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
Conditions
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Vienna, Austria, 1090
- Department of Clinical Pharmacology, Medical University of Vienna
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Active Comparator: Phenylephrine
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intraocular pressure measurements
bolus 6mg/kg over 5 minutes followed by a continuous infusion of 60µg/kg/min over 15 minutes
infusion period 20 minutes
1µg/kg/min, infusion period 20 minutes
Measurements will be performed at the neuroretinal rim to assess ONH blood flow.
Experimental stepwise increase of intraocular pressure while measurement of optic nerve head blood flow.
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Active Comparator: NG-monomethyl-L-arginine (L-NMMA)
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intraocular pressure measurements
bolus 6mg/kg over 5 minutes followed by a continuous infusion of 60µg/kg/min over 15 minutes
infusion period 20 minutes
1µg/kg/min, infusion period 20 minutes
Measurements will be performed at the neuroretinal rim to assess ONH blood flow.
Experimental stepwise increase of intraocular pressure while measurement of optic nerve head blood flow.
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Placebo Comparator: Physiological saline solution
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intraocular pressure measurements
bolus 6mg/kg over 5 minutes followed by a continuous infusion of 60µg/kg/min over 15 minutes
infusion period 20 minutes
1µg/kg/min, infusion period 20 minutes
Measurements will be performed at the neuroretinal rim to assess ONH blood flow.
Experimental stepwise increase of intraocular pressure while measurement of optic nerve head blood flow.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
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optic nerve head pressure-flow relationship
Time Frame: 1 year
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1 year
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Collaborators and Investigators
Sponsor
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
Primary Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
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
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