Clinical trial NCT01461512: Heme Arginate in Functional Magnetic Resonance Imaging (fMRI)
Official title: The Effects of Intravenous Heme Arginate on Functional Magnetic Resonance Imaging During Ischemia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Ischemia-reperfusion Injury
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2011-10-28
Enrollment: 16
Sex: MALE
Minimum age (years): 18
Maximum age (years): 46
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: BOLD MRI signal
timeFrame: 2 minutes prior to ischemia till 25 minutes after ischemia
measure: Serum markers of myocellular injury
timeFrame: 24 hours after ischemia
Secondary outcomes:
measure: Blood pressure
timeFrame: 20 minutes prior to and 40 minutes after ischemia
measure: Heart rate
timeFrame: prior to and after ischemia
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna, Department of Clinical Pharmacology
Study officials:
References:
citation: 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.