Intranasal Insulin for Postoperative Delirium in Older Patients With T2DM

N/ANot Yet RecruitingNCT07720479

Weidong Mi210 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

210

Conditions

Postoperative Delirium (POD)

Interventions

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 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.

Eligibility

Sex: ALLMin age: 65 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

Time frame: Postoperative Day 1 to Postoperative Day 7

Secondary Outcomes

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.

Time frame: 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.