Liraglutide in Preventing Delirium in Diabetic Elderly After Cardiac Surgery

Perioperative Application of Liraglutide for the Prevention of Postoperative Delirium Among Elderly Patients with Type 2 Diabetes Undergoing Cardiac Surgery: a Single-Center Randomized Controlled Study

This study aims to clarify the preventive effect of perioperative liraglutide application on postoperative delirium in elderly patients with Type 2 diabetes undergoing cardiac surgery.

Study Overview

• Status: Recruiting
• Conditions: Delirium, Postoperative
• Intervention / Treatment: Drug: Liraglutide injection; Drug: Placebo injection

Detailed Description

Delirium is the most prevalent neurological complication following cardiac surgery. It is characterized by an acute and fluctuating disturbance in consciousness, attention, and cognitive function. The incidence of delirium post-cardiac surgery ranges between 11% and 46%. It is closely linked to increased postoperative mortality, extended hospital stays, higher healthcare costs, and long-term cognitive impairment. Currently, it is widely recognized that the development of delirium is influenced by multiple factors, including advanced age, diabetes, surgical and anesthetic techniques, depression, baseline cognitive function, and infections, among others.

Inflammatory responses, crucial for protecting against external or internal threats, can, following surgery, lead to neuroinflammation and neurological damage due to elevated postoperative inflammatory markers and blood-brain barrier disruption. The involvement of microglia and astrocytes, key players in the central nervous system's immune response, has been identified in mediating postoperative delirium, making them potential targets for prevention.

Liraglutide, a Glucagon-like peptide-1 receptor agonist primarily used for treating Type 2 diabetes, has shown promise in mitigating neurocognitive damage associated with diabetes and Alzheimer's disease, suggesting its potential in preventing postoperative delirium in cardiac surgery patients with Type 2 diabetes. Preliminary animal studies and a randomized controlled trial indicate that perioperative liraglutide application could reduce the incidence of postoperative delirium by inhibiting glial activation and the subsequent neuroinflammatory response. However, differences in patient demographics, disease severity, and dosing in previous studies highlight the need for further investigation.

The study aims to investigate whether the perioperative administration of liraglutide can prevent the onset of postoperative delirium in elderly patients with Type 2 diabetes undergoing cardiac surgery. Secondary objectives include assessing the impact on the severity and duration of delirium, cognitive function, anxiety, depression, cardiac function, cardiovascular events, ICU stay, mechanical ventilation duration, and levels of serum markers for brain injury, inflammation, myocardial damage, and cardiac function.

• Study Type: Interventional
• Enrollment (Estimated): 260
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Wenxue Liu, PhD，MD; Phone Number: 15751866806; Email: diligent_hi@163.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Recruiting
      • Wenxue liu
      • Contact: Wenxue NA Liu, MD$PHD; Phone Number: +8615751866806; Email: diligent_hi@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥ 60 years
2. Type 2 diabetes
3. Patients undergoing elective cardiac surgery

Exclusion Criteria:

