Recombinant Human Superoxide Dismutase (rhSOD) and Vascular Reactivity - Tabular View

Tracking Information

First Received Date ^ICMJE

December 9, 2005

Last Updated Date

May 21, 2008

Start Date ^ICMJE

June 2005

Primary Completion Date

Current Primary Outcome Measures ^ICMJE

Forearm blood flow responses to acetylcholine, nitroglycerine and norepinephrine (ratio between intervention and control arm)

Original Primary Outcome Measures ^ICMJE

Same as current

Change History

Complete list of historical versions of study NCT00264186 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

Markers of inflammation and oxidative stress, change in MAP, change in pulse rate, subjective symptoms and body temperature; antibodies against rhSOD

Original Secondary Outcome Measures ^ICMJE

Markers of inflammation and oxidative stress, Δ MAP, Δ pulse rate, subjective symptoms and body temperature; antibodies against rhSOD

Descriptive Information

Brief Title ^ICMJE

Recombinant Human Superoxide Dismutase (rhSOD) and Vascular Reactivity

Official Title ^ICMJE

Impact of rhCu/Zn SOD on Inflammation-Induced Impairment of Vascular Reactivity

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.

Detailed Description

Study Phase

Phase I

Study Type ^ICMJE

Interventional

Study Design ^ICMJE

Allocation:  Randomized
Control:  Placebo Control
Endpoint Classification:  Pharmacokinetics/Dynamics Study
Intervention Model:  Parallel Assignment
Masking:  Double-Blind

Condition ^ICMJE

Inflammation

Intervention ^ICMJE

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)

Study Arms / Comparison Groups

Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Completed

Enrollment ^ICMJE

Completion Date

Primary Completion Date

Eligibility Criteria ^ICMJE

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

Gender

Male

Ages

18 Years to 45 Years

Accepts Healthy Volunteers

Yes

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Location Countries ^ICMJE

Austria

Administrative Information

NCT ID ^ICMJE

NCT00264186

Responsible Party

Study ID Numbers ^ICMJE

LPS-rhSOD

Study Sponsor ^ICMJE

Medical University of Vienna

Collaborators ^ICMJE

Polymun Scientific, Vienna, Austria

Investigators ^ICMJE

Principal Investigator:

Michael Wolzt, MD

Medical University of Vienna

Information Provided By

Medical University of Vienna

Verification Date

May 2008

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP