Role of Nitric Oxide in Optic Nerve Head Blood Flow Regulation During Experimental Increase of Intraocular Pressure in Healthy Humans

Autoregulation is defined as the ability of a vascular bed to adapt its vascular resistance to changes in perfusion pressure. In the eye, several studies have reported that retinal blood flow is autoregulated over a wide range of ocular perfusion pressures. Large scale studies have shown that reduced ocular perfusion pressure is an important risk factor for the prevalence, the incidence and the progression of primary open angle glaucoma.

Former studies that investigated ocular blood flow autoregulation focused mainly on choroidal blood flow. For the optic nerve head only few data are available, although it seems likely that it underlies similar autoregulatory mechanisms.

A previous study investigating choroidal blood flow has shown that nitric oxide (NO) plays a key role in choroidal autoregulation. The present study is designed to test the hypothesis that NO plays a role in optic nerve head autoregulation during increased intraocular pressure (IOP). Therefore, IOP will be experimentally increased using a suction cup device in the absence of presence of either a nitric oxide synthase inhibitor (L-NMMA), an α-receptor agonist (phenylephrine) or placebo. Optic nerve head blood flow will be continuously measured during the procedure.

Study Overview

• Status: Terminated
• Conditions: Healthy
• Intervention / Treatment: Device: Goldmann applanation tonometer; Drug: NG-monomethyl-L-arginine (L-NMMA); Drug: Physiological saline solution (as placebo); Drug: Phenylephrine; Device: Laser Doppler Flowmetry; Device: Suction cup

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Department of Clinical Pharmacology, Medical University of Vienna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women aged between 18 and 35 years, nonsmokers
• Men and women will be included in equal parts
• Normal findings in the medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant
• Normal findings in the laboratory testings unless the investigator considers an abnormality to be clinically irrelevant
• Normal ophthalmic findings, ametropia less than 1 diopter

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 (except intake of oral contraceptives)
• Symptoms of a clinically relevant illness in the 3 weeks before the first study day
• 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
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Phenylephrine	Device: Goldmann applanation tonometer; intraocular pressure measurements; Drug: NG-monomethyl-L-arginine (L-NMMA); bolus 6mg/kg over 5 minutes followed by a continuous infusion of 60µg/kg/min over 15 minutes; Drug: Physiological saline solution (as placebo); infusion period 20 minutes; Drug: Phenylephrine; 1µg/kg/min, infusion period 20 minutes; Device: Laser Doppler Flowmetry; Measurements will be performed at the neuroretinal rim to assess ONH blood flow.; Device: Suction cup; Experimental stepwise increase of intraocular pressure while measurement of optic nerve head blood flow.
Active Comparator: NG-monomethyl-L-arginine (L-NMMA)	Device: Goldmann applanation tonometer; intraocular pressure measurements; Drug: NG-monomethyl-L-arginine (L-NMMA); bolus 6mg/kg over 5 minutes followed by a continuous infusion of 60µg/kg/min over 15 minutes; Drug: Physiological saline solution (as placebo); infusion period 20 minutes; Drug: Phenylephrine; 1µg/kg/min, infusion period 20 minutes; Device: Laser Doppler Flowmetry; Measurements will be performed at the neuroretinal rim to assess ONH blood flow.; Device: Suction cup; Experimental stepwise increase of intraocular pressure while measurement of optic nerve head blood flow.
Placebo Comparator: Physiological saline solution	Device: Goldmann applanation tonometer; intraocular pressure measurements; Drug: NG-monomethyl-L-arginine (L-NMMA); bolus 6mg/kg over 5 minutes followed by a continuous infusion of 60µg/kg/min over 15 minutes; Drug: Physiological saline solution (as placebo); infusion period 20 minutes; Drug: Phenylephrine; 1µg/kg/min, infusion period 20 minutes; Device: Laser Doppler Flowmetry; Measurements will be performed at the neuroretinal rim to assess ONH blood flow.; Device: Suction cup; Experimental stepwise increase of intraocular pressure while measurement of optic nerve head blood flow.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
optic nerve head pressure-flow relationship	1 year

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Gabriele Fuchsjaeger-Mayrl, MD, Univ.Doz., Department of Clinical Pharmacology, Medical University of Vienna

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: June 1, 2009
• First Submitted That Met QC Criteria: June 4, 2009
• First Posted (Estimate): June 5, 2009

Study Record Updates

• Last Update Posted (Estimate): November 14, 2014
• Last Update Submitted That Met QC Criteria: November 13, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: Intraocular Pressure; Optic Disk; Regional Blood Flow; Ocular Physiology; L-NG-Monomethyl Arginine; Optic Nerve Head Blood Flow
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Protective Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Respiratory System Agents; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Nasal Decongestants; Adrenergic alpha-1 Receptor Agonists; Phenylephrine; Oxymetazoline; omega-N-Methylarginine
• Other Study ID Numbers: OPHT-310708