Group Co., Ltd;|
| Placebo Comparator: Saline group<br>Before anesthesia induction, give the equal volumes'saline nasal spray, once per hour, 20 IU each time, until the end of the operation | Drug: Intranasal saline<br>* Put 0.9% sodium chloride into nasal special drug delivery device.Before anesthesia induction, give the first equal volume saline nasal spray, once per hour, 20 IU each time, until the end of the operation<br>* Other names: 0.9% sodium chloride，H20013250,Shanghai Baite Medical Supplies Co., Ltd;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of postoperative delirium | Whether or not postoperative delirium happens | 0-7 days after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of delayed neurocognitive recovery within 30 days after surgery | Whether or not delayed neurocognitive recovery happens | 0-30 days after surgery | 
| Incidence of neurocognitive disorders within 1 year after surgery | Whether or not neurocognitive disorders happens | 30 day-1 year after surgery | 
| The PND Incidence | Whether or not postoperative neurocognitive disorders happensevents after surgery | 0 day-1 year after surgery | 
| Intraoperative electroencephalogram parameters | The intraoperative parameters recorded by electroencephalogram, including BIS occurrence time, the duration with PSI less than 25, spectrum analysis, power spectrum analysis. | Surgery day | 
| the level of Neurocognitive biomarkers | Neurocognitive biomarkers includes amyloid-beta protein and tau protein. | 0 day-1 year after surgery | 
| ApoE-ε4 susceptibility | Whether or not carry ApoE-ε4 | 1 day before surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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postoperative neurocognitive disorders, Intranasal insulin