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

Regional Blood Flow Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00406731
• Other study ID #: OPHT-080206
• Status: Withdrawn
• Phase: Phase 2
• Start date: January 2008
• Est. completion date: November 2014

Study information

• Verified date: August 2019
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 35 Years

Eligibility

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

Related Conditions & MeSH terms

• Ocular Physiology
• Optic Disk
• Regional Blood Flow

Intervention

Drug:
• 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
• Endothelin-1 (ET-1)
5 ng/kg/min intravenous infusion over 17 minutes; twice on 1 study day
• Physiologic saline solution (placebo control)
intravenous infusion over 20 minutes; twice on 1 study day

Device:
• Laser Doppler flowmetry
blood flow measurements at the temporal neuroretinal rim of the optic nerve head
• Goldmann applanation tonometer
Intraocular pressure measurements
• HP-CMS patient monitor
blood pressure and pulse rate measurements

Procedure:
• 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.

Locations

Country	Name	City	State
Austria	Department of Clinical Pharmacology, Medical University of Vienna	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Vienna

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ONH pressure-flow relationship		up to 3 study days