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

Study Overview
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Brief Summary
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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.

Conditions
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Imparied Retinal Vascular Reactivity, Healthy Subjects

Intervention / Treatment
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* Drug: Escherichia coli Endotoxin
* Dietary Supplement: Retaron®
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Retaron<br> | Drug: Escherichia coli Endotoxin<br>* dose: 2 ng/kg bodyweight (corresponding to 20 IU/kg), i.v. bolus on both study days.<br>* Other names: LPS, US Standard Reference Endotoxin;Dietary Supplement: Retaron®<br>* 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<br>|
| Placebo Comparator: Placebo<br> | Drug: Escherichia coli Endotoxin<br>* dose: 2 ng/kg bodyweight (corresponding to 20 IU/kg), i.v. bolus on both study days.<br>* Other names: LPS, US Standard Reference Endotoxin;Other: Placebo<br>* Placebo capsules identical in appearance to Retaron capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Effect of Retaron on imparied retinal vascular reactivity after LPS administration in healthy subjects