NCT02221089

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Jan 2013

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2013

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

January 31, 2013

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2013

Completed
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2014

Completed
2 months until next milestone

First Posted

Study publicly available on registry

August 20, 2014

Completed
Last Updated

August 20, 2014

Status Verified

August 1, 2014

Enrollment Period

11 months

First QC Date

January 31, 2013

Last Update Submit

August 18, 2014

Conditions

Imparied Retinal Vascular ReactivityHealthy Subjects

Keywords

Effect of Retaron on imparied retinal vascular reactivity after LPS administration in healthy subjects

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (3)

  • Change in Ocular blood flow

    Study day 1 and 2

  • Change in impaired endothelial function

    Study day 1 and 2

  • Change in antioxidative capacity

    Study day 1 and 2

Study Arms (2)

Retaron

EXPERIMENTAL
Drug: Escherichia coli EndotoxinDietary Supplement: Retaron®

Placebo

PLACEBO COMPARATOR
Drug: Escherichia coli EndotoxinOther: Placebo

Interventions

Escherichia coli EndotoxinDRUG

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

Also known as: LPS, US Standard Reference Endotoxin
PlaceboRetaron
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

Retaron
PlaceboOTHER

Placebo capsules identical in appearance to Retaron capsules

Placebo

Eligibility Criteria

Age18 Years - 35 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (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, ametropy \< 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Department of clinical Pharmacology, Medical University of Vienna

Vienna, Vienna, 1080, Austria

Location

Related Publications (5)

  • 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.

    PMID: 15016626BACKGROUND

  • 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.

    PMID: 18614167BACKGROUND

  • 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.

    PMID: 10191237BACKGROUND

  • 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.

    PMID: 11594942BACKGROUND

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

    PMID: 16187689BACKGROUND

MeSH Terms

Interventions

endotoxin, Escherichia coliLipopolysaccharides

Intervention Hierarchy (Ancestors)

GlycoconjugatesCarbohydratesPolysaccharides, BacterialPolysaccharidesLipidsAntigens, BacterialAntigensBiological FactorsEndotoxinsBacterial ToxinsToxins, Biological

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
assoc. Prof. Dr.med.univ.

Study Record Dates

First Submitted

January 31, 2013

First Posted

August 20, 2014

Study Start

January 1, 2013

Primary Completion

December 1, 2013

Study Completion

July 1, 2014

Last Updated

August 20, 2014

Record last verified: 2014-08

Locations

AU(1)