The Effect of Melatonin on Ischemia-reperfusion Injury Following Acute Myocardial Infarction
In Denmark, 12.000 people a year, is struck by acute myocardial infarction. A third of these cannot be saved before treatment is possible.
Despite quick and effective reperfusion of the coronary arteries using PCI (Percutaneous Coronary Intervention) after an acute ST-elevation myocardial infarction, substantial morbidity and mortality remain. Infarct size is an important determinant of the short-and long-term outcome after acute myocardial infarction. The most widely used and most effective proven therapy to limit infarct size is the early reperfusion induced by or PCI.
Although beneficial in terms of myocardial salvage, reperfusion itself may contribute to additional damage of the myocardium; the damage due to the combined processes is known as "ischemia-reperfusion injury". The pathogenesis of myocardial ischemia-reperfusion injury is a multifactorial process involving the interaction of multiple mechanisms. Numerous studies indicate that there are three pivotal factors in the pathogenesis of ischemia-reperfusion injury: elevated oxidative damage, depressed energy metabolism, and altered calcium homeostasis.
Partially reduced species of oxygen, including the superoxide anion radical, hydroxyl radical, and hydrogen peroxide, are generated intracellularly as by-product of oxygen metabolism. These reactive oxygen species cause peroxidation af membrane lipids, denaturation of proteins, and modification of DNA, all of which ultimately can lead to cell death. In mammals, cell damage induced by partially reduced oxygen species can also initiate local inflammatory responses, which then lead to further oxidant-mediated tissue injury.
Melatonin is mainly known for its role as an endogenously produced circadian hormone.
For the last twenty years, increasing evidence has proven melatonin to be a very potent direct and indirect antioxidant.
Recent experimental studies have documented the beneficial effects of melatonin in reducing tissue damage and limiting cardiac pathophysiology in models of experimental ischemia-reperfusion.
Primary hypothesis: Melatonin given to patients undergoing PCI can reduce the myocardial damage sustained by ischemia-reperfusion.
|Acute Myocardial Infarction Ischemia-reperfusion Injury||Drug: Melatonin, N-acetyl-5-methoxytryptamine Drug: Isotonic saline, Natrium chloride||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Investigator)
Primary Purpose: Treatment
|Official Title:||Intracoronary Injection of Melatonin for Patients With ST-elevation Myocardial Infarction: a Placebo Controlled Randomized Study|
- MRI of the heart [ Time Frame: day 4 after pci (+/- 1 day) ]Focusing on quantification infarct size, area at risk and myocardial salvage index
- Creatinin Kinase Myocardial Band (CK-MB) [ Time Frame: 96 Hours after pci ]CK-MB is a cardiac enzyme, which is elevated when the myocardium is damaged.
- Clinical events [ Time Frame: Within 90 days of pci ]Death, sustained ventricular arrhythmias, resuscitation from cardiac arrest, cardiogenic shock, heart failure, major bleedings, stroke, need for revascularization, recurrent ischemia, re-infarctions and re-hospitalization.
- High-sensitive Troponin T (Hs-TnT) or High-sensitive TnI [ Time Frame: 96 hours after pci ]Troponin T/I is a cardiac enzyme, which rises when the myocardium is damaged. To determine whether melatonin treatment reduces infarct size as determined by the concentration of Troponin T/I (area under the curve) in the blood, it will be measured daily for the first 4 days after infarction.
- plasma level of melatonin [ Time Frame: after pci ]An assessment of the endogenous level of plasma melatonin
- Oxidative markers in plasma [ Time Frame: 24 hours after pci ]
|Study Start Date:||June 2013|
|Study Completion Date:||December 2016|
|Primary Completion Date:||June 2016 (Final data collection date for primary outcome measure)|
Active Comparator: Melatonin
The randomized patients will receive 10 ml 0,1 mg/ml melatonin intracoronarily and 49 mg intravenously.
Drug: Melatonin, N-acetyl-5-methoxytryptamine
The investigators will give the randomized patients 10 ml of 0,1 mg/ml melatonin intracoronarily and 490 ml of 0,1 mg/ml (49 mg) melatonin.
Placebo Comparator: Isotonic saline
The randomized patients will receive 10 ml isotonic saline (NaCl)and 490 ml intravenously.
Drug: Isotonic saline, Natrium chloride
The randomized patients will be given 10 ml of isotonic saline intracoronarily and 490 ml intravenously.
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01172171
|Aalborg University Hospital|
|Aalborg, Denmark, 9000|
|Odense University Hospital|
|Odense, Denmark, 5000|
|Principal Investigator:||Ismail L. Gögenur, MD, DSMc||Herlev Hospital|