Intranasal Insulin for Postoperative Delirium in Older Patients With T2DM

NCT07720479 | Not Yet Recruiting DMC

• 2 other identifiers: POD- INI- RCT2026S2026-023-01
• Study Type: interventional
• Target: 210
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Postoperative Delirium (POD)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Postoperative Mild Cognitive Impairment (MCI)

  Postoperative Day 7, 1 Month, and 6 Months

• Postoperative Short-term Memory Impairment

  Postoperative Day 7, 1 Month, and 6 Months

Other Outcomes (2)

• Incidence of Postoperative Adverse Events

  Within 30 days after surgery

• Postoperative Pain Severity (NRS 0-10)

  Daily for the first 7 days after surgery

Study Arms (3)

Intranasal Insulin 40 IU Group

EXPERIMENTAL

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

Intranasal Insulin 80 IU Group

EXPERIMENTAL

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

Control Group

PLACEBO COMPARATOR

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)

Interventions

Insulin, human DRUG

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

Intranasal Insulin 40 IU Group; Intranasal Insulin 80 IU Group

Intranasal Normal Saline (Placebo) DRUG

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.

Control Group

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• 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).
• Severe visual, auditory, or language impairments precluding the completion of neurocognitive assessments.
• American Society of Anesthesiologists (ASA) physical status classification ≥ IV.
• 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.
• 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).
• Known hypersensitivity to insulin or any of its excipients.
• Extremely poor glycemic control (e.g., HbA1c \> 10%), or an episode of severe hypoglycemia or diabetic ketoacidosis within the 3 months prior to enrollment.

Sponsors & Collaborators

• Weidong Mi: lead

MeSH Terms

Conditions

Emergence Delirium

Interventions

Insulin

Condition Hierarchy (Ancestors)

Delirium; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Central Study Contacts

Danyang Geng

CONTACT

17367522284; 1354550512@qq.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor and Chairman, Department of Anesthesiology

Study Record Dates

• First Submitted: June 8, 2026
• First Posted: July 22, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028
• Last Updated: July 22, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share