Heme Arginate in Functional Magnetic Resonance Imaging (fMRI)

Ischemia-reperfusion Injury Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01461512
• Other study ID #: Version 1.2 2008-006967-35
• Status: Active, not recruiting
• Phase: Phase 2
• First received: October 14, 2011
• Last updated: October 26, 2011
• Start date: January 2009
• Est. completion date: December 2011

Study information

• Verified date: October 2011
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Agency for Health and Food Safety
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 16
• Est. completion date: December 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 46 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ischemia
• Ischemia-reperfusion Injury
• Reperfusion Injury

Intervention

Drug:
• heme arginate administration
heme arginate 1 mg/kg body weight 24 hours prior to ischemia
• Placebo administration
NaCl isotonic

Locations

Country	Name	City	State
Austria	Medical University of Vienna, Department of Clinical Pharmacology	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
MWolzt

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	BOLD MRI signal	functional MRI assessment of blood oxygen level dependent signal strength	2 minutes prior to ischemia till 25 minutes after ischemia	No
Primary	Serum markers of myocellular injury	(myoglobin, creatine-kinase)	24 hours after ischemia	Yes
Secondary	Blood pressure	in mmHg	20 minutes prior to and 40 minutes after ischemia	Yes
Secondary	Heart rate	in beats per minute	prior to and after ischemia	Yes