Effect of Antioxidants on Oxygen Induced Vasoconstriction in Lipopolysaccharide (LPS) Induced Inflammatory Model in Humans

NCT ID: NCT00914576

Last Updated: 2013-07-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-30
• Study Completion Date: 2013-07-31

Brief Summary

Oxidative stress has been implicated in playing a pathogenic role in many disease processes, especially in age-related disorders. It has been hypothesized that antioxidative agents such as vitamins and minerals, which are capable of scavenging free radicals, may reduce oxidative stress and may, in turn, be beneficial for patients with age-related disorders. Based on this hypothesis, several different combinations of vitamins have been introduced, all targeting at reducing oxidative stress. However, the in-vivo determination of the antioxidative properties of a certain drug or vitamin combination are hard to determine. In the current study, the researchers propose to investigate the effect of VITAMAC®, a combination of vitamins and minerals, in a systemic in-vivo inflammation model.

In the present study, the infusion of LPS, which is a cell wall component of Gram-negative bacteria and a major mediator in the pathogenesis of septic shock, will be used as a standardized experimental model of systemic inflammation in humans. Given that inflammation is associated with enhanced oxidative stress and widespread endothelial dysfunction, the LPS model is well suitable for determination of the antioxidative effects of VITAMAC®. As a main outcome parameter, the vascular reactivity of retinal vessels to systemic hyperoxia (induced by breathing 100% oxygen) will be tested in presence or absence of the antioxidant combination.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

1

Group Type: ACTIVE_COMPARATOR

Vitamin and mineral supplement

Intervention Type: DRUG

1 capsule/day in the morning for 14 days, containing: Lutein 12mg, Vitamin C 300mg, Zinc 10mg, Ginko Biloba 10mg, Flavonoids 25mg, Fish oil 300mg

Vitamin and mineral supplement

Intervention Type: DRUG

1 capsule/day in the evening for 14 days, containing: Zeaxanthin 5mg, Vitamin E 60mg, Copper 1mg, Selene 20µg, Ginko Biloba 10mg, Flavonoids 25mg, Alpha Lipon acid: 150mg

100% Oxygen

Intervention Type: DRUG

breathing of 100% O2 for 30 minutes on both study days

Escherichia coli Endotoxin

Intervention Type: DRUG

Escherichia coli Endotoxin (LPS, US Standard Reference Endotoxin, dose: 2 ng/kg bodyweight (corresponding to 20 IU/kg), i.v. bolus on both study days.

2

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

2 capsules/day for 14 days

100% Oxygen

Intervention Type: DRUG

breathing of 100% O2 for 30 minutes on both study days

Escherichia coli Endotoxin

Intervention Type: DRUG

Escherichia coli Endotoxin (LPS, US Standard Reference Endotoxin, dose: 2 ng/kg bodyweight (corresponding to 20 IU/kg), i.v. bolus on both study days.

Interventions

Vitamin and mineral supplement

1 capsule/day in the morning for 14 days, containing: Lutein 12mg, Vitamin C 300mg, Zinc 10mg, Ginko Biloba 10mg, Flavonoids 25mg, Fish oil 300mg

Intervention Type: DRUG

Vitamin and mineral supplement

1 capsule/day in the evening for 14 days, containing: Zeaxanthin 5mg, Vitamin E 60mg, Copper 1mg, Selene 20µg, Ginko Biloba 10mg, Flavonoids 25mg, Alpha Lipon acid: 150mg

Intervention Type: DRUG

Placebo

2 capsules/day for 14 days

Intervention Type: DRUG

100% Oxygen

breathing of 100% O2 for 30 minutes on both study days

Intervention Type: DRUG

Escherichia coli Endotoxin

Escherichia coli Endotoxin (LPS, US Standard Reference Endotoxin, dose: 2 ng/kg bodyweight (corresponding to 20 IU/kg), i.v. bolus on both study days.

Intervention Type: DRUG

Other Intervention Names

Vitamac Day; LPS (US Standard)

Eligibility Criteria

Inclusion Criteria

• Men aged between 18 and 35 years, nonsmokers
• Body mass index between 15th and 85th percentile (Must et al. 1991)
• Normal findings in the medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant
• Normal laboratory values unless the investigator considers an abnormality to be clinically irrelevant
• Normal ophthalmic findings, ametropia < 3 Dpt

Exclusion Criteria

• Regular use of medication, abuse of alcoholic beverages, participation in a clinical trial in the 3 weeks preceding the study
• Treatment in the previous 3 weeks with any drug, vitamins and minerals supplements as well
• Symptoms of a clinically relevant illness in the 3 weeks before the first study day
• History of hypersensitivity to the trial drug or to drugs with a similar chemical structure
• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Gerhard Garhofer

Prof. Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gerhard Garhofer, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Clinical Pharmacology, Medical University of Vienna

Locations

Department of Clinical Pharmacology, Medical University of Vienna

Vienna, , Austria

Countries

Austria

References

Told R, Schmidl D, Palkovits S, Boltz A, Gouya G, Wolzt M, Witkowska KJ, Popa-Cherecheanu A, Werkmeister RM, Garhofer G, Schmetterer L. Antioxidative capacity of a dietary supplement on retinal hemodynamic function in a human lipopolysaccharide (LPS) model. Invest Ophthalmol Vis Sci. 2014 Dec 18;56(1):403-11. doi: 10.1167/iovs.14-15581.

Reference Type: DERIVED

PMID: 25525163 (View on PubMed)

Told R, Palkovits S, Schmidl D, Boltz A, Gouya G, Wolzt M, Napora KJ, Werkmeister RM, Popa-Cherecheanu A, Garhofer G, Schmetterer L. Retinal hemodynamic effects of antioxidant supplementation in an endotoxin-induced model of oxidative stress in humans. Invest Ophthalmol Vis Sci. 2014 Apr 7;55(4):2220-7. doi: 10.1167/iovs.13-13784.

Reference Type: DERIVED

PMID: 24576874 (View on PubMed)

Other Identifiers

OPHT-101108

Identifier Type: -

Identifier Source: org_study_id