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

January 26, 2021 updated by: Martin Andreas, M.D.

Pilot Trial: The Effects of Intravenous Heme Arginate on HO-1 Expression 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

31

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Vienna, Austria, 1090
        • Medical University of Vienna

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Heme arginate (high dose)
24 hours prior to the planned surgical aortic valve replacement, heme arginate at a dose of 3 mg/kg diluted to 110ml with 0.9% sodium chloride was administered at a single intravenous infusion using an infusion pump.
Drug: Heme arginate 3mg/kg
Other Names:
  • Normosang
Experimental: Heme arginate (low dose)
24 hours prior to the planned surgical aortic valve replacement, heme arginate at a dose of 1 mg/kg diluted to 110ml with 0.9% sodium chloride was administered at a single intravenous infusion using an infusion pump.
Drug: Heme arginate 1mg/kg
Other Names:
  • Normosang
Placebo Comparator: Placebo
24 hours prior to the planned surgical aortic valve replacement, subjects received a single intravenous infusion of an equivalent volume of 0.9% sodium chloride solution.
Drug: Placebo
Other Names:
  • 0.9% sodium chloride solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
intraoperative
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.
intraoperative
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.
intraoperative
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.
intraoperative
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.
intraoperative
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.
intraoperative

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Martin Andreas, M.D.

Collaborators

National Bank of Austria
Orphan Medical

Investigators

  • Principal Investigator: Alfred Kocher, M.D., Medical University of Vienna

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 29, 2015

Primary Completion (Actual)

June 13, 2017

Study Completion (Actual)

June 13, 2017

Study Registration Dates

First Submitted

December 8, 2014

First Submitted That Met QC Criteria

December 8, 2014

First Posted (Estimate)

December 11, 2014

Study Record Updates

Last Update Posted (Actual)

February 15, 2021

Last Update Submitted That Met QC Criteria

January 26, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HO-1 in the Heart
  • 2013-000887-27 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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