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

This study has been completed.
Sponsor:
Information provided by:
Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT00431691
First received: February 5, 2007
Last updated: July 1, 2008
Last verified: July 2008
  Purpose

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.


Condition Intervention Phase
Retina
Regional Blood Flow
Endotoxin, Escherichia Coli
Drug: vitamin and mineral supplement
Drug: Escherichia coli Endotoxin (LPS)
Drug: 100% O2
Drug: nitroglycerin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Effect of Antioxidants on Ocular Blood Flow, Endothelial Function, and Cytokine Levels in LPS Induced Inflammatory Model in Humans.

Resource links provided by NLM:


Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:
  • Retinal blood flow [ Time Frame: in total 8x on 2 study days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Choroidal blood flow [ Time Frame: in total 4x on 2 study days ] [ Designated as safety issue: No ]
  • Flow mediated dilation (FMD) of brachial artery assessed with ultrasound [ Time Frame: in total 4x on 2 study days ] [ Designated as safety issue: No ]
  • Blood pressure, heart rate [ Time Frame: on 2 study days ] [ Designated as safety issue: Yes ]
  • Body temperature [ Time Frame: on 2 study days ] [ Designated as safety issue: Yes ]
  • Concentration of cytokines in plasma [ Time Frame: on 2 study days ] [ Designated as safety issue: No ]

Enrollment: 22
Study Start Date: September 2006
Study Completion Date: December 2007
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1 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

Other Name: Ocuvite preservision
Drug: Escherichia coli Endotoxin (LPS)
dose: 2 ng/kg (corresponding to 20 IU/kg), intravenous bolus over 5 minutes on both study days
Other Name: US Standard Endotoxin
Drug: 100% O2
breathing for 30 minutes, 2 breathing periods on both study days
Drug: nitroglycerin
dose: 0,8 mg sublingual, applied during FMD measurements on both study days
Other Name: Nitrolingual Pump Spray
Placebo Comparator: 2 Drug: Escherichia coli Endotoxin (LPS)
dose: 2 ng/kg (corresponding to 20 IU/kg), intravenous bolus over 5 minutes on both study days
Other Name: US Standard Endotoxin
Drug: 100% O2
breathing for 30 minutes, 2 breathing periods on both study days
Drug: nitroglycerin
dose: 0,8 mg sublingual, applied during FMD measurements on both study days
Other Name: Nitrolingual Pump Spray

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00431691

Locations
Austria
Department of Clinical Pharmacology, Medical University of Vienna
Vienna, Austria, 1090
Sponsors and Collaborators
Medical University of Vienna
Investigators
Principal Investigator: Michael Wolzt, MD Department of Clinical Pharmacology, Medical University of Vienna
  More Information

No publications provided by Medical University of Vienna

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Michael Wolzt, MD, Department of Clinical Pharmacology, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT00431691     History of Changes
Other Study ID Numbers: OPHT-110106
Study First Received: February 5, 2007
Last Updated: July 1, 2008
Health Authority: Austria: Agency for Health and Food Safety

Additional relevant MeSH terms:
Antioxidants
Nitroglycerin
Vitamins
Cardiovascular Agents
Growth Substances
Micronutrients
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on October 30, 2014