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The Effect of Melatonin on Ischemia-reperfusion Injury Following Acute Myocardial Infarction

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01172171
Recruitment Status : Completed
First Posted : July 29, 2010
Last Update Posted : January 4, 2017
Information provided by (Responsible Party):
Ismail Gögenür, Herlev Hospital

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Acute Myocardial Infarction Ischemia-reperfusion Injury Drug: Melatonin, N-acetyl-5-methoxytryptamine Drug: Isotonic saline, Natrium chloride Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 41 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Intracoronary Injection of Melatonin for Patients With ST-elevation Myocardial Infarction: a Placebo Controlled Randomized Study
Study Start Date : June 2013
Actual Primary Completion Date : June 2016
Actual Study Completion Date : December 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Attack

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. MRI of the heart [ Time Frame: day 4 after pci (+/- 1 day) ]
    Focusing on quantification infarct size, area at risk and myocardial salvage index

Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. plasma level of melatonin [ Time Frame: after pci ]
    An assessment of the endogenous level of plasma melatonin

  5. Oxidative markers in plasma [ Time Frame: 24 hours after pci ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion criteria:

  • Adults who are able to give informed consent
  • 1 significant coronary occlusion (>2mm) with TIMI 0-1 expected to undergo PCI.
  • The occlusion must be ECG-verified with new ST-elevations ≥ 0.2 mV in V2-V3 and/or ≥ 0.1 in the other leads or a new onset left bundle branch block.
  • Having onset of symptoms of qualifying AMI and undergo PCI within 6 hours.
  • If the patients do not fulfill the ECG inclusion criteria they can still be included if the primary PCI reveals an acute coronary occlusion (>2mm) with TIMI 0-1.

Exclusion criteria:

  • Patients with prior myocardial infarction
  • more than one significant occlusion
  • prehospital thrombolysis
  • known history of renal failure
  • history of autoimmune diseases
  • pregnancy, fertile women or breastfeeding
  • severe concurrent illness with reduced short-term prognosis
  • pacemaker
  • claustrophobia
  • cardiogenic shock
  • metals in the body
  • atrial fibrillation
  • BMI ≥ 40.

Information from the National Library of Medicine

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 identifier (NCT number): NCT01172171

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Aalborg University Hospital
Aalborg, Denmark, 9000
Odense University Hospital
Odense, Denmark, 5000
Sponsors and Collaborators
Herlev Hospital
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Principal Investigator: Ismail L. Gögenur, MD, DSMc Herlev Hospital
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Ismail Gögenür, MD, DMSc, Herlev Hospital Identifier: NCT01172171    
Other Study ID Numbers: NLH-01
First Posted: July 29, 2010    Key Record Dates
Last Update Posted: January 4, 2017
Last Verified: January 2017
Keywords provided by Ismail Gögenür, Herlev Hospital:
Ischemia-reperfusion injury
Acute Myocardial Infarction
Intracoronary melatonin
Additional relevant MeSH terms:
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Myocardial Infarction
Reperfusion Injury
Pathologic Processes
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Postoperative Complications
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Central Nervous System Depressants