Recombinant Human Superoxide Dismutase (rhSOD) and Vascular Reactivity
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
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) |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Parallel Assignment Masking: Double-Blind |
| Official Title: | Impact of rhCu/Zn SOD on Inflammation-Induced Impairment of Vascular Reactivity |
- Forearm blood flow responses to acetylcholine, nitroglycerine and norepinephrine (ratio between intervention and control arm)
- Markers of inflammation and oxidative stress, change in MAP, change in pulse rate, subjective symptoms and body temperature; antibodies against rhSOD
| Estimated Enrollment: | 43 |
| Study Start Date: | June 2005 |
Eligibility| Ages Eligible for Study: | 18 Years to 45 Years |
| Genders Eligible for Study: | Male |
| Accepts 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
Contacts and Locations| Austria | |
| Medical University of Vienna - General Hospital of the City of Vienna AKH | |
| Vienna, Austria, 1090 | |
| Principal Investigator: | Michael Wolzt, MD | Medical University of Vienna |
More Information
No publications provided
| ClinicalTrials.gov Identifier: | NCT00264186 History of Changes |
| Other Study ID Numbers: | LPS-rhSOD |
| Study First Received: | December 9, 2005 |
| Last Updated: | May 21, 2008 |
| Health Authority: | Austria: Federal Ministry for Health and Women |
Additional relevant MeSH terms:
|
Inflammation Pathologic Processes Acetylcholine Nitroglycerin Norepinephrine Superoxide Dismutase Vasodilator Agents Cardiovascular Agents Therapeutic Uses Pharmacologic Actions Cholinergic Agonists Cholinergic Agents Neurotransmitter Agents |
Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Sympathomimetics Autonomic Agents Peripheral Nervous System Agents Vasoconstrictor Agents Adrenergic alpha-Agonists Adrenergic Agonists Adrenergic Agents Free Radical Scavengers Antioxidants Protective Agents |
ClinicalTrials.gov processed this record on May 16, 2013