Does eNOS Gene Polymorphism Play a Role in the Maintenance of Basal Vascular Tone in the Choroid or Optic Nerve Head?

Nitric oxide (NO) is a potent endothelium-derived vasodilatator that plays a major role in the control of ocular blood flow. Endothelial NO synthase (eNOS) is one of three isoforms of NOS producing NO through hydroxylation of L-arginine. The eNOS gene is located on the long arm of chromosome 7, and different polymorphic variations have been identified. These single nucleotide polymorphisms (sNP´s) have the ability to change transcription activity and therefore enzyme levels. Recent data indicate that the T -786C polymorphism (especially the homozygous variant) is associated with reduced eNOS activity and consequently impaired NO production.

In the present study the investigators want to investigate if the T -786C eNOS gene polymorphism determines choroidal and optic nerve head blood flow.

Study Overview

• Status: Terminated
• Conditions: Ocular Physiology; Regional Blood Flow
• Intervention / Treatment: Drug: NG-monomethyl-L-arginine

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria
    • Department of Clinical Pharmacology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Men aged between 19 and 35 years, nonsmokers
• Normal findings in the medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant
• Homozygous variants of the T -786C genotyping (CC or TT)
• Normal ophthalmic findings, ametropia less than 3 diopters

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
• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 1; homozygous mutant: CC allele of the eNOS T-786C gene	Drug: NG-monomethyl-L-arginine; intravenous administration, bolus over 5 minutes, dosage 6mg/kg; Other Names: L-NMMA
Other: 2; homozygous mutant: TT allele of the eNOS T-786C gene	Drug: NG-monomethyl-L-arginine; intravenous administration, bolus over 5 minutes, dosage 6mg/kg; Other Names: L-NMMA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Genotyping	performed during the first year before measurements

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Michael Wolzt, MD, Department of Clinical Pharmacology

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: June 26, 2008
• First Submitted That Met QC Criteria: June 30, 2008
• First Posted (Estimate): July 2, 2008

Study Record Updates

• Last Update Posted (Estimate): November 17, 2014
• Last Update Submitted That Met QC Criteria: November 14, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: ocular blood flow; eNOS Gene Polymorphism
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; omega-N-Methylarginine
• Other Study ID Numbers: OPHT-311004