Role of Endothelin- and Nitric Oxide-system in the Regulation of Optic Nerve Head Blood Flow During Changes in Ocular Perfusion Pressure

NCT00406731 | Withdrawn Phase 2 DMC

• 1 other identifier: OPHT-080206
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Autoregulation is the ability of a vascular bed to maintain blood flow despite changes in perfusion pressure. The existence of an effective autoregulation in the optic nerve circulation has been shown in animals and humans. The exact mechanism behind this autoregulation is still unknown. The motive for the investigation of optic nerve head (ONH) blood flow autoregulation is to enhance the understanding of pathologic eye conditions associated with ocular vascular disorders. To clarify the regulatory mechanisms of ONH microcirculation is of critical importance to understand the pathophysiology of glaucoma because there is evidence that glaucoma is associated with optic nerve head ischemia. Several studies indicate that a disturbed autoregulation might contribute to glaucomatous optic neuropathy. Previous findings suggest endothelial dysfunction in glaucomatous optic neuropathy, in particular alterations in endothelin- and nitric oxide- system, which both play an important role in local regulation of vascular tone. In the present study, changes in ocular perfusion pressure will be performed during administration of drugs, which may potentially alter the pressure-flow relationship. These drugs include endothelin-1 and the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA).

Conditions

Ocular Physiology; Optic Disk; Regional Blood Flow

Keywords

Endothelin-1; L-NG-Monomethyl Arginine; Optic Nerve Head blood flow

Outcome Measures

Primary Outcomes (1)

• ONH pressure-flow relationship

  up to 3 study days

Interventions

NG-monomethyl-L-arginine (L-NMMA) DRUG

bolus 6 mg/kg over 5 minutes followed by a continuous intravenous infusion of 60 µg/kg/min over 12 minutes; twice on 1 study day

Endothelin-1 (ET-1) DRUG

5 ng/kg/min intravenous infusion over 17 minutes; twice on 1 study day

Physiologic saline solution (placebo control) DRUG

intravenous infusion over 20 minutes; twice on 1 study day

Laser Doppler flowmetry DEVICE

blood flow measurements at the temporal neuroretinal rim of the optic nerve head

Goldmann applanation tonometer DEVICE

Intraocular pressure measurements

HP-CMS patient monitor DEVICE

blood pressure and pulse rate measurements

Suction cup method PROCEDURE

The IOP will be raised by an 11 mm diameter, standardized suction cup placed on the temporal sclera with the anterior edge at least 1 mm from the limbus.

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Men aged between 18 and 35 years, nonsmokers
• Body mass index between 15th and 85th percentile (Must et al. 1991)
• 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, ametropy \< 1 Dpt

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 systemic or pulmonary hypertension, or other cardiac or pulmonary diseases
• 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, Medical University of Vienna

Vienna, 1090, Austria

Location

MeSH Terms

Interventions

omega-N-Methylarginine; Endothelin-1; Laser-Doppler Flowmetry

Intervention Hierarchy (Ancestors)

Arginine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential; Endothelins; Intercellular Signaling Peptides and Proteins; Peptides; Proteins; Biological Factors; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Rheology; Investigative Techniques

Study Officials

• Gabriele Fuchsjaeger-Mayrl, MD,Univ.Doz.

  Department of Clinical Pharmacology, Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assoc. Prof. PD Dr.

Study Record Dates

• First Submitted: November 30, 2006
• First Posted: December 4, 2006
• Study Start: January 1, 2008
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: August 15, 2019

Record last verified: 2019-08

Locations

AU (1)