<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02221089</url>
  </required_header>
  <id_info>
    <org_study_id>OPHT-090911</org_study_id>
    <nct_id>NCT02221089</nct_id>
  </id_info>
  <brief_title>Effect of Retaron® on Oxygen Induced Retinal Vasoconstriction in LPS Induced Inflammatory Model in Humans</brief_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Vienna</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of Vienna</source>
  <brief_summary>
    <textblock>
      Oxidative stress has been implicated to play a pathogenic role in many disease processes,&#xD;
      especially in age-related disorders such as age-related macular degeneration. It has been&#xD;
      hypothesized that antioxidative agents such as vitamins and minerals, which are capable of&#xD;
      scavenging free radicals, may reduce oxidative stress and may, in turn, be beneficial for&#xD;
      patients with age-related disorders. Based on this hypothesis several different combinations&#xD;
      of vitamins have been introduced, all targeting at reducing oxidative stress. However, the&#xD;
      in-vivo effect of the antioxidative properties of a certain drug or vitamin combination is&#xD;
      hard to investigate. In the current study, we propose to investigate the effect of Retaron®,&#xD;
      a combination of carotoinoids, omega-3-fatty acids, a herbal extract of Aronia, vitamins and&#xD;
      trace elements, in a systemic in-vivo inflammation model.&#xD;
&#xD;
      In the present study, the infusion of LPS, which is a cell wall component of gram-negative&#xD;
      bacteria and a major mediator in the pathogenesis of septic shock, will be used as a&#xD;
      standardized experimental model of systemic inflammation in humans. Given that inflammation&#xD;
      is associated with enhanced oxidative stress and widespread endothelial dysfunction, the LPS&#xD;
      model is well suitable for determination of the antioxidative effects of Retaron®. As a main&#xD;
      outcome parameter the vascular reactivity of retinal vessels to systemic hyperoxia (induced&#xD;
      by breathing 100% oxygen) will be tested in presence or absence of the antioxidant&#xD;
      combination.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 2013</start_date>
  <completion_date type="Actual">July 2014</completion_date>
  <primary_completion_date type="Actual">December 2013</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Retinal Vascular Reactivity</measure>
    <time_frame>Study day 1 and 2</time_frame>
    <description>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).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Ocular blood flow</measure>
    <time_frame>Study day 1 and 2</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in impaired endothelial function</measure>
    <time_frame>Study day 1 and 2</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in antioxidative capacity</measure>
    <time_frame>Study day 1 and 2</time_frame>
    <description>To investigate the antioxidative capacity in the blood by determination of malondialdehyd (MDA) levels</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Imparied Retinal Vascular Reactivity</condition>
  <condition>Healthy Subjects</condition>
  <arm_group>
    <arm_group_label>Retaron</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Escherichia coli Endotoxin</intervention_name>
    <description>dose: 2 ng/kg bodyweight (corresponding to 20 IU/kg), i.v. bolus on both study days.</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Retaron</arm_group_label>
    <other_name>LPS, US Standard Reference Endotoxin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Retaron®</intervention_name>
    <description>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</description>
    <arm_group_label>Retaron</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo capsules identical in appearance to Retaron capsules</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men aged between 18 and 35 years, nonsmokers&#xD;
&#xD;
          -  Body mass index between 15th and 85th percentile (Must et al. 1991)&#xD;
&#xD;
          -  Normal findings in the medical history and physical examination unless the&#xD;
             investigator considers an abnormality to be clinically irrelevant&#xD;
&#xD;
          -  Normal laboratory values unless the investigator considers an abnormality to be&#xD;
             clinically irrelevant&#xD;
&#xD;
          -  Normal ophthalmic findings, ametropy &lt; 3 Dpt.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Regular use of medication, abuse of alcoholic beverages, participation in a clinical&#xD;
             trial in the 3 weeks preceding the study&#xD;
&#xD;
          -  Treatment in the previous 3 weeks with any drug, vitamins and minerals supplements as&#xD;
             well&#xD;
&#xD;
          -  Symptoms of a clinically relevant illness in the 3 weeks before the first study day&#xD;
&#xD;
          -  History of hypersensitivity to the trial drug or to drugs with a similar chemical&#xD;
             structure&#xD;
&#xD;
          -  History or presence of gastrointestinal, liver or kidney disease, or other conditions&#xD;
             known to interfere with distribution, metabolism or excretion of study drugs&#xD;
&#xD;
          -  Blood donation during the previous 3 weeks&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Department of clinical Pharmacology, Medical University of Vienna</name>
      <address>
        <city>Vienna</city>
        <zip>1080</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <reference>
    <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. doi: 10.1152/ajpheart.01240.2003. Epub 2004 Mar 11.</citation>
    <PMID>15016626</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>18614167</PMID>
  </reference>
  <reference>
    <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. doi: 10.1086/314717.</citation>
    <PMID>10191237</PMID>
  </reference>
  <reference>
    <citation>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. Erratum In: Arch Ophthalmol. 2008 Sep;126(9):1251.</citation>
    <PMID>11594942</PMID>
  </reference>
  <reference>
    <citation>Violi F, Cangemi R. Antioxidants and cardiovascular disease. Curr Opin Investig Drugs. 2005 Sep;6(9):895-900.</citation>
    <PMID>16187689</PMID>
  </reference>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>January 31, 2013</study_first_submitted>
  <study_first_submitted_qc>August 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2014</study_first_posted>
  <last_update_submitted>August 18, 2014</last_update_submitted>
  <last_update_submitted_qc>August 18, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 20, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of Vienna</investigator_affiliation>
    <investigator_full_name>Gerhard Garhofer</investigator_full_name>
    <investigator_title>assoc. Prof. Dr.med.univ.</investigator_title>
  </responsible_party>
  <keyword>Effect of Retaron on imparied retinal vascular reactivity after LPS administration in healthy subjects</keyword>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02221089
org study id: OPHT-090911
nct id: NCT02221089
lead sponsor: 
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Change in Retinal Vascular Reactivity
time frame: Study day 1 and 2
description: 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).
measure: Change in Ocular blood flow
time frame: Study day 1 and 2
description: 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.
measure: Change in impaired endothelial function
time frame: Study day 1 and 2
description: 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.
measure: Change in antioxidative capacity
time frame: Study day 1 and 2
description: To investigate the antioxidative capacity in the blood by determination of malondialdehyd (MDA) levels
arm group label: Retaron
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Escherichia coli Endotoxin
description: dose: 2 ng/kg bodyweight (corresponding to 20 IU/kg), i.v. bolus on both study days.
arm group label: Placebo
arm group label: Retaron
other name: LPS, US Standard Reference Endotoxin
intervention type: Dietary Supplement
intervention name: Retaron®
description: 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
arm group label: Retaron
intervention type: Other
intervention name: Placebo
description: Placebo capsules identical in appearance to Retaron capsules
arm group label: Placebo
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 35 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Austria
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. doi: 10.1152/ajpheart.01240.2003. Epub 2004 Mar 11.
PMID: 15016626
citation: 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: 18614167
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. doi: 10.1086/314717.
PMID: 10191237
citation: 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. Erratum In: Arch Ophthalmol. 2008 Sep;126(9):1251.
PMID: 11594942
citation: Violi F, Cangemi R. Antioxidants and cardiovascular disease. Curr Opin Investig Drugs. 2005 Sep;6(9):895-900.
PMID: 16187689
responsible party type: Principal Investigator
investigator affiliation: Medical University of Vienna
investigator full name: Gerhard Garhofer
investigator title: assoc. Prof. Dr.med.univ.