Methylene Blue and Postoperative Neurocognitive Disorders

NCT04529265 | Completed DMC

• 1 other identifier: 2008222-Exps
• Study Type: interventional
• Target: 314
• Locations: 1 country
• Sites: 1

Brief Summary

Postoperative Neurocognitive Disorders are the most common neurological complications after major surgery, which are associated with higher increased mortality and morbidity in elderly patients undergoing major surgery. Until now highly effective intervention has not been established yet. Recent preclinical studies suggest neuroinflammation may be linked to pathogensis of (postoperative delirium) POD and postoperative cognitive dysfunction (POCD). As Methylene blue(MB) has neuroprotective and anti-inflammatory properties, and it is a safe drug with long history of clinical use, we propose that inflammation-targeted interventions may be useful to prevent POD/POCD in surgical patients.

Conditions

Postoperative Delirium

Outcome Measures

Primary Outcomes (1)

• Incidence of postoperative delirium(POD)

  the effectiveness of MB in reducing the incidence of POD compared with placebo in patients undergoing pancreatic tumor surgery.

  Participants will be followed for the duration of hospital stay, an expected average of 7 days.

Secondary Outcomes (8)

• type and duration of POD

  Participants will be followed for the duration of hospital stay, an expected average of 7 days

• Safety Assessments: incidence of perioperative adverse events

  the whole perioperative period

• neuroinflammation biomarkers

  on the day of surgery (before anesthesia and at the end of surgery) and postoperative one day

• expressions of inflammatory and adhesion genes in cerebral endothelial cells

  before anesthesia and at first day after surgery

• numbers of PBMCs adhesion to cerebral endothelial cells

  before anesthesia and at first day after surgery

Study Arms (2)

Methylene Blue group

EXPERIMENTAL

The first dosage: 2mg/kg MB diluted with normal saline into total 50 ml volume intravenous administration after induction of anesthesia within one hour; The second dosage: 1mg/kg MB diluted with normal saline into total 50 ml volume intravenous administration before the end of surgery within 30 minutes.

Drug: Methylene Blue

Control group

PLACEBO COMPARATOR

The first dosage: normal saline in total 50 ml volume intravenous administration after induction of anesthesia within one hour; The second dosage: normal saline in total 50 ml volume intravenous administration before the end of surgery within 30 minutes.

Drug: Placebo

Interventions

Methylene Blue DRUG

Intraoperative infusion of 2mg/kg MB after induction of anesthesia for 1 h and 1mg/kg MB with 30 min before the end of surgery

Methylene Blue group

Placebo DRUG

Equal volume of normal saline after induction of anesthesia for 1 h and Equal volume of normal saline within 30 min before the end of surgery

Control group

Eligibility Criteria

• Age: 55 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• aged 55-80 years old
• planning to undergo pancreatic tumor surgery.
• Patients have the ability to act in full spirit, understand and sign the informed consent, and are willing to complete the whole research process.

You may not qualify if:

• preexisted dementia, major depression or other serious mental or neurological disorders
• history of allergy to MB or 6-phospho-glucose dehydrogenase deficiency (favism)
• MMSE\<24
• illiterate patients
• patients diagnosed with rheumatoid diseases such as systemic lupus erythematosus, rheumatoid arthritis and ankylosing spondylitis
• drug or alcohol abuse or recent drug administration that may lead to drug interactions, such as selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs)
• history of major head trauma
• serious medical diseases (ie. heart failure, pulmonary hypertension, acute stage of myocardial infarction or respiratory failure, hepatic and renal dysfunctions)
• severe language, visual or auditory deficiency
• other neoplastic diseases diagnosed in the past 5 years
• participated in other clinical trials within 3 months.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Shanghai Cancer Center, Fudan University

Shanghai, China

Location

Related Publications (6)

• Deng Y, Wang R, Li S, Zhu X, Wang T, Wu J, Zhang J. Methylene blue reduces incidence of early postoperative cognitive disorders in elderly patients undergoing major non-cardiac surgery: An open-label randomized controlled clinical trial. J Clin Anesth. 2021 Feb;68:110108. doi: 10.1016/j.jclinane.2020.110108. Epub 2020 Oct 19.

  PMID: 33091706 BACKGROUND

• Deiner S, Luo X, Lin HM, Sessler DI, Saager L, Sieber FE, Lee HB, Sano M; and the Dexlirium Writing Group; Jankowski C, Bergese SD, Candiotti K, Flaherty JH, Arora H, Shander A, Rock P. Intraoperative Infusion of Dexmedetomidine for Prevention of Postoperative Delirium and Cognitive Dysfunction in Elderly Patients Undergoing Major Elective Noncardiac Surgery: A Randomized Clinical Trial. JAMA Surg. 2017 Aug 16;152(8):e171505. doi: 10.1001/jamasurg.2017.1505. Epub 2017 Aug 16.

  PMID: 28593326 BACKGROUND

• Avidan MS, Maybrier HR, Abdallah AB, Jacobsohn E, Vlisides PE, Pryor KO, Veselis RA, Grocott HP, Emmert DA, Rogers EM, Downey RJ, Yulico H, Noh GJ, Lee YH, Waszynski CM, Arya VK, Pagel PS, Hudetz JA, Muench MR, Fritz BA, Waberski W, Inouye SK, Mashour GA; PODCAST Research Group. Intraoperative ketamine for prevention of postoperative delirium or pain after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial. Lancet. 2017 Jul 15;390(10091):267-275. doi: 10.1016/S0140-6736(17)31467-8. Epub 2017 May 30.

  PMID: 28576285 BACKGROUND

• Tucker D, Lu Y, Zhang Q. From Mitochondrial Function to Neuroprotection-an Emerging Role for Methylene Blue. Mol Neurobiol. 2018 Jun;55(6):5137-5153. doi: 10.1007/s12035-017-0712-2. Epub 2017 Aug 24.

  PMID: 28840449 BACKGROUND

• Gonzalez-Lima F, Barksdale BR, Rojas JC. Mitochondrial respiration as a target for neuroprotection and cognitive enhancement. Biochem Pharmacol. 2014 Apr 15;88(4):584-93. doi: 10.1016/j.bcp.2013.11.010. Epub 2013 Dec 4.

  PMID: 24316434 BACKGROUND

• Wischik CM, Staff RT, Wischik DJ, Bentham P, Murray AD, Storey JM, Kook KA, Harrington CR. Tau aggregation inhibitor therapy: an exploratory phase 2 study in mild or moderate Alzheimer's disease. J Alzheimers Dis. 2015;44(2):705-20. doi: 10.3233/JAD-142874.

  PMID: 25550228 BACKGROUND

MeSH Terms

Conditions

Emergence Delirium

Interventions

Methylene Blue

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)

Phenothiazines; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Jun Zhang, PhD

  Fudan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 22, 2020
• First Posted: August 27, 2020
• Study Start: May 1, 2021
• Primary Completion: April 30, 2023
• Study Completion: December 30, 2024
• Last Updated: May 14, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)