Intranasal Insulin Improves Postoperative Neurocognitive Disorders in Elderly Patients

Postoperative Neurocognitive Disorders Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05613491
• Other study ID #: XJTU1AF2022LSK-265
• Status: Recruiting
• Phase: N/A
• Start date: November 7, 2022
• Est. completion date: August 31, 2023

Study information

• Verified date: November 2022
• Source: First Affiliated Hospital Xi'an Jiaotong University
• Contact: Qiang Wang, MD,PHD
• Phone: 0086-18049286968
• Email: dr.wangqiang[@]139.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 438
• Est. completion date: August 31, 2023
• Est. primary completion date: July 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Disease
• Neurocognitive Disorders
• Postoperative Neurocognitive Disorders

Intervention

Drug:
• 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
• 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

Locations

Country	Name	City	State
China	First Affiliated Hospital of Xian Jiaotong University	Xi'an	Shannxi

Sponsors (8)

Lead Sponsor	Collaborator
First Affiliated Hospital Xi'an Jiaotong University	521 Hospital of NORINCO Group, LanZhou University, Second Hospital of Shanxi Medical University, Sichuan Provincial People's Hospital, Tang-Du Hospital, The First Affiliated Hospital of Zhengzhou University, Tongji Hospital

Country where clinical trial is conducted

China, 

References & Publications (13)

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. — View Citation

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

Brünner 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. Erratum in: J Clin Endocrinol Metab. 2016 Oct;101(10 ):3863. — View Citation

Chapman CD, Schiöth 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. Review. — View Citation

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. — View Citation

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. Erratum in: J Alzheimers Dis. 2015;45(4):1269-70. — View Citation

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. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of postoperative delirium	Whether or not postoperative delirium happens	0-7 days after surgery
Secondary	Incidence of delayed neurocognitive recovery within 30 days after surgery	Whether or not delayed neurocognitive recovery happens	0-30 days after surgery
Secondary	Incidence of neurocognitive disorders within 1 year after surgery	Whether or not neurocognitive disorders happens	30 day-1 year after surgery
Secondary	The PND Incidence	Whether or not postoperative neurocognitive disorders happensevents after surgery	0 day-1 year after surgery
Secondary	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
Secondary	the level of Neurocognitive biomarkers	Neurocognitive biomarkers includes amyloid-beta protein and tau protein.	0 day-1 year after surgery
Secondary	ApoE-e4 susceptibility	Whether or not carry ApoE-e4	1 day before surgery