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

NCT00914576 | Completed DMC

• 1 other identifier: OPHT-101108
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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

Keywords

Endotoxin, Escherichia Coli; Retina; Regional Blood Flow

Outcome Measures

Primary Outcomes (1)

• Retinal blood flow

  1 year

Study Arms (2)

1

ACTIVE COMPARATOR

Drug: Vitamin and mineral supplement; Drug: 100% Oxygen; Drug: Escherichia coli Endotoxin

2

PLACEBO COMPARATOR

Drug: Placebo; Drug: 100% Oxygen; Drug: Escherichia coli Endotoxin

Interventions

Vitamin and mineral supplement 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

Also known as: Vitamac Day

1

Placebo DRUG

2 capsules/day for 14 days

2

100% Oxygen DRUG

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

1; 2

Escherichia coli Endotoxin 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.

Also known as: LPS (US Standard)

1; 2

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Department of Clinical Pharmacology, Medical University of Vienna

Vienna, 1090, Austria

Location

Related Publications (2)

• 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.

  PMID: 25525163 DERIVED

• 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.

  PMID: 24576874 DERIVED

MeSH Terms

Conditions

Escherichia coli Infections

Interventions

Vitamins; Oxygen; endotoxin, Escherichia coli; Lipopolysaccharides

Condition Hierarchy (Ancestors)

Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Micronutrients; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Nutrients; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Chalcogens; Elements; Inorganic Chemicals; Gases; Glycoconjugates; Carbohydrates; Polysaccharides, Bacterial; Polysaccharides; Lipids; Antigens, Bacterial; Antigens; Biological Factors; Endotoxins; Bacterial Toxins; Toxins, Biological

Study Officials

• Gerhard Garhofer, MD

  Department of Clinical Pharmacology, Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: June 3, 2009
• First Posted: June 5, 2009
• Study Start: April 1, 2011
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: July 24, 2013

Record last verified: 2013-07

Locations

AU (1)