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

Study Overview
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Brief Summary
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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.

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

Conditions
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Healthy

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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L-NG-Monomethyl Arginine, Optic Nerve Head Blood Flow, Intraocular Pressure, Regional Blood Flow, Ocular Physiology, Optic Disk