Recombinant Human Superoxide Dismutase (rhSOD) and Vascular Reactivity
Information source: Medical University of Vienna
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Inflammation
Intervention: LPS 2 ng/kg intravenous (IV) bolus (Drug); rhSOD 82,000 IU (8.2 mg)/min intraarterially (Drug); Norepinephrine 60, 120, 240 pmol/min intraarterially over 5 min/dose level (two times; pre-dose and +3.5 hrs) (Drug); Acetylcholine 6.25, 12.5, 25 nmol/min intraarterially over 3 min/dose level (two times; pre-dose and +3.5 hrs) (Drug); Glyceroltrinitrate (nitroglycerine) 4, 8, 16 nmol/min over 3 min/dose level (two times; pre-dose and +3.5 hrs) (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Medical University of Vienna Official(s) and/or principal investigator(s):
Michael Wolzt, MD, Principal Investigator, Affiliation: Medical University of Vienna
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.
Clinical Details
Official title: Impact of rhCu/Zn SOD on Inflammation-Induced Impairment of Vascular Reactivity
Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double-Blind
Primary outcome: Forearm blood flow responses to acetylcholine, nitroglycerine and norepinephrine (ratio between intervention and control arm)
Secondary outcome: Markers of inflammation and oxidative stress, change in MAP, change in pulse rate, subjective symptoms and body temperature; antibodies against rhSOD
Eligibility
Minimum age: 18 Years.
Maximum age: 45 Years.
Gender(s): Male.
Criteria:
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
Locations and Contacts
Medical University of Vienna - General Hospital of the City of Vienna AKH, Vienna 1090, Austria
Additional Information
Starting date: June 2005
Last updated: May 21, 2008
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