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NCT Number: NCT02314780

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

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.

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Key information

Conditions

Myocardial Ischemia Cardiovascular Diseases Heart Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Postoperative Complications Reperfusion Injury Vascular Diseases

Age range

40 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Medical University of Vienna

Vienna, 1090, Austria

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Heme arginate 3mg/kg

Drug

Other names: Normosang

Heme arginate 1mg/kg

Drug

Other names: Normosang

Placebo

Drug

Other names: 0.9% sodium chloride solution

Primary outcomes

  1. Heme Oxygenase-1 (HO-1) Messenger Ribonucleic Acid (mRNA) Levels (Atrial Tissue)

    Time frame: intraoperative

    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.

  2. Myocardial HO-1 mRNA Levels (Ventricular Tissue Before Aortic Cross-clamping)

    Time frame: intraoperative

    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.

  3. Myocardial HO-1 mRNA Levels (Ventricular Tissue After Aortic Cross-clamping)

    Time frame: intraoperative

    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.

  4. Myocardial HO-1 Protein Concentrations (Atrial Tissue)

    Time frame: intraoperative

    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.

  5. Myocardial HO-1 Protein Concentrations (Ventricular Tissue Before Aortic Cross-clamping)

    Time frame: intraoperative

    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.

  6. Myocardial HO-1 Protein Concentrations (Ventricular Tissue After Aortic Cross-clamping)

    Time frame: intraoperative

    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.

Sponsors and collaborators

Lead sponsor

Martin Andreas, M.D.

Other

Collaborators

  • National Bank of Austria
  • Orphan Medical

Registry information

Official study title

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

Important dates

Study start
2015
Primary completion
2017
Study completion
2017
First posted
Dec 11, 2014
Registry last updated
Feb 15, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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