Effect of Dexmedetomidine on Brain Homeostasis and Neurocognitive Outcome

NCT04266665 | Completed Phase 4

• 1 other identifier: DexProB
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

Brain tumor surgery is commonly associated with different degrees of preoperative intracranial hypertension and surrounding tumor edema, elicited by tumor underlying pathophysiology. During craniotomy for brain tumor resection maintenance of hemodynamic stability and intracranial homoeostasis is of paramount importance. Disordered hemodynamics or adverse stress may activate the immune inflammation or neuroendocrine responses and lead to a surge of inflammatory mediators and stress hormones, which are implicated in secondary brain insults. Adverse physiological responses caused by intraoperative disordered hemodynamics or surgery-related damage, may lead to some secondary brain injury (such as cerebral edema or cerebral hemorrhage), aggravating damage to brain tissue and affecting the recovery from anesthesia, cognition and prognosis in patients. Prevention of secondary brain injury is a key-endpoint to improve clinical outcomes in glioma patients undergoing craniotomy. Alpha2-adrenoceptor agonists have been widely used for sedation, analgesia and anti-sympathetic actions for many years, but the definite evidence of their potential use as neuroprotectants has so far been confined to animal studies, yet the findings are inconsistent. Dexmedetomidine (DEX) has been demonstrated to be a new type a2 adrenergic receptor (a2-AR) agonist, which can selectively bind with the a1 and a2 adrenergic receptor, and playing a dual role by restraining the activity of sympathetic nervous and stimulating the vagus nerve. Dexmedetomidine (DEX) also plays an important role in in inhibiting inflammatory and neuroendocrine responses. Animal experiments showed that the right must have a dexmedetomidine neuro-protective effect. However, the brain-protective effect of dexmedetomidine in anesthesia of craniotomy resection of glioma has not been reported. Thus, the aim of this study was to explore the effect of dexmedetomidine on perioperative brain protection, as well as cerebral oxygenation and metabolic status aiming to provide a basis for clinical rational drug use in patients undergoing craniotomy resection of glioma.

Conditions

Brain Tumor; Metabolic Disturbance; Inflammatory Response; Oxygen Deficiency

Keywords

dexmedetomidine; brain oxygenation; biomarkers; neuroinflammation; brain metabolism; neurocognitive outcome

Outcome Measures

Primary Outcomes (1)

• Changes in S-100b protein

  Alterations in S-100b (μg/L) after intravenous infusion of equivalent doses of dexmedetomidine or placebo (normal saline)

  End of surgical procedure and 24 hours postoperatively

Secondary Outcomes (8)

• Changes in NSE

  End of surgical procedure and 24 hours postoperatively

• Changes in brain oxygen extraction ratio (O2Erbr)

  10, 30, 60, 120, 240 minutes after commencing the infusion of the tested agent and end of surgical procedure

• Changes in jugular venous oxygen saturation

  10, 30, 60, 120, 240 minutes after commencing the infusion of the tested agent and end of surgical procedure

• Changes in arterio-jugular carbon dioxide difference (AjvCO2)

  10, 30, 60, 120, 240 minutes after commencing the infusion of the tested agent and end of surgical procedure

• Changes in arterio-jugular oxygen difference (AjvDO2)

  10, 30, 60, 120, 240 minutes after commencing the infusion of the tested agent and end of surgical procedure

Other Outcomes (3)

• Changes in Mini-Mental State Exam (MMSE)

  1 week and 1 month after the end of surgical procedure

• Changes in Addenbrooke's Cognitive Exam (ACE III)

  1 week and 1 month after the end of surgical procedure

• Changes in Μontreal Cognitive Assessment (MoCA)

  1 week and 1 month after the end of surgical procedure

Study Arms (2)

Dexmedetomidine

ACTIVE COMPARATOR

Dexmedetomidine 2 μg/ml will be given as bolus 1mg/kg for 10 minutes with a maintenance dose of 0.8μg/kg/h until surgery completion

Drug: Dexmedetomidine

Normal saline

PLACEBO COMPARATOR

Normal saline (NaCl 0.9%) administration will start 10 minutes after anesthesia induction and maintained throughout the surgical procedure.

Other: Normal saline

Interventions

Dexmedetomidine DRUG

Dexmedetomidine 2 μg/ml will be given as bolus 1mg/kg for 10 minutes with a maintenance dose of 0.8μg/kg/h until surgery completion

Also known as: Dexdor

Dexmedetomidine

Normal saline OTHER

Equivalent doses for a solution containing 2mcg/ml of the tested drug calculating for a bolus 1mg/kg for 10 minutes with a maintenance dose of 0.8μg/kg/h until surgery completion

Also known as: NaCl 0.9%

Normal saline

Eligibility Criteria

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

You may qualify if:

• ASA-PS 1-3 (American Society of Anesthesiologists Physical Status classification)
• Scheduled for elective or semi-elective craniotomy for brain tumor resection
• Signed informed consent

You may not qualify if:

• History of craniotomy at the same site
• Morbid obesity
• Delirious person before surgery
• Preoperative heart rate (HR) \<45 beats/min or second or third degree AV block
• Treatment with a-methyldopa, clonidine or other a2-adrenergic agonist
• Pregnancy
• Liver or renal failure

Sponsors & Collaborators

• Georgia Tsaousi: lead

Study Sites (1)

AHEPA University Hospital

Thessaloniki, 54636, Greece

Location

MeSH Terms

Conditions

Brain Neoplasms; Hypoxia; Neuroinflammatory Diseases

Interventions

Dexmedetomidine; Saline Solution; Sodium Chloride

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Inflammation; Pathologic Processes

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Georgia Tsaousi, Professor

  Aristotle University Of Thessaloniki

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: February 2, 2020
• First Posted: February 12, 2020
• Study Start: March 12, 2020
• Primary Completion: October 15, 2023
• Study Completion: November 15, 2023
• Last Updated: March 25, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1)