Effect of Antioxidants on Ocular Blood Flow, Endothelial Function, and Cytokine Levels in LPS Induced Inflammatory Model in Humans.
1 other identifier
interventional
22
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_4
Started Sep 2006
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 1, 2006
CompletedFirst Submitted
Initial submission to the registry
February 5, 2007
CompletedFirst Posted
Study publicly available on registry
February 6, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2007
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2007
CompletedJuly 4, 2008
July 1, 2008
1.2 years
February 5, 2007
July 1, 2008
Conditions
Outcome Measures
Primary Outcomes (1)
Retinal blood flow
in total 8x on 2 study days
Secondary Outcomes (5)
Choroidal blood flow
in total 4x on 2 study days
Flow mediated dilation (FMD) of brachial artery assessed with ultrasound
in total 4x on 2 study days
Blood pressure, heart rate
on 2 study days
Body temperature
on 2 study days
Concentration of cytokines in plasma
on 2 study days
Study Arms (2)
1
ACTIVE COMPARATOR2
PLACEBO COMPARATORInterventions
dose: 4 tablets daily for two weeks vitamin A 7160 IU, vitamin C 113mg, vitamin E 100IU, zinc 17.4mg, copper 0.4mg
dose: 2 ng/kg (corresponding to 20 IU/kg), intravenous bolus over 5 minutes on both study days
dose: 0,8 mg sublingual, applied during FMD measurements on both study days
Eligibility Criteria
You may qualify if:
- 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
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, 1090, Austria
Related Publications (1)
Pemp B, Polska E, Karl K, Lasta M, Minichmayr A, Garhofer G, Wolzt M, Schmetterer L. Effects of antioxidants (AREDS medication) on ocular blood flow and endothelial function in an endotoxin-induced model of oxidative stress in humans. Invest Ophthalmol Vis Sci. 2010 Jan;51(1):2-6. doi: 10.1167/iovs.09-3888. Epub 2009 Aug 13.
PMID: 19684008DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Michael Wolzt, MD
Department of Clinical Pharmacology, Medical University of Vienna
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
Study Record Dates
First Submitted
February 5, 2007
First Posted
February 6, 2007
Study Start
September 1, 2006
Primary Completion
December 1, 2007
Study Completion
December 1, 2007
Last Updated
July 4, 2008
Record last verified: 2008-07