Trial | NCT00264186  Report issue

Title

Recombinant Human Superoxide Dismutase (rhSOD) and Vascular Reactivity
Impact of rhCu/Zn SOD on Inflammation-Induced Impairment of Vascular Reactivity

  • Phase

    Phase 1

  • Study Type

    Interventional

  • Status

    Completed No Results Posted

  • Intervention/Treatment

    nitroglycerin norepinephrine lipopolysaccharide acetylcholine chloride recombinant human superoxide dismutase ...

  • Study Participants

    43
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.
Study Started
Jun 30
2005
Last Update
May 22
2008
Estimate

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)

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
No Results Posted