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

NCT01172171 | Completed Phase 2 DMC

• 1 other identifier: NLH-01
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 2

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.

Conditions

Acute Myocardial Infarction; Ischemia-reperfusion Injury

Keywords

Ischemia-reperfusion injury; Acute Myocardial Infarction; Intracoronary melatonin

Outcome Measures

Primary Outcomes (1)

• MRI of the heart

  Focusing on quantification infarct size, area at risk and myocardial salvage index

  day 4 after pci (+/- 1 day)

Secondary Outcomes (5)

• Creatinin Kinase Myocardial Band (CK-MB)

  96 Hours after pci

• Clinical events

  Within 90 days of pci

• High-sensitive Troponin T (Hs-TnT) or High-sensitive TnI

  96 hours after pci

• plasma level of melatonin

  after pci

• Oxidative markers in plasma

  24 hours after pci

Study Arms (2)

Melatonin

ACTIVE COMPARATOR

The randomized patients will receive 10 ml 0,1 mg/ml melatonin intracoronarily and 49 mg intravenously.

Drug: Melatonin, N-acetyl-5-methoxytryptamine

Isotonic saline

PLACEBO COMPARATOR

The randomized patients will receive 10 ml isotonic saline (NaCl)and 490 ml intravenously.

Drug: Isotonic saline, Natrium chloride

Interventions

Melatonin, N-acetyl-5-methoxytryptamine DRUG

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.

Melatonin

Isotonic saline, Natrium chloride DRUG

The randomized patients will be given 10 ml of isotonic saline intracoronarily and 490 ml intravenously.

Isotonic saline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults who are able to give informed consent
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Herlev Hospital: lead

Study Sites (2)

Aalborg University Hospital

Aalborg, Aalborg, 9000, Denmark

Location

Odense University Hospital

Odense, Odense, 5000, Denmark

Location

Related Publications (1)

• Halladin NL, Busch SE, Jensen SE, Hansen HS, Zaremba T, Aaroe J, Rosenberg J, Gogenur I. Intracoronary and systemic melatonin to patients with acute myocardial infarction: protocol for the IMPACT trial. Dan Med J. 2014 Feb;61(2):A4773.

  PMID: 24495883 DERIVED

MeSH Terms

Conditions

Reperfusion Injury

Interventions

Melatonin; Sodium Chloride

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Ismail L. Gögenur, MD, DSMc

  Herlev Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, DMSc

Study Record Dates

• First Submitted: July 28, 2010
• First Posted: July 29, 2010
• Study Start: June 1, 2013
• Primary Completion: June 1, 2016
• Study Completion: December 1, 2016
• Last Updated: January 4, 2017

Record last verified: 2017-01

Locations

DK (2)