Recombinant Human Superoxide Dismutase (rhSOD) and Vascular Reactivity

Inflammation Clinical Trial

Official title:

Impact of rhCu/Zn SOD on Inflammation-Induced Impairment of Vascular Reactivity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00264186
• Other study ID #: LPS-rhSOD
• Status: Completed
• Phase: Phase 1
• First received: December 9, 2005
• Last updated: May 21, 2008
• Start date: June 2005

Study information

• Verified date: May 2008
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Federal Ministry for Health and Women
• Study type: Interventional

Clinical Trial Summary

Inflammation is characterised by an increased risk for cardiovascular events. Dysfunction of the vascular endothelium caused by oxidative stress might provide a mechanistic link. In acute and chronic inflammation, oxidative stress occurs when the production of reactive oxygen species [ROS] (including superoxide anions [O2-]) exceeds the capacity of the endogenous antioxidant defense systems, resulting in ROS-mediated damage. Recombinant human superoxide dismutase (rhSOD) has shown potent antioxidant properties in in-vitro and animal studies and has been tested in phase I clinical trials in humans. rhSOD could offer a therapeutic option for vascular dysfunction in diseases associated with increased oxidative stress. The investigators, therefore, want to test if the hyporesponsiveness to vasoactive drugs (norepinephrine, acetylcholine and glyceroltrinitrate) during acute inflammation by low-dose lipopolysaccharide (LPS) is due to the increased production of superoxide anions, which could be scavanged by the radical scavenger rhSOD.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Men aged between 18 and 45 years

• Nonsmokers

• Body mass index between 15th and 85th percentile

• Normal findings in medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant

Exclusion Criteria:

• Regular use of medication, abuse of alcoholic beverages, or participation in a clinical trial in the 3 weeks preceding the study

• Evidence of hypertension, pathologic hyperglycemia, or hyperlipidemia

• Treatment in the previous 3 weeks with any drug

• Symptoms of a clinically relevant illness in the 3 weeks before the first study day

• History or presence of gastrointestinal, liver or kidney disease, or other conditions known to interfere with distribution, metabolism or excretion of study drugs

• Blood donation during the previous 3 weeks

• History of hypersensitivity to the trial drug or to drugs with a similar chemical structure

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double-Blind

Related Conditions & MeSH terms

• Inflammation

Intervention

Drug:
• LPS 2 ng/kg intravenous (IV) bolus

• rhSOD 82,000 IU (8.2 mg)/min intraarterially

• Norepinephrine 60, 120, 240 pmol/min intraarterially over 5 min/dose level (two times; pre-dose and +3.5 hrs)

• Acetylcholine 6.25, 12.5, 25 nmol/min intraarterially over 3 min/dose level (two times; pre-dose and +3.5 hrs)

• Glyceroltrinitrate (nitroglycerine) 4, 8, 16 nmol/min over 3 min/dose level (two times; pre-dose and +3.5 hrs)

Locations

Country	Name	City	State
Austria	Medical University of Vienna - General Hospital of the City of Vienna AKH	Vienna

Sponsors (2)

Lead Sponsor	Collaborator
Medical University of Vienna	Polymun Scientific, Vienna, Austria

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Forearm blood flow responses to acetylcholine, nitroglycerine and norepinephrine (ratio between intervention and control arm)
Secondary	Markers of inflammation and oxidative stress, change in MAP, change in pulse rate, subjective symptoms and body temperature; antibodies against rhSOD