Effect of Antioxidants on Ocular Blood Flow, Endothelial Function, and Cytokine Levels in LPS Induced Inflammatory Model in Humans.
Oxidative stress, which refers to cellular damage caused by reactive oxygen intermediates, has been implicated in many disease processes, especially age-related disorders. Many trials investigating use of antioxidants in protecting different tissues against oxidative stress have been conducted, but the results are ambiguous.
Inflammation is generally associated with enhanced oxidative stress and widespread endothelial dysfunction. 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 inflammatory response in humans. The assessment of outcome parameters will include measurements of ocular blood flow, forearm blood flow and plasma concentration of cytokines. Measurements of ocular hemodynamics provide an unique chance to investigate local blood flow in humans non-invasively. Moreover, the retina is especially susceptible to oxidative stress because of its high consumption of oxygen, its high polyunsaturated fatty acid content, and its exposure to visible light. Evidence from literature clearly supports a role for oxidative stress in pathophysiology of several ocular diseases including diabetic retinopathy and age-related macular degeneration. To investigate the retinal vascular reactivity we will use systemic hyperoxia as a stimulus. The measurement of forearm blood flow will be use to assess endothelial function. The main study objective is to investigate the effect of oral vitamins and minerals supplementation on impaired retinal vascular reactivity after LPS administration.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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Vienna, Austria, 1090
- Department of Clinical Pharmacology, Medical University of Vienna
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Men aged between 18 and 35 years, nonsmokers
- Body mass index between 15th and 85th percentile
- 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, ametropia < 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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Placebo Comparator: 2
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dose: 2 ng/kg (corresponding to 20 IU/kg), intravenous bolus over 5 minutes on both study days
Other Names:
breathing for 30 minutes, 2 breathing periods on both study days
dose: 0,8 mg sublingual, applied during FMD measurements on both study days
Other Names:
|
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Active Comparator: 1
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dose: 4 tablets daily for two weeks vitamin A 7160 IU, vitamin C 113mg, vitamin E 100IU, zinc 17.4mg, copper 0.4mg
Other Names:
dose: 2 ng/kg (corresponding to 20 IU/kg), intravenous bolus over 5 minutes on both study days
Other Names:
breathing for 30 minutes, 2 breathing periods on both study days
dose: 0,8 mg sublingual, applied during FMD measurements on both study days
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Retinal blood flow
Time Frame: in total 8x on 2 study days
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in total 8x on 2 study days
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
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Choroidal blood flow
Time Frame: in total 4x on 2 study days
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in total 4x on 2 study days
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Flow mediated dilation (FMD) of brachial artery assessed with ultrasound
Time Frame: in total 4x on 2 study days
|
in total 4x on 2 study days
|
|
Blood pressure, heart rate
Time Frame: on 2 study days
|
on 2 study days
|
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Body temperature
Time Frame: on 2 study days
|
on 2 study days
|
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Concentration of cytokines in plasma
Time Frame: on 2 study days
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on 2 study days
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- OPHT-110106
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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