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

NCT ID: NCT00406731

Last Updated: 2019-08-15

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2014-11-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Interventions

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

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

Intervention Type: DRUG

Endothelin-1 (ET-1)

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

Intervention Type: DRUG

Physiologic saline solution (placebo control)

intravenous infusion over 20 minutes; twice on 1 study day

Intervention Type: DRUG

Laser Doppler flowmetry

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

Intervention Type: DEVICE

Goldmann applanation tonometer

Intraocular pressure measurements

Intervention Type: DEVICE

HP-CMS patient monitor

blood pressure and pulse rate measurements

Intervention Type: DEVICE

Suction cup method

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.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• 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

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 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Gerhard Garhofer

Assoc. Prof. PD Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gabriele Fuchsjaeger-Mayrl, MD,Univ.Doz.

Role: PRINCIPAL_INVESTIGATOR

Department of Clinical Pharmacology, Medical University of Vienna

Locations

Department of Clinical Pharmacology, Medical University of Vienna

Vienna, , Austria

Countries

Austria

Other Identifiers

OPHT-080206

Identifier Type: -

Identifier Source: org_study_id