Intranasal Insulin for Postoperative Delirium in Older Patients With T2DM

Intranasal Insulin for Prevention of Postoperative Delirium in Older Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial

Postoperative delirium (POD) is highly prevalent in older patients with type 2 diabetes mellitus (T2DM). Cerebral insulin resistance is considered a key pathophysiological mechanism underlying this association. This study aims to investigate whether intranasal insulin (INI) can prevent POD and early postoperative cognitive decline by improving cerebral insulin resistance. We will conduct a randomized, double-blind, placebo-controlled multicenter trial. Older T2DM patients will be randomly assigned to receive intranasal insulin at doses of 40 IU or 80 IU, or placebo. The primary objective is to evaluate the efficacy of INI in preventing POD and to determine the dose-response relationship.

Study Overview

• Status: Not yet recruiting
• Conditions: Postoperative Delirium (POD)
• Intervention / Treatment: Drug: Insulin, human; Drug: Intranasal Normal Saline (Placebo)

• Study Type: Interventional
• Enrollment (Estimated): 210
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Danyang Geng; Phone Number: 17367522284; Email: 1354550512@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosis of type 2 diabetes mellitus (T2DM) according to the World Health Organization (WHO) criteria.
2. Age ≥ 65 years.
3. Scheduled for elective hepatobiliary tumor resection with an anticipated surgical duration of ≥ 2 hours.
4. Voluntary provision of written informed consent by the patient or their legally authorized representative.

Exclusion Criteria:

1. Preoperative diagnosis of dementia, or an education-adjusted Mini-Mental State Examination (MMSE) score indicating cognitive impairment (illiteracy < 17, primary education < 20, secondary education or above < 24).
2. Severe visual, auditory, or language impairments precluding the completion of neurocognitive assessments.
3. American Society of Anesthesiologists (ASA) physical status classification ≥ IV.
4. History of severe central nervous system disorders (e.g., Parkinson's disease, stroke within the past 6 months, severe traumatic brain injury) or schizophrenia; or chronic use of antipsychotic or antidepressant medications.
5. Nasal anatomical abnormalities or pathologies that may compromise intranasal drug absorption (e.g., severe allergic rhinitis, severe deviated septum, recent nasal trauma or surgery, nasal polyps).
6. Known hypersensitivity to insulin or any of its excipients.
7. Extremely poor glycemic control (e.g., HbA1c > 10%), or an episode of severe hypoglycemia or diabetic ketoacidosis within the 3 months prior to enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intranasal Insulin 40 IU Group; Subjects will receive intranasal insulin treatment at a dose of 20 IU twice daily (totaling 40 IU per day), administered 15 minutes prior to anesthesia induction and continued from postoperative day 1 through postoperative day 7. The scheduled administration time windows are 09:00-10:00 and 16:00-17:00.	Drug: Insulin, human; Subjects will receive intranasal insulin treatment. The specific dosage will vary by study arm: Group 1 receives 40 IU daily (20 IU twice daily), Group 2 receives 80 IU daily (40 IU twice daily), and the control group receives intranasal placebo. Administration occurs 15 minutes prior to anesthesia induction and continues daily from postoperative day 1 through postoperative day 7.Intranasal insulin
Experimental: Intranasal Insulin 80 IU Group; Subjects will receive intranasal insulin treatment at a dose of 40 IU twice daily (totaling 80 IU per day), administered 15 minutes prior to anesthesia induction and continued from postoperative day 1 through postoperative day 7. The scheduled administration time windows are 09:00-10:00 and 16:00-17:00.	Drug: Insulin, human; Subjects will receive intranasal insulin treatment. The specific dosage will vary by study arm: Group 1 receives 40 IU daily (20 IU twice daily), Group 2 receives 80 IU daily (40 IU twice daily), and the control group receives intranasal placebo. Administration occurs 15 minutes prior to anesthesia induction and continues daily from postoperative day 1 through postoperative day 7.Intranasal insulin
Placebo Comparator: Control Group; Subjects will receive intranasal treatment with volume-matched normal saline (20 IU equivalent per spray) twice daily (totaling 80 IU equivalent per day). Administration will occur 15 minutes prior to anesthesia induction and continue from postoperative day 1 through postoperative day 7, during the time windows of 09:00-10:00 and 16:00-17:00.	Drug: Intranasal Normal Saline (Placebo); 0.9% sodium chloride solution for intranasal administration, matched in volume and appearance to the insulin preparation. Administered via the same nasal spray device twice daily (equivalent volume to the 80 IU insulin arm) beginning 15 min before anesthesia induction and continuing postoperatively until POD 7.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative Delirium	The occurrence of postoperative delirium will be assessed using the 3D-CAM (3-Minute Diagnostic Interview for CAM). Assessments will be conducted twice daily (at 09:00-10:00 and 16:00-17:00) from postoperative day 1 through postoperative day 7.	Postoperative Day 1 to Postoperative Day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative Mild Cognitive Impairment (MCI)	Assessment of postoperative mild cognitive impairment (MCI) will be conducted using the Ascertain Dementia 8-item Informant Questionnaire (AD8). The AD8 is a brief screening tool rated by informants (caregivers or family members). A total score of ≥ 2 on the AD8 will indicate the presence of cognitive impairment.	Postoperative Day 7, 1 Month, and 6 Months
Postoperative Short-term Memory Impairment	Short-term memory will be assessed using the Three Words Delayed Recall Test (often referred to as TRT in this study). Patients are asked to recall three unrelated words previously presented. Failure to correctly recall all three words will be considered indicative of short-term memory impairment.	Postoperative Day 7, 1 Month, and 6 Months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Postoperative Adverse Events	Incidence of adverse events within 30 days after surgery, including cardiovascular events, ischemic stroke, pulmonary infection, and acute kidney injury.	Within 30 days after surgery
Postoperative Pain Severity (NRS 0-10)	Postoperative pain severity will be assessed using the Numeric Rating Scale (NRS), ranging from 0 to 10, where 0 indicates "no pain" and 10 represents "the worst imaginable pain".	Daily for the first 7 days after surgery

Collaborators and Investigators

• Sponsor: Weidong Mi

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: June 8, 2026
• First Submitted That Met QC Criteria: July 21, 2026
• First Posted (Actual): July 22, 2026

Study Record Updates

• Last Update Posted (Actual): July 22, 2026
• Last Update Submitted That Met QC Criteria: July 21, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Postoperative Complications; Pathologic Processes; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Emergence Delirium; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins; Insulins; Pancreatic Hormones; Proinsulin; Insulin
• Other Study ID Numbers: POD- INI- RCT2026; S2026-023-01 (Other Identifier: Ethics Committee of the Chinese PLA General Hospital)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (including demographic data, intraoperative parameters, blood glucose levels, 3D-CAM scores, AD8 scores, and adverse events) will be shared. Data will be made available to researchers upon reasonable request after trial completion and approval by the corresponding author. A data use agreement may be required to ensure responsible use.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No