Clinical trial NCT00431691: Effect of Antioxidants on Ocular Blood Flow, Endothelial Function, and Cytokine Levels in LPS Induced Inflammatory Model in Humans.
Official title: Effect of Antioxidants on Ocular Blood Flow, Endothelial Function, and Cytokine Levels in LPS Induced Inflammatory Model in Humans.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Retina
Regional Blood Flow
Endotoxin, Escherichia Coli
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2007-02-06
Enrollment: 22
Sex: MALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Retinal blood flow
timeFrame: in total 8x on 2 study days
Secondary outcomes:
measure: Choroidal blood flow
timeFrame: in total 4x on 2 study days
measure: Flow mediated dilation (FMD) of brachial artery assessed with ultrasound
timeFrame: in total 4x on 2 study days
measure: Blood pressure, heart rate
timeFrame: on 2 study days
measure: Body temperature
timeFrame: on 2 study days
measure: Concentration of cytokines in plasma
timeFrame: on 2 study days
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Department of Clinical Pharmacology, Medical University of Vienna
Study officials:
affiliation: Department of Clinical Pharmacology, Medical University of Vienna
name: Michael Wolzt, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.