Heme Arginate in Functional Magnetic Resonance Imaging (fMRI)

The Effects of Intravenous Heme Arginate on Functional Magnetic Resonance Imaging During Ischemia

Ischemia reperfusion injury may be attenuated by HO-1 induction. Heme arginate showed protective effects during prolonged ischemia in animal studies. Functional blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI) shall evaluate the effects of HO-1 induction during short-time ischemia in skeletal muscle of healthy subjects.

Study Overview

• Status: Unknown
• Conditions: Ischemia-reperfusion Injury
• Intervention / Treatment: Drug: Placebo administration; Drug: heme arginate administration

Detailed Description

Ischemia reperfusion injury may be attenuated by HO-1 induction. Heme arginate showed protective effects during prolonged ischemia in animal studies. The investigators previous data confirmed strong HO-1 induction following heme arginate infusion in healthy humans. Therefore, the investigators next approach is to evaluate the direct effects of heme arginate on short time Ischemia-reperfusion (IR) injury in healthy humans. This will be done by the following surrogate markers of IR injury.

Functional blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI) can measure alterations in tissue oxygenation in a high spatial and temporal resolution. This non-invasive methods therefore represent a promising technique to evaluate the effects of HO-1 induction on energy metabolism and oxygen saturation during ischemic stress and short time reperfusion in skeletal muscle.

As additional outcome, levels of myoglobin and creatine-kinase will be measured in plasma according to standard laboratory procedures.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medical University of Vienna, Department of Clinical Pharmacology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 46 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Signed informed consent
• Men aged between 18 and 46 years (inclusive)
• Nonsmoker for more than 3 months
• Body mass index between 18 and 27 kg/m2
• Normal findings in medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant
• Negative results from urine drug screen if performed
• Ability to communicate well with the investigator in the local language and to understand and comply with the requirements of the study

Exclusion Criteria:

• Known hypersensitivity to the study drug or any excipients of the drug formulation
• Regular use of medication, abuse of alcoholic beverages, participation in a clinical trial in the 3 weeks preceding the study
• 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
• Evidence of hypertension, pathologic hyperglycemia, hyperlipidemia
• Treatment in the previous 3 weeks with any drug including over-the-counter drugs (including herbal medicines such as St John's Wort)
• Symptoms of a clinically relevant illness in the 2 weeks before the first study day
• Blood donation during the previous 3 weeks
• Any metallic, electric, electronic or magnetic device or object not removable
• Claustrophobia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo administration; NaCl isotonic
Experimental: Heme arginate treatment	Drug: heme arginate administration; heme arginate 1 mg/kg body weight 24 hours prior to ischemia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BOLD MRI signal	functional MRI assessment of blood oxygen level dependent signal strength	2 minutes prior to ischemia till 25 minutes after ischemia
Serum markers of myocellular injury	(myoglobin, creatine-kinase)	24 hours after ischemia

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood pressure	in mmHg	20 minutes prior to and 40 minutes after ischemia
Heart rate	in beats per minute	prior to and after ischemia

Collaborators and Investigators

• Sponsor: MWolzt

Publications and helpful links

General Publications

• Andreas M, Schmid AI, Doberer D, Schewzow K, Weisshaar S, Heinze G, Bilban M, Moser E, Wolzt M. Heme arginate improves reperfusion patterns after ischemia: a randomized, placebo-controlled trial in healthy male subjects. J Cardiovasc Magn Reson. 2012 Aug 2;14(1):55. doi: 10.1186/1532-429X-14-55.

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): August 1, 2011
• Study Completion (Anticipated): December 1, 2011

Study Registration Dates

• First Submitted: October 14, 2011
• First Submitted That Met QC Criteria: October 26, 2011
• First Posted (Estimate): October 28, 2011

Study Record Updates

• Last Update Posted (Estimate): October 28, 2011
• Last Update Submitted That Met QC Criteria: October 26, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Postoperative Complications; Ischemia; Reperfusion Injury
• Other Study ID Numbers: Version 1.2 2008-006967-35