| December 9, 2005 |
| May 21, 2008 |
| June 2005 |
| |
| Forearm blood flow responses to acetylcholine, nitroglycerine and norepinephrine (ratio between intervention and control arm) |
| Same as current |
| Complete list of historical versions of study NCT00264186 on ClinicalTrials.gov Archive Site |
| Markers of inflammation and oxidative stress, change in MAP, change in pulse rate, subjective symptoms and body temperature; antibodies against rhSOD |
| Markers of inflammation and oxidative stress, Δ MAP, Δ pulse rate, subjective symptoms and body temperature; antibodies against rhSOD |
| |
| Recombinant Human Superoxide Dismutase (rhSOD) and Vascular Reactivity |
| Impact of rhCu/Zn SOD on Inflammation-Induced Impairment of Vascular Reactivity |
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. |
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| Phase I |
| Interventional |
| Randomized, Double-Blind, Placebo Control, Parallel Assignment, Pharmacokinetics/Dynamics Study |
| Inflammation |
- Drug: 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)
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| Completed |
| 43 |
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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
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| Male |
| 18 Years to 45 Years |
| Yes |
| Contact information is only displayed when the study is recruiting subjects |
| Austria |
| |
| NCT00264186 |
|
| LPS-rhSOD |
| Medical University of Vienna |
| Polymun Scientific, Vienna, Austria |
| Principal Investigator: |
Michael Wolzt, MD |
Medical University of Vienna |
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| Medical University of Vienna |
| May 2008 |
