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Completed

NCT Number: NCT00431691

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.

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Key information

Age range

18 year–35 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 4

Primary location

Department of Clinical Pharmacology, Medical University of Vienna

Vienna, 1090, Austria

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Vitamin and mineral supplement

Drug

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: Ocuvite preservision

Escherichia coli Endotoxin (LPS)

Drug

dose: 2 ng/kg (corresponding to 20 IU/kg), intravenous bolus over 5 minutes on both study days

Other names: US Standard Endotoxin

100% O2

Drug

breathing for 30 minutes, 2 breathing periods on both study days

Nitroglycerin

Drug

dose: 0,8 mg sublingual, applied during FMD measurements on both study days

Other names: Nitrolingual Pump Spray

Primary outcomes

  1. Retinal blood flow

    Time frame: in total 8x on 2 study days

Secondary outcomes

  1. Choroidal blood flow

    Time frame: in total 4x on 2 study days

  2. Flow mediated dilation (FMD) of brachial artery assessed with ultrasound

    Time frame: in total 4x on 2 study days

  3. Blood pressure, heart rate

    Time frame: on 2 study days

  4. Body temperature

    Time frame: on 2 study days

  5. Concentration of cytokines in plasma

    Time frame: on 2 study days

Sponsors and collaborators

Lead sponsor

Medical University of Vienna

Other

Registry information

Important dates

Study start
2006
Primary completion
2007
Study completion
2007
First posted
Feb 6, 2007
Registry last updated
Jul 4, 2008

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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