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Effect of Dexmedetomidine on Brain Homeostasis and Neurocognitive Outcome

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ClinicalTrials.gov Identifier: NCT04266665
Recruitment Status : Recruiting
First Posted : February 12, 2020
Last Update Posted : July 26, 2021
Sponsor:
Information provided by (Responsible Party):
Georgia Tsaousi, Aristotle University Of Thessaloniki

Tracking Information
First Submitted Date  ICMJE February 2, 2020
First Posted Date  ICMJE February 12, 2020
Last Update Posted Date July 26, 2021
Actual Study Start Date  ICMJE March 12, 2020
Estimated Primary Completion Date October 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 10, 2020)
  • Changes in S-100b protein [ Time Frame: End of surgical procedure and 24 hours postoperatively ]
    Alterations in S-100b (μg/L) after intravenous infusion of equivalent doses of dexmedetomidine or placebo (normal saline)
  • Changes in NSE [ Time Frame: End of surgical procedure and 24 hours postoperatively ]
    Alterations in NSE (ng/ml) after intravenous infusion of equivalent doses of dexmedetomidine or placebo (normal saline)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 10, 2020)
  • Changes in serum cortisol [ Time Frame: End of surgical procedure and 24 hours postoperatively ]
    Alterations in serum cortisol (μg/dl) levels after intravenous infusion of equivalent doses of dexmedetomidine or placebo (normal saline)
  • Changes in serum TNF-a [ Time Frame: End of surgical procedure and 24 hours postoperatively ]
    Alterations in serum TNF-a (pg/ml) levels after intravenous infusion of equivalent doses of dexmedetomidine or placebo (normal saline)
  • Changes in serum IL-6 [ Time Frame: End of surgical procedure and 24 hours postoperatively ]
    Alterations in serum IL-6 (pg/ml) levels after intravenous infusion of equivalent doses of dexmedetomidine or placebo (normal saline)
  • Changes in Mini-Mental State Exam (MMSE) [ Time Frame: 1 week and 1 month after the end of surgical procedure ]
    Alterations in Mini-Mental State Exam (MMSE) after intravenous infusion of equivalent doses of dexmedetomidine or placebo (normal saline)
  • Changes in Μontreal Cognitive Assessment (MoCA) [ Time Frame: 1 week and 1 month after the end of surgical procedure ]
    Alterations in Μontreal Cognitive Assessment (MoCA) after intravenous infusion of equivalent doses of dexmedetomidine or placebo (normal saline)
  • Changes in Addenbrooke's Cognitive Exam (ACE III) [ Time Frame: 1 week and 1 month after the end of surgical procedure ]
    Alterations in Addenbrooke's Cognitive Exam (ACE III) after intravenous infusion of equivalent doses of dexmedetomidine or placebo (normal saline)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: February 10, 2020)
  • Changes in jugular venous oxygen saturation [ Time Frame: 10, 30, 60, 120, 240 minutes after commencing the infusion of the tested agent and end of surgical procedure ]
    Alterations in jugular venous oxygen saturation (%), after intravenous infusion of equivalent doses of dexmedetomidine or placebo (normal saline)
  • Changes in arterio-jugular oxygen difference (AjvDO2) [ Time Frame: 10, 30, 60, 120, 240 minutes after commencing the infusion of the tested agent and end of surgical procedure ]
    Alterations in arterio-jugular oxygen difference (AjvDO2 [ml/dl]), after intravenous infusion of equivalent doses of dexmedetomidine or placebo (normal saline)
  • Changes in arterio-jugular carbon dioxide difference (AjvCO2) [ Time Frame: 10, 30, 60, 120, 240 minutes after commencing the infusion of the tested agent and end of surgical procedure ]
    Alterations in arterio-jugular carbon dioxide difference (AjvCO2 [mmHg]), after intravenous infusion of equivalent doses of dexmedetomidine or placebo (normal saline)
  • Changes in brain oxygen extraction ratio (O2Erbr) [ Time Frame: 10, 30, 60, 120, 240 minutes after commencing the infusion of the tested agent and end of surgical procedure ]
    Alterations in brain oxygen extraction ratio (O2Erbr [%]), after intravenous infusion of equivalent doses of dexmedetomidine or placebo (normal saline)
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Effect of Dexmedetomidine on Brain Homeostasis and Neurocognitive Outcome
Official Title  ICMJE Effect of Dexmedetomidine on Brain Homeostasis and Neurocognitive Outcome of Patients Undergoing Brain Tumor Exclusion
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.

