Recombinant Human Superoxide Dismutase (rhSOD) and Vascular Reactivity

This study has been completed.
Sponsor:
Collaborator:
Polymun Scientific, Vienna, Austria
Information provided by:
Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT00264186
First received: December 9, 2005
Last updated: May 21, 2008
Last verified: May 2008
  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

Resource links provided by NLM:


Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:
  • Forearm blood flow responses to acetylcholine, nitroglycerine and norepinephrine (ratio between intervention and control arm)

Secondary Outcome Measures:
  • 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
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00264186

Locations
Austria
Medical University of Vienna - General Hospital of the City of Vienna AKH
Vienna, Austria, 1090
Sponsors and Collaborators
Medical University of Vienna
Polymun Scientific, Vienna, Austria
Investigators
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 April 21, 2014