Dexmedetomidine Effect on Mitochondrial Function
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|ClinicalTrials.gov Identifier: NCT02299063|
Recruitment Status : Unknown
Verified May 2018 by James O'Leary, The Hospital for Sick Children.
Recruitment status was: Recruiting
First Posted : November 24, 2014
Last Update Posted : May 9, 2018
|Condition or disease||Intervention/treatment||Phase|
|Complication of Anesthesia Ischaemia-reperfusion Injury||Drug: Dexmedetomidine Drug: 0.9% NaCl||Phase 4|
PICO: For children with non cyanotic congenital heart defects having corrective heart surgery (P) does intraoperative dexmedetomidine (I) reduce real-time changes in mitochondrial function and content (O) compared with children not receiving dexmedetomidine (C).
The study drug (dexmedetomidine or placebo) will be mixed in a standardized syringe of 4mcg/mL for active syringes or 50mL 0.9% sodium chloride for placebo. Blinded syringes will be prepared by the Research Support Pharmacy.
Administration is via the existing central venous line. A bolus dose of 0.125mL/kg (0.5 mcg/kg dexmedetomidine) infused over 10 minutes will be administered, followed by a continuous infusion for the duration of the surgery. The dexmedetomidine/placebo continuous infusion (CI) dose will run at 0.15mL/kg/hr (0.6 mcg/kg/hr dexmedetomidine).
Blood samples will be obtained from each child at three points in the operating room: 1) after the induction of anesthesia, 2) at the first separation from CPB (prior to administration of blood products), and 3) at the end of the surgery.
Samples obtained will be analyzed for mitochondrial function and morphology, total cellular mitochondrial biomass, and mitochondrial deoxyribonucleic acid (mtDNA) damage:
- After isolating lymphocytes, we will use high content imaging (HCI) to assess mitochondrial function and morphology. The lymphocytes will be stained with tetramethylrhodamine methyl ester (TMRM), which stains mitochondria in proportion to mitochondrial membrane potential, giving a metric for mitochondrial function. In addition, the cells will be stained with MitoTracker Green®, which can be used to assess mitochondrial morphology. Mitochondrial morphology will be quantified in a non-biased fashion using a mathematical image analysis algorithm.
- After extraction of genomic DNA, total cellular mitochondrial biomass and mitochondrial DNA damage will be measured using traditional and long-patch quantitative polymerase chain reaction (PCR).
Myocardial tissue will be also collected prior to closure of the atriotomy. Samples will be placed into 3% buffered glutaraldehyde at the time of biopsy, and imaging of mitochondrial structure using electron microscopy will be performed.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||The Protective Effect of the α2-agonist Dexmedetomidine on Mitochondrial Structure and Function for Children With Non-cyanotic Congenital Heart Defects Having Cardiac Surgery: A Randomized Controlled Trial.|
|Study Start Date :||November 2014|
|Estimated Primary Completion Date :||December 2019|
|Estimated Study Completion Date :||December 2019|
Placebo Comparator: Placebo (0.9% Saline)
0.9% Saline: bolus dose of 0.125mL/kg infused over 10 minutes, followed by a continuous infusion (CI) dose at 0.15mL/kg/hr for the duration of surgery.
Drug: 0.9% NaCl
Other Name: Normal Saline
Dexmedetomidine: bolus dose of 0.5 mcg/kg infused over 10 minutes, followed by a continuous infusion (CI) dose at 0.6 mcg/kg/hr for the duration of surgery.
A bolus dose of 0.5 mcg/kg infused over 10 minutes will be administered, followed by a continuous infusion for the duration of the surgery at 0.6 mcg/kg/hr.
Other Name: Precedex
- Mitochondrial function (use high content imaging (HCI) [ Time Frame: Intraoperative ]The primary outcomes for mitochondria will be grouped into mitochondrial function, morphology, content and mtDNA damage.
- Creatinine level (Marker of acute renal injury) [ Time Frame: Postoperative day 1 ]Marker of acute renal injury
- Cardiac function (Left ventricular ejection fraction measured by trans-thoracic echocardiography) [ Time Frame: Postoperative day 1 ]Left ventricular ejection fraction measured by trans-thoracic echocardiography
- Inotropes and vasopressors (Duration and dose of inotropes and vasopressors after surgery) [ Time Frame: Postoperative day 1 ]Duration and dose of inotropes and vasopressors after surgery
- Analgesic effects (Morphine equivalent dose of narcotics consumed) [ Time Frame: Perioperative (from induction of anesthesia for 24 hours) ]Morphine equivalent dose of narcotics consumed
- Sedative effects (Duration of intubation) [ Time Frame: Perioperative (from induction of anesthesia for 24 hours) ]Duration of intubation.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02299063
|Contact: James D O'Leary, MBBCh||(416) 813-1500 ext firstname.lastname@example.org|
|Hospital for Sick Children||Recruiting|
|Toronto, Ontario, Canada, M5G1X8|
|Principal Investigator: James D O'Leary, MBBCh|
|Sub-Investigator: John Coles, MD|
|Sub-Investigator: Jason T Maynes, MD PhD|
|Sub-Investigator: Daniel Stocki|
|Principal Investigator:||James D O'Leary, MBBCh||The Hospital for Sick Children|