1. History of neurological or psychiatric disorders, such as schizophrenia, epilepsy, Parkinson's disease, severe dementia, etc
2. Patients with communication difficulties, such as severe visual, auditory, or speech impairments
3. History of central nervous system damage or surgery
4. Cardiac function NYHA Class IV
5. Severe liver dysfunction (Child-Pugh Class C)
6. Severe renal failure requiring renal replacement therapy
7. History of pancreatitis
8. Type 1 diabetes
9. Patients whose blood sugar is difficult to control within 4-8 mmol/L during the screening period
10. Patients with medullary thyroid carcinoma or a family history of it
11. Pregnant or breastfeeding women
12. Intolerance or allergy to liraglutide
13. Previous use of GLP-1A and SGLT2i
14. Patients who refuse to sign the informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Liraglutide Group; Subcutaneous injection of liraglutide	Drug: Liraglutide injection; Subcutaneous injection of liraglutide: 0.6 mg administered the day before surgery, 1.8 mg administered post-anesthesia induction on the day of surgery, followed by 0.6 mg daily for the first three postoperative days.; Other Names: Victoza
Placebo Comparator: Vehicle Group; Subcutaneous injection of vehicle	Drug: Placebo injection; Subcutaneous injection of Placebo: the same volume as liraglutide administrated at the corresponding times.; Other Names: Normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of delirium	Confusion Assessment Method (CAM), or its variant for the Intensive Care Unit, known as CAM-ICU, is the tool used to assess the incidence of delirium. For CAM, the scale ranges from a minimum value of 11 to a maximum of 44, with higher scores indicating a worse outcome. In contrast, CAM-ICU does not utilize a numerical scale; it is a qualitative assessment designed to evaluate confusion without assigning specific values.	One day before surgery and within the first seven days after surgery.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The severity of delirium	The CAM-Severity Scale (CAM-S), available in both short-form and long-form versions, serves as a tool for assessing the severity of delirium. The scale extends from 0 to 7 in its short-form and from 0 to 19 in its long-form. Higher scores on the CAM-S are indicative of more severe outcomes.	One day before surgery and within the first seven days after surgery.
Cognitive function	Minimum Mental State Examination (MMSE) is the tool used to assess cognitive function. The scale extends from 0 to 30, with higher scores indicating a better outcome.	One day before surgery; one week after surgery or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.
Anxiety	Generalized anxiety disorder-7 (GAD-7) is the tool used to assess anxiety. The scale extends from 0 to 21, with higher scores indicating a worse outcome.	One day before surgery; one week after surgery or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.
Depression	Patient Health Questionnaire-9 (PHQ-9) is the tool used to assess depression. The scale extends from 0 to 27, with higher scores indicating a worse outcome.	One day before surgery; one week after surgery or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.
Duration of ICU stay	By retrieving the Hospital Information System and ICU special care sheet	The time from transfer into the ICU to discharge from the ICU, assessed up to 12months.
Mechanical ventilation time	By retrieving the Hospital Information System and ICU special care sheet	The time from tracheal intubation to the removal of the tracheal tube, assessed up to 12months.
Duration of hospital stay	By retrieving the Hospital Information System	The time from hospital admission to discharge, assessed up to 12months.
In-hospital mortality	By retrieving the Hospital Information System	The time from hospital admission to discharge, assessed up to 12months.
Incidence of adverse events	By retrieving the Hospital Information System, ICU special care sheet and follow-up	One day preoperatively to three days Postoperatively.
Rate of major cardiovascular adverse events	By retrieving the Hospital Information System, ICU special care sheet and follow-up	Within 1 year post-surgery (including cardiovascular death, myocardial infarction, and stroke)
Serum levels of NSE	ELISA	One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively
Serum levels of CRP	ELISA	One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively
Serum levels of IL-1α	ELISA	One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively
Serum levels of TNF-α	ELISA	One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively
Serum levels of C3	ELISA	One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively
Serum levels of LDH	ELISA	One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively
Serum levels of CK	ELISA	One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively
Serum levels of CK-MB	ELISA	One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively
Serum levels of AST	ELISA	One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively
Serum levels of cTNT	ELISA	One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively
Serum levels of BNP	ELISA	One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively
Serum levels of C1q	ELISA	One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively
Serum levels of IL-1β	ELISA	One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively
Serum levels of IL-6	ELISA	One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively
Serum levels of S100β	ELISA	One day preoperatively; immediately after admission to ICU; 3 days and 7 days postoperatively
Left Ventricular Posterior Wall Thickness in Diastole (LVPWTd)	The echocardiography is used to assess the LVPWTd.	One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.
Left Ventricular End-Diastolic Dimension (LVDd)	The echocardiography is used to assess the LVDd.	One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.
Left Ventricular End-Systolic Diameter (LVDs)	The echocardiography is used to assess the LVDs.	One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.
Left Atrial Diameter (LAD)	The echocardiography is used to assess the LAD.	One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.
Ejection Fraction (EF)	The echocardiography is used to assess the EF.	One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.
Fractional Shortening (FS)	The echocardiography is used to assess the FS.	One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.
Early Diastolic Velocity/Atrial Diastolic Velocity (E/A)	The echocardiography is used to assess the E/A.	One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.
Interventricular Septum Thickness in Diastolic (IVSTd)	The echocardiography is used to assess the IVSTd.	One day preoperatively; One week postoperatively or at the date of discharge; and at 3 months, 6 months, and 1 year postoperatively.

Collaborators and Investigators

• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Investigators: Principal Investigator: Dongjin Wang, PhD，MD, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2024
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2028

Study Registration Dates

• First Submitted: March 19, 2024
• First Submitted That Met QC Criteria: April 7, 2024
• First Posted (Actual): April 11, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 17, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Liraglutide
• Other Study ID Numbers: 2023-LCYJ-PY-21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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