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

Purpose

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.

Condition	Intervention
Healthy	Drug: NG-monomethyl-L-arginine (L-NMMA) Drug: Phenylephrine Drug: Physiological saline solution (as placebo) Device: Laser Doppler Flowmetry Device: Goldmann applanation tonometer Device: Suction cup

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Basic Science
Official Title:	Role of Nitric Oxide in Optic Nerve Head Blood Flow Regulation During Experimental Increase of Intraocular Pressure in Healthy Humans

Resource links provided by NLM:

Drug Information available for: Phenylephrine Phenylephrine hydrochloride Arginine Arginine Hydrochloride Oxymetazoline Oxymetazoline hydrochloride Nitric oxide

U.S. FDA Resources

Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:

optic nerve head pressure-flow relationship [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment:	24
Study Start Date:	July 2009
Estimated Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: NG-monomethyl-L-arginine (L-NMMA)	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: Phenylephrine 1µg/kg/min, infusion period 20 minutes Drug: Physiological saline solution (as placebo) infusion period 20 minutes Device: Laser Doppler Flowmetry Measurements will be performed at the neuroretinal rim to assess ONH blood flow. Device: Goldmann applanation tonometer intraocular pressure measurements Device: Suction cup Experimental stepwise increase of intraocular pressure while measurement of optic nerve head blood flow.
Active Comparator: Phenylephrine	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: Phenylephrine 1µg/kg/min, infusion period 20 minutes Drug: Physiological saline solution (as placebo) infusion period 20 minutes Device: Laser Doppler Flowmetry Measurements will be performed at the neuroretinal rim to assess ONH blood flow. Device: Goldmann applanation tonometer intraocular pressure measurements Device: Suction cup Experimental stepwise increase of intraocular pressure while measurement of optic nerve head blood flow.
Placebo Comparator: Physiological saline solution	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: Phenylephrine 1µg/kg/min, infusion period 20 minutes Drug: Physiological saline solution (as placebo) infusion period 20 minutes Device: Laser Doppler Flowmetry Measurements will be performed at the neuroretinal rim to assess ONH blood flow. Device: Goldmann applanation tonometer intraocular pressure measurements Device: Suction cup Experimental stepwise increase of intraocular pressure while measurement of optic nerve head blood flow.

Eligibility

Ages Eligible for Study:	18 Years to 35 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00914394

Contacts

Contact: Gerhard Garhoefer, MD, Priv-Doz

0043 1 40400 ext 2981

gerhard.garhoefer@meduniwien.ac.at

Locations

Austria
Department of Clinical Pharmacology, Medical University of Vienna	Not yet recruiting
Vienna, Austria, 1090
Contact: Gerhard Garhoefer, MD, Priv.-Doz. 0043 1 40400 ext 2981 gerhard.garhoefer@meduniwien.ac.at

Sponsors and Collaborators

Medical University of Vienna

Investigators

Principal Investigator:

Gabriele Fuchsjaeger-Mayrl, MD, Univ.Doz.

Department of Clinical Pharmacology, Medical University of Vienna

More Information

No publications provided

Responsible Party:	Gabriele Fuchsjaeger-Mayrl, MD, Department of Clinical Pharmacology, Medical University of Vienna
ClinicalTrials.gov Identifier:	NCT00914394 History of Changes
Other Study ID Numbers:	OPHT-310708
Study First Received:	June 1, 2009
Last Updated:	June 4, 2009
Health Authority:	Austria: Agency for Health and Food Safety

Keywords provided by Medical University of Vienna:

L-NG-Monomethyl Arginine
Optic Nerve Head Blood Flow
Intraocular Pressure

Regional Blood Flow
Ocular Physiology
Optic Disk

Additional relevant MeSH terms:

Nitric Oxide
Phenylephrine
Oxymetazoline
Omega-N-Methylarginine
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action

Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Cardiovascular Agents
Protective Agents
Adrenergic alpha-1 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Cardiotonic Agents
Mydriatics
Sympathomimetics
Vasoconstrictor Agents
Nasal Decongestants
Enzyme Inhibitors

ClinicalTrials.gov processed this record on May 19, 2013