Detailed Description

Each participant will receive standard monitoring (ECG, SpO2, SBP, BIS, urine output, temperature). More detailed hemodynamic monitoring will be obtained by Edwards Lifesciences ClearSight system (CO, CI, SV, SVI, SVV, SVR, SVRI).

TCI Propofol and Remifentanil will be the agents of choice for induction and maintenance in anesthesia and cisatracurium will be used for neuromuscular blockade for intubation.

Protective mechanical ventilation will be chosen (7ml/kg IBW) with a respiratory rate to obtain a PaCO2 of 35-40 mmHg. PEEP will be changed for the best PaO2/FiO2 ratio and FiO2 of choice will be 0.5.

The radial artery catheterization will be applied for direct blood pressure measurement and arterial blood gas sampling (pH, PaO2, PaCO2, HCO3, BE, osmolality, lactic acid, Hb, glucose, Na and K will be measured).

The jugular bulb ipsilateral to the craniotomy site will be catheterized for receiving blood samples for blood gas analysis. The following oxygenation and metabolic parameters / derivates will be measured or calculated: SjvO2, pH, PjvO2, PjvCO2, HCO3, BE, Osmolality, Lactic acid jv, Hb, Glucose, Na, K, AjvDO2, AjvCO2, O2ERbr, eRQbr, AjvDL, and LOI.

Dexmedetomidine or normal saline (placebo) administration will start 10 minutes after anesthesia induction and maintained throughout the surgical procedure.

Phases

  • T0: 5 minutes before administration of either DEX or placebo
  • T15: 10 minutes after administration of either DEX or placebo
  • T30: 30 minutes after administration of either DEX or placebo
  • T60: 60 minutes after administration of either DEX or placebo
  • T120: 120 minutes after administration of either DEX or placebo
  • T240: 240 minutes after administration of either DEX or placebo
  • End of surgical procedure Blood samples for measuring S-100b, NSE, cortisol, TNF-a and IL-6 will be obtained at phases T0, end of surgery and 24 hours after administration of either DEX or placebo.

Neurocognitive testing will be performed before surgery, 1 week and 1 month later using Karnofsky Performance Status (KFS), Mini Mental State Exam (MMSE), Μontreal Cognitive Assessment (MoCA) and Addenbrooke's Cognitive Exam (ACE III).

Intraoperative consumption of propofol and remifentanil will also be recorded

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Brain Tumor
  • Metabolic Disturbance
  • Inflammatory Response
  • Oxygen Deficiency
Intervention  ICMJE
  • Drug: Dexmedetomidine
    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
    Other Name: Dexdor
  • Other: Normal saline
    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
    Other Name: NaCl 0.9%
Study Arms  ICMJE
  • Active Comparator: Dexmedetomidine
    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
    Intervention: Drug: Dexmedetomidine
  • Placebo Comparator: Normal saline
    Normal saline (NaCl 0.9%) administration will start 10 minutes after anesthesia induction and maintained throughout the surgical procedure.
    Intervention: Other: Normal saline
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 10, 2020)
56
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 30, 2021
Estimated Primary Completion Date October 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Georgia Tsaousi, Professor +302310994855 tsaousig@otenet.gr
Contact: Anastasia Nikopoulou, MD +302310994862 anastasian1991@windowslive.com
Listed Location Countries  ICMJE Greece
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04266665
Other Study ID Numbers  ICMJE DexProB
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Georgia Tsaousi, Aristotle University Of Thessaloniki
Study Sponsor  ICMJE Georgia Tsaousi
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Georgia Tsaousi, Professor Aristotle University Of Thessaloniki
PRS Account Aristotle University Of Thessaloniki
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP