Intranasal Insulin Improves Postoperative Neurocognitive Disorders in Elderly Patients

NCT05613491 | Unknown

• 1 other identifier: XJTU1AF2022LSK-265
• Study Type: interventional
• Target: 438
• Locations: 1 country
• Sites: 1

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.

Conditions

Postoperative Neurocognitive Disorders

Keywords

postoperative neurocognitive disorders; Intranasal insulin

Outcome Measures

Primary Outcomes (1)

• Incidence of postoperative delirium

  Whether or not postoperative delirium happens

  0-7 days after surgery

Secondary Outcomes (6)

• Incidence of delayed neurocognitive recovery within 30 days after surgery

  0-30 days after surgery

• Incidence of neurocognitive disorders within 1 year after surgery

  30 day-1 year after surgery

• The PND Incidence

  0 day-1 year after surgery

• Intraoperative electroencephalogram parameters

  Surgery day

• the level of Neurocognitive biomarkers

  0 day-1 year after surgery

Study Arms (2)

Intranasal insulin group

EXPERIMENTAL

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

Saline group

PLACEBO COMPARATOR

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

Interventions

Intranasal insulin 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

Also known as: Insulin injection，H10890001,Jiangsu Wanbang Biochemical Medicine Group Co., Ltd

Intranasal insulin group

Intranasal saline 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

Also known as: 0.9% sodium chloride，H20013250,Shanghai Baite Medical Supplies Co., Ltd

Saline group

Eligibility Criteria

• Age: 65 Years+
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• First Affiliated Hospital Xi'an Jiaotong University: lead
• Tang-Du Hospital: collaborator
• Tongji Hospital: collaborator
• Second Hospital of Shanxi Medical University: collaborator
• LanZhou University: collaborator
• Sichuan Provincial People's Hospital: collaborator
• The First Affiliated Hospital of Zhengzhou University: collaborator
• 521 Hospital of NORINCO Group: collaborator

Study Sites (1)

First Affiliated Hospital of Xian Jiaotong University

Xi'an, Shannxi, 029710061, China

RECRUITING

Related Publications (13)

• 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.

  PMID: 30336844 BACKGROUND

• 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.

  PMID: 29133765 BACKGROUND

• 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.

  PMID: 21474666 BACKGROUND

• 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.

  PMID: 32210695 BACKGROUND

• 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.

  PMID: 30381076 BACKGROUND

• 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.

  PMID: 28539885 BACKGROUND

• 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.

  PMID: 26879001 BACKGROUND

• 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.

  PMID: 25374101 BACKGROUND

• 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.

  PMID: 17643054 BACKGROUND

• 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.

  PMID: 29180222 BACKGROUND

• 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.

  PMID: 15288712 BACKGROUND

• 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.

  PMID: 24101698 BACKGROUND

• 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.

  PMID: 25337926 BACKGROUND

MeSH Terms

Interventions

Long-Term Synaptic Depression

Intervention Hierarchy (Ancestors)

Neuronal Plasticity; Nervous System Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Qiang Wang, MD,PHD

  First Affiliated Hospital of Xian JiaotongUniversity

  STUDY CHAIR

Central Study Contacts

Qiang Wang, MD,PHD

CONTACT

0086-18049286968; dr.wangqiang@139.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2022
• First Posted: November 14, 2022
• Study Start: November 7, 2022
• Primary Completion: July 31, 2023
• Study Completion: August 31, 2023
• Last Updated: November 14, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR

Locations

CN (1)