The Effects of Intravenous Heme Arginate on Heme Oxygenase-1 Expression (HO-1) and Oxidative Stress in the Human Heart

Myocardial Ischemia Clinical Trial

Official title:

Pilot Trial: The Effects of Intravenous Heme Arginate on HO-1 Expression and Oxidative Stress in the Human Heart

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02314780
• Other study ID #: HO-1 in the Heart
• Secondary ID: 2013-000887-27
• Status: Completed
• Phase: Phase 2
• Start date: March 29, 2015
• Est. completion date: June 13, 2017

Study information

• Verified date: January 2021
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Ischemia reperfusion injury may be attenuated by HO-1 induction. Our previous data confirmed strong HO-1 induction in peripheral blood cells following heme arginate infusion in healthy humans. Furthermore, we could demonstrate the amelioration of experimental ischemia reperfusion injury in the calf musculature by heme arginate in healthy subjects as measured by functional MRI.

Therefore, we propose that HO-1 induction in the human heart may be a suitable target to mitigate cardiac ischemia-reperfusion injury.

The HO-1 induction will be assessed in a clinical trial by myocardial biopsy prior to and after aortic cross-clamping in subjects with or without preceding heme arginate treatment in two different dosages. The HO-1 expression will also be measured in the clinical trials in peripheral blood mononuclear cells. As additional outcome, levels of myoglobin, creatine-kinase and troponin T and reactive oxygen species will be measured in plasma according to standard laboratory procedures.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: June 13, 2017
• Est. primary completion date: June 13, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 85 Years

Eligibility

Inclusion criteria:

• Signed informed consent

• Men and women aged between 40 and 85 years (inclusive)

• Body mass index < 35 kg/m2

• Ability to communicate well with the investigator in the local language and to understand and comply with the requirements of the study

Exclusion criteria (any of the following):

• Known hypersensitivity to the study drug or any excipients of the drug formulation

• Treatment with another investigational drug within 3 weeks prior to screening

• History or clinical evidence of any disease and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism or excretion of the study drug

• Severe renal failure (glomerula filtration rate < 30 ml/min)

• Moderately or severe impaired left ventricular function (ejection fraction < 40%)

• Moderately or severe impaired right ventricular function

• Systolic pulmonary pressure > 45 mmHg

• Acute or recent (<7 days) myocardial infarction

• Child bearing potential

Related Conditions & MeSH terms

• Ischemia
• Myocardial Ischemia

Intervention

Drug:
• Heme arginate 3mg/kg

• Heme arginate 1mg/kg

• Placebo

Locations

Country	Name	City	State
Austria	Medical University of Vienna	Vienna

Sponsors (3)

Lead Sponsor	Collaborator
Martin Andreas, M.D.	National Bank of Austria, Orphan Medical

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Heme Oxygenase-1 (HO-1) Messenger Ribonucleic Acid (mRNA) Levels (Atrial Tissue)	The right atrial appendage was clamped and cut for cannulation before cardiopulmonary bypass. The tissue samples were snap-frozen in the operating theater after sampling.	intraoperative
Primary	Myocardial HO-1 mRNA Levels (Ventricular Tissue Before Aortic Cross-clamping)	A small biopsy was taken from the right ventricular free wall directly before aortic cross-clamping. The tissue samples were snap-frozen in the operating theater after sampling.	intraoperative
Primary	Myocardial HO-1 mRNA Levels (Ventricular Tissue After Aortic Cross-clamping)	A small biopsy was taken from the right ventricular free wall after aortic clamp release before weaning from cardiopulmonary bypass. The tissue samples were snap-frozen in the operating theater after sampling.	intraoperative
Primary	Myocardial HO-1 Protein Concentrations (Atrial Tissue)	The right atrial appendage was clamped and cut for cannulation before cardiopulmonary bypass.The tissue samples were snap-frozen. Western blot analysis was performed. The amount of HO-1 protein (quantified as pixels under the curve) was evaluated.	intraoperative
Primary	Myocardial HO-1 Protein Concentrations (Ventricular Tissue Before Aortic Cross-clamping)	A small biopsy was taken from the right ventricular free wall directly before aortic cross-clamping. The tissue samples were snap-frozen. Western blot analysis was performed. The amount of HO-1 protein (quantified as pixels under the curve) was evaluated.	intraoperative
Primary	Myocardial HO-1 Protein Concentrations (Ventricular Tissue After Aortic Cross-clamping)	A small biopsy was taken from the right ventricular free wall after aortic clamp release before weaning from cardiopulmonary bypass. The tissue samples were snap-frozen in the operating theater after sampling. Western blot analysis was performed. The amount of HO-1 protein (quantified as pixels under the curve) was evaluated.	intraoperative