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Oxidative stress has been implicated to play a pathogenic role in many disease processes, especially in age-related disorders such as age-related macular degeneration. 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 effect of the antioxidative properties of a certain drug or vitamin combination is hard to investigate. In the current study, we propose to investigate the effect of Retaron®, a combination of carotoinoids, omega-3-fatty acids, a herbal extract of Aronia, vitamins and trace elements, 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 Retaron®. 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Retaron | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Escherichia coli Endotoxin | Drug | dose: 2 ng/kg bodyweight (corresponding to 20 IU/kg), i.v. bolus on both study days. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Retinal Vascular Reactivity | To investigate the effect of oral antioxidative supplementation (Retaron®) on impaired retinal vascular reactivity after LPS administration. Measurements will be performed using the Dynamic Vessel Analyzer (Imedos, Jena, Germany). | Study day 1 and 2 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Ocular blood flow | To investigate the effect of oral antioxidative supplementation on ocular blood flow during inflammation. Measurements will be performed using Laser Doppler Velocimetry (LDV) and the Blue Field entoptic technique. | Study day 1 and 2 |
| Change in impaired endothelial function |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of clinical Pharmacology, Medical University of Vienna | Vienna | State of Vienna | 1080 | Austria |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15016626 | Background | Kolodjaschna J, Berisha F, Lung S, Schaller G, Polska E, Jilma B, Wolzt M, Schmetterer L. LPS-induced microvascular leukocytosis can be assessed by blue-field entoptic phenomenon. Am J Physiol Heart Circ Physiol. 2004 Aug;287(2):H691-4. doi: 10.1152/ajpheart.01240.2003. Epub 2004 Mar 11. | |
| 18614167 | Background |
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| ID | Term |
|---|---|
| C044101 | endotoxin, Escherichia coli |
| D008070 | Lipopolysaccharides |
| ID | Term |
|---|---|
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D011135 | Polysaccharides, Bacterial |
| D011134 | Polysaccharides |
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| Retaron® | Dietary Supplement | Dosage 1 capsule Retaron® per day.: Lutein 10mg, Zeaxanthin 2mg, Fishoil 500mg (with 250 mg DHA, 30 mg EPA), Vitamin C 100mg, Zinc 10mg, Selen 25µg, Vitamin E 25mg, Taurin 50mg, Aroniaextract 50mg, administered for 14 days |
|
| Placebo | Other | Placebo capsules identical in appearance to Retaron capsules |
|
To investigate the effect of oral vitamins and minerals supplementation on impaired endothelial function caused by E. coli endotoxin as assessed by Laser Doppler Velocimetry, the Blue Field entoptic technique and the Dynamic Vessel Analyzer. |
| Study day 1 and 2 |
| Change in antioxidative capacity | To investigate the antioxidative capacity in the blood by determination of malondialdehyd (MDA) levels | Study day 1 and 2 |
| Kolodjaschna J, Berisha F, Lasta M, Polska E, Fuchsjager-Mayrl G, Schmetterer L. Reactivity of retinal blood flow to 100% oxygen breathing after lipopolysaccharide administration in healthy subjects. Exp Eye Res. 2008 Aug;87(2):131-6. doi: 10.1016/j.exer.2008.05.006. Epub 2008 May 18. |
| 10191237 | Background | Suffredini AF, Hochstein HD, McMahon FG. Dose-related inflammatory effects of intravenous endotoxin in humans: evaluation of a new clinical lot of Escherichia coli O:113 endotoxin. J Infect Dis. 1999 May;179(5):1278-82. doi: 10.1086/314717. |
| 11594942 | Background | Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol. 2001 Oct;119(10):1417-36. doi: 10.1001/archopht.119.10.1417. |
| 16187689 | Background | Violi F, Cangemi R. Antioxidants and cardiovascular disease. Curr Opin Investig Drugs. 2005 Sep;6(9):895-900. |
| D008055 |
| Lipids |
| D000942 | Antigens, Bacterial |
| D000941 | Antigens |
| D001685 | Biological Factors |
| D004731 | Endotoxins |
| D001427 | Bacterial Toxins |
| D014118 | Toxins, Biological |