Clinical trial NCT05613491: Intranasal Insulin Improves Postoperative Neurocognitive Disorders in Elderly Patients
Official title: Intranasal Insulin Improves Postoperative Neurocognitive Disorders in Elderly Patients: a Multicenter, Randomized, Double-blind, Placebo-controlled Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Postoperative Neurocognitive Disorders
Keywords: postoperative neurocognitive disorders
Intranasal insulin
Lead sponsor: First Affiliated Hospital Xi'an Jiaotong University
Sponsor class: OTHER
Collaborators: name: Tang-Du Hospital
name: Tongji Hospital
name: Second Hospital of Shanxi Medical University
name: LanZhou University
name: Sichuan Provincial People's Hospital
name: The First Affiliated Hospital of Zhengzhou University
name: 521 Hospital of NORINCO Group
First posted: 2022-11-14
Enrollment: 438
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of postoperative delirium
timeFrame: 0-7 days after surgery
Secondary outcomes:
measure: Incidence of delayed neurocognitive recovery within 30 days after surgery
timeFrame: 0-30 days after surgery
measure: Incidence of neurocognitive disorders within 1 year after surgery
timeFrame: 30 day-1 year after surgery
measure: The PND Incidence
timeFrame: 0 day-1 year after surgery
measure: Intraoperative electroencephalogram parameters
timeFrame: Surgery day
measure: the level of Neurocognitive biomarkers
timeFrame: 0 day-1 year after surgery
measure: ApoE-ε4 susceptibility
timeFrame: 1 day before surgery
Other outcomes:
Locations:
city: Xi'an
country: China
facility: First Affiliated Hospital of Xian Jiaotong University
state: Shannxi
Study officials:
affiliation: First Affiliated Hospital of Xian JiaotongUniversity
name: Qiang Wang, MD,PHD
role: STUDY_CHAIR
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