Effect of Retaron® on Oxygen Induced Retinal Vasoconstriction in LPS Induced Inflammatory Model in Humans

Healthy Subjects Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02221089
• Other study ID #: OPHT-090911
• Status: Completed
• Phase: N/A
• First received: January 31, 2013
• Last updated: August 18, 2014
• Start date: January 2013
• Est. completion date: July 2014

Study information

• Verified date: August 2014
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Ethikkommission
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: July 2014
• Est. primary completion date: December 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 35 Years

Eligibility

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, ametropy < 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy Subjects
• Imparied Retinal Vascular Reactivity

Intervention

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

Dietary Supplement:
• Retaron®
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

Other:
• Placebo
Placebo capsules identical in appearance to Retaron capsules

Locations

Country	Name	City	State
Austria	Department of clinical Pharmacology, Medical University of Vienna	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Vienna

Country where clinical trial is conducted

Austria, 

References & Publications (5)

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. Erratum in: Arch Ophthalmol. 2008 Sep;126(9):1251. — View Citation

Kolodjaschna J, Berisha F, Lasta M, Polska E, Fuchsjäger-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. — View Citation

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. Epub 2004 Mar 11. — View Citation

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. — View Citation

Violi F, Cangemi R. Antioxidants and cardiovascular disease. Curr Opin Investig Drugs. 2005 Sep;6(9):895-900. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	Change in impaired endothelial function	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	No
Secondary	Change in antioxidative capacity	To investigate the antioxidative capacity in the blood by determination of malondialdehyd (MDA) levels	Study day 1 and 2	No