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

NCT00708357 | Terminated Early Phase 1

• 1 other identifier: OPHT-311004
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Ocular Physiology; Regional Blood Flow

Keywords

eNOS Gene Polymorphism; ocular blood flow

Outcome Measures

Primary Outcomes (1)

• Genotyping

  performed during the first year before measurements

Study Arms (2)

1

OTHER

homozygous mutant: CC allele of the eNOS T-786C gene

Drug: NG-monomethyl-L-arginine

2

OTHER

homozygous mutant: TT allele of the eNOS T-786C gene

Drug: NG-monomethyl-L-arginine

Interventions

NG-monomethyl-L-arginine DRUG

intravenous administration, bolus over 5 minutes, dosage 6mg/kg

Also known as: L-NMMA

1; 2

Eligibility Criteria

• Age: 19 Years+
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Department of Clinical Pharmacology

Vienna, Austria

Location

MeSH Terms

Interventions

omega-N-Methylarginine

Intervention Hierarchy (Ancestors)

Arginine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential

Study Officials

• Michael Wolzt, MD

  Department of CLinical Pharmacology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assoc Prof Priv.-Doz. Dr

Study Record Dates

• First Submitted: June 26, 2008
• First Posted: July 2, 2008
• Study Start: May 1, 2005
• Primary Completion: December 1, 2009
• Study Completion: January 1, 2013
• Last Updated: November 17, 2014

Record last verified: 2014-11

Locations

AU (1)