Clinical trial NCT02314780: The Effects of Intravenous Heme Arginate on Heme Oxygenase-1 Expression (HO-1) and Oxidative Stress in the Human Heart
Official title: Pilot Trial: The Effects of Intravenous Heme Arginate on HO-1 Expression and Oxidative Stress in the Human Heart
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myocardial Ischemia
Keywords: carboxyhemoglobin
neutrophil
reactive oxygen species
reperfusion injury
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
Collaborators: name: National Bank of Austria
name: Orphan Medical
First posted: 2014-12-11
Enrollment: 31
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Heme Oxygenase-1 (HO-1) Messenger Ribonucleic Acid (mRNA) Levels (Atrial Tissue)
timeFrame: intraoperative
measure: Myocardial HO-1 mRNA Levels (Ventricular Tissue Before Aortic Cross-clamping)
timeFrame: intraoperative
measure: Myocardial HO-1 mRNA Levels (Ventricular Tissue After Aortic Cross-clamping)
timeFrame: intraoperative
measure: Myocardial HO-1 Protein Concentrations (Atrial Tissue)
timeFrame: intraoperative
measure: Myocardial HO-1 Protein Concentrations (Ventricular Tissue Before Aortic Cross-clamping)
timeFrame: intraoperative
measure: Myocardial HO-1 Protein Concentrations (Ventricular Tissue After Aortic Cross-clamping)
timeFrame: intraoperative
Secondary outcomes:
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna
Study officials:
affiliation: Medical University of Vienna
name: Alfred Kocher, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Andreas M, Oeser C, Kainz FM, Shabanian S, Aref T, Bilban M, Messner B, Heidtmann J, Laufer G, Kocher A, Wolzt M. Intravenous Heme Arginate Induces HO-1 (Heme Oxygenase-1) in the Human Heart. Arterioscler Thromb Vasc Biol. 2018 Nov;38(11):2755-2762. doi: 10.1161/ATVBAHA.118.311832.