Inflammation
Conditions
Brief 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.
Interventions
DRUGLPS 2 ng/kg intravenous (IV) bolus
DRUGrhSOD 82,000 IU (8.2 mg)/min intraarterially
DRUGNorepinephrine 60, 120, 240 pmol/min intraarterially over 5 min/dose level (two times; pre-dose and +3.5 hrs)
DRUGAcetylcholine 6.25, 12.5, 25 nmol/min intraarterially over 3 min/dose level (two times; pre-dose and +3.5 hrs)
DRUGGlyceroltrinitrate (nitroglycerine) 4, 8, 16 nmol/min over 3 min/dose level (two times; pre-dose and +3.5 hrs)
Sponsors
Polymun Scientific, Vienna, Austria
Medical University of Vienna
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
DOUBLE
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Forearm blood flow responses to acetylcholine, nitroglycerine and norepinephrine (ratio between intervention and control arm) | — |
Secondary
| Measure | Time frame |
|---|---|
| Markers of inflammation and oxidative stress, change in MAP, change in pulse rate, subjective symptoms and body temperature; antibodies against rhSOD | — |
Countries
Austria
Outcome results
None listed