Intranasal Insulin Improves Postoperative Neurocognitive Disorders in Elderly Patients

NCT ID: NCT05613491

Last Updated: 2022-11-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

438 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-11-07

Study Completion Date

2023-08-31

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.

Conditions

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Postoperative Neurocognitive Disorders

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

HEALTH_SERVICES_RESEARCH

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Intranasal insulin group

Before anesthesia induction, give the first insulin nasal spray, once per hour, 20 IU each time, until the end of the operation

Group Type EXPERIMENTAL

Intranasal insulin

Intervention Type DRUG

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

Saline group

Before anesthesia induction, give the equal volumes'saline nasal spray, once per hour, 20 IU each time, until the end of the operation

Group Type PLACEBO_COMPARATOR

Intranasal saline

Intervention Type DRUG

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

Interventions

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Intranasal insulin

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

Intervention Type DRUG

Intranasal saline

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

Intervention Type DRUG

Other Intervention Names

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Insulin injection,H10890001,Jiangsu Wanbang Biochemical Medicine Group Co., Ltd 0.9% sodium chloride,H20013250,Shanghai Baite Medical Supplies Co., Ltd

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.
Minimum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Tang-Du Hospital

OTHER

Sponsor Role collaborator

Tongji Hospital

OTHER

Sponsor Role collaborator

Second Hospital of Shanxi Medical University

OTHER

Sponsor Role collaborator

LanZhou University

OTHER

Sponsor Role collaborator

Sichuan Provincial People's Hospital

OTHER

Sponsor Role collaborator

The First Affiliated Hospital of Zhengzhou University

OTHER

Sponsor Role collaborator

521 Hospital of NORINCO Group

OTHER

Sponsor Role collaborator

First Affiliated Hospital Xi'an Jiaotong University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Qiang Wang, MD,PHD

Role: STUDY_CHAIR

First Affiliated Hospital of Xian JiaotongUniversity

Locations

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First Affiliated Hospital of Xian Jiaotong University

Xi'an, Shannxi, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Qiang Wang, MD,PHD

Role: CONTACT

0086-18049286968

Facility Contacts

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Qiang Wang, MD,PHD

Role: primary

0086-18049286968

References

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Evered L, Silbert B, Knopman DS, Scott DA, DeKosky ST, Rasmussen LS, Oh ES, Crosby G, Berger M, Eckenhoff RG; Nomenclature Consensus Working Group. Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery-2018. Br J Anaesth. 2018 Nov;121(5):1005-1012. doi: 10.1016/j.bja.2017.11.087. Epub 2018 Jun 15.

Reference Type BACKGROUND
PMID: 30336844 (View on PubMed)

Liu Y, Xiao W, Meng LZ, Wang TL. Geriatric Anesthesia-related Morbidity and Mortality in China: Current Status and Trend. Chin Med J (Engl). 2017 Nov 20;130(22):2738-2749. doi: 10.4103/0366-6999.218006.

Reference Type BACKGROUND
PMID: 29133765 (View on PubMed)

Evered L, Scott DA, Silbert B, Maruff P. Postoperative cognitive dysfunction is independent of type of surgery and anesthetic. Anesth Analg. 2011 May;112(5):1179-85. doi: 10.1213/ANE.0b013e318215217e. Epub 2011 Apr 7.

Reference Type BACKGROUND
PMID: 21474666 (View on PubMed)

Jayaraj RL, Azimullah S, Beiram R. Diabetes as a risk factor for Alzheimer's disease in the Middle East and its shared pathological mediators. Saudi J Biol Sci. 2020 Feb;27(2):736-750. doi: 10.1016/j.sjbs.2019.12.028. Epub 2019 Dec 26.

Reference Type BACKGROUND
PMID: 32210695 (View on PubMed)

Li X, Run X, Wei Z, Zeng K, Liang Z, Huang F, Ke D, Wang Q, Wang JZ, Liu R, Zhang B, Wang X. Intranasal Insulin Prevents Anesthesia-induced Cognitive Impairments in Aged Mice. Curr Alzheimer Res. 2019;16(1):8-18. doi: 10.2174/1567205015666181031145045.

Reference Type BACKGROUND
PMID: 30381076 (View on PubMed)

Chen Y, Dai CL, Wu Z, Iqbal K, Liu F, Zhang B, Gong CX. Intranasal Insulin Prevents Anesthesia-Induced Cognitive Impairment and Chronic Neurobehavioral Changes. Front Aging Neurosci. 2017 May 10;9:136. doi: 10.3389/fnagi.2017.00136. eCollection 2017.

Reference Type BACKGROUND
PMID: 28539885 (View on PubMed)

Zhang Y, Dai CL, Chen Y, Iqbal K, Liu F, Gong CX. Intranasal Insulin Prevents Anesthesia-Induced Spatial Learning and Memory Deficit in Mice. Sci Rep. 2016 Feb 16;6:21186. doi: 10.1038/srep21186.

Reference Type BACKGROUND
PMID: 26879001 (View on PubMed)

Claxton A, Baker LD, Hanson A, Trittschuh EH, Cholerton B, Morgan A, Callaghan M, Arbuckle M, Behl C, Craft S. Long-acting intranasal insulin detemir improves cognition for adults with mild cognitive impairment or early-stage Alzheimer's disease dementia. J Alzheimers Dis. 2015;44(3):897-906. doi: 10.3233/JAD-141791.

Reference Type BACKGROUND
PMID: 25374101 (View on PubMed)

Benedict C, Hallschmid M, Schultes B, Born J, Kern W. Intranasal insulin to improve memory function in humans. Neuroendocrinology. 2007;86(2):136-42. doi: 10.1159/000106378. Epub 2007 Jul 20.

Reference Type BACKGROUND
PMID: 17643054 (View on PubMed)

Chapman CD, Schioth HB, Grillo CA, Benedict C. Intranasal insulin in Alzheimer's disease: Food for thought. Neuropharmacology. 2018 Jul 1;136(Pt B):196-201. doi: 10.1016/j.neuropharm.2017.11.037. Epub 2017 Nov 24.

Reference Type BACKGROUND
PMID: 29180222 (View on PubMed)

Benedict C, Hallschmid M, Hatke A, Schultes B, Fehm HL, Born J, Kern W. Intranasal insulin improves memory in humans. Psychoneuroendocrinology. 2004 Nov;29(10):1326-34. doi: 10.1016/j.psyneuen.2004.04.003.

Reference Type BACKGROUND
PMID: 15288712 (View on PubMed)

Novak V, Milberg W, Hao Y, Munshi M, Novak P, Galica A, Manor B, Roberson P, Craft S, Abduljalil A. Enhancement of vasoreactivity and cognition by intranasal insulin in type 2 diabetes. Diabetes Care. 2014;37(3):751-9. doi: 10.2337/dc13-1672. Epub 2013 Oct 7.

Reference Type BACKGROUND
PMID: 24101698 (View on PubMed)

Brunner YF, Kofoet A, Benedict C, Freiherr J. Central insulin administration improves odor-cued reactivation of spatial memory in young men. J Clin Endocrinol Metab. 2015 Jan;100(1):212-9. doi: 10.1210/jc.2014-3018.

Reference Type BACKGROUND
PMID: 25337926 (View on PubMed)

Other Identifiers

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XJTU1AF2022LSK-265

Identifier Type: -

Identifier Source: org_study_id

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