Effect of Antioxidants on Ocular Blood Flow, Endothelial Function, and Cytokine Levels in LPS Induced Inflammatory Model in Humans.

Regional Blood Flow Clinical Trial

Official title:

Effect of Antioxidants on Ocular Blood Flow, Endothelial Function, and Cytokine Levels in LPS Induced Inflammatory Model in Humans.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00431691
• Other study ID #: OPHT-110106
• Status: Completed
• Phase: Phase 4
• First received: February 5, 2007
• Last updated: July 1, 2008
• Start date: September 2006
• Est. completion date: December 2007

Study information

• Verified date: July 2008
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Agency for Health and Food Safety
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: December 2007
• Est. primary completion date: December 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 35 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Endotoxin, Escherichia Coli
• Regional Blood Flow
• Retina

Intervention

Drug:
• vitamin and mineral supplement
dose: 4 tablets daily for two weeks vitamin A 7160 IU, vitamin C 113mg, vitamin E 100IU, zinc 17.4mg, copper 0.4mg
• Escherichia coli Endotoxin (LPS)
dose: 2 ng/kg (corresponding to 20 IU/kg), intravenous bolus over 5 minutes on both study days
• 100% O2
breathing for 30 minutes, 2 breathing periods on both study days
• nitroglycerin
dose: 0,8 mg sublingual, applied during FMD measurements on both study days

Locations

Country	Name	City	State
Austria	Department of Clinical Pharmacology, Medical University of Vienna	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Vienna

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Retinal blood flow		in total 8x on 2 study days	No
Secondary	Choroidal blood flow		in total 4x on 2 study days	No
Secondary	Flow mediated dilation (FMD) of brachial artery assessed with ultrasound		in total 4x on 2 study days	No
Secondary	Blood pressure, heart rate		on 2 study days	Yes
Secondary	Body temperature		on 2 study days	Yes
Secondary	Concentration of cytokines in plasma		on 2 study days	No