Melatonins Effect on Ischemia-reperfusion Injury Following Acute Myocardial Infarction
Recruitment status was Not yet recruiting
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Purpose
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 thrombolytic therapy 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.
| Condition | Intervention | Phase |
|---|---|---|
|
Acute Myocardial Infarction Ischemia-reperfusion Injury |
Drug: Melatonin, N-acetyl-5-methoxytryptamine Drug: Isotonic saline, Natrium chloride |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, 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: 1 month after surgery ] [ Designated as safety issue: No ]Focusing on quantification of how many cubic milimetres of myocardium still without perfusion (size of necrotic area).
- Creatinin Kinase Myocardial Band (CK-MB) [ Time Frame: 96 Hours ] [ Designated as safety issue: No ]CK-MB is a cardiac enzyme, which is elevated when the myocardium is damaged.
- Clinical events [ Time Frame: Within 90 days of surgery ] [ Designated as safety issue: No ]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.
- Troponin I (TnI) [ Time Frame: 96 hours after surgery ] [ Designated as safety issue: No ]Troponin 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 I (TNI) (area under the curve) in the blood, it will be measured daily for the first 4 days after infarction.
| Estimated Enrollment: | 60 |
| Study Start Date: | October 2011 |
| Estimated Study Completion Date: | May 2013 |
| Estimated Primary Completion Date: | February 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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 Eligibility| Ages Eligible for Study: | 18 Years to 80 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patients with LAD-occlusion expected to undergo PCI
- The LAD-occlusion must be ECG-verified showing ≥ 2 mm ST elevation in 2 anterior or lateral leads V1-V6 and before operation also verified by Coronary Arteriography.
- Having onset of symptoms of qualifying AMI and undergo PCI within 12 hours
- Aged between 18-80 and able to give informed consent
Exclusion Criteria:
- Patients with prior myocardial infarction
- Prehospital thrombolysis
- Known history of renal failure
- History of autoimmune diseases
- Pregnancy and breastfeeding
- Severe concurrent illness with reduced short-term prognosis
- Inability to give informed consent
Contacts and Locations| Contact: Natalie L. Halladin, MD | +45 61 65 14 40 | nathoel@yahoo.dk |
| Contact: Ismail Gögenur, MD, DSc | +4526336426 | ismgog01@heh.regionh.dk |
| Denmark | |
| Gentofte Hospital | Not yet recruiting |
| Hellerup, Copenhagen, Denmark, 2900 | |
| Contact: Natalie L. Halladin, MD +45 61 65 14 40 nathoel@yahoo.dk | |
| Principal Investigator: Natalie L. Halladin, MD | |
| Principal Investigator: | Natalie L. Halladin, MD | Herlev Hospital |
More Information
No publications provided
| Responsible Party: | Natalie L. Halladin/ MD, Herlev Hospital |
| ClinicalTrials.gov Identifier: | NCT01172171 History of Changes |
| Other Study ID Numbers: | NLH-01 |
| Study First Received: | July 28, 2010 |
| Last Updated: | June 15, 2011 |
| Health Authority: | Denmark: The Danish National Committee on Biomedical Research Ethics Denmark: Danish Medicines Agency Denmark: Danish Dataprotection Agency |
Keywords provided by Herlev Hospital:
|
Ischemia-reperfusion injury Acute Myocardial Infarction Intracoronary melatonin |
Additional relevant MeSH terms:
|
Infarction Ischemia Myocardial Infarction Reperfusion Injury Pathologic Processes Necrosis Myocardial Ischemia Heart Diseases Cardiovascular Diseases Vascular Diseases |
Postoperative Complications Melatonin Central Nervous System Depressants Physiological Effects of Drugs Pharmacologic Actions Central Nervous System Agents Therapeutic Uses Antioxidants Molecular Mechanisms of Pharmacological Action Protective Agents |
ClinicalTrials.gov processed this record on May 23, 2013