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

NCT ID: NCT00914394

Last Updated: 2014-11-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-10-31

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.

Detailed Description

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Conditions

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Healthy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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NG-monomethyl-L-arginine (L-NMMA)

Group Type ACTIVE_COMPARATOR

NG-monomethyl-L-arginine (L-NMMA)

Intervention Type DRUG

bolus 6mg/kg over 5 minutes followed by a continuous infusion of 60µg/kg/min over 15 minutes

Phenylephrine

Intervention Type DRUG

1µg/kg/min, infusion period 20 minutes

Physiological saline solution (as placebo)

Intervention Type DRUG

infusion period 20 minutes

Laser Doppler Flowmetry

Intervention Type DEVICE

Measurements will be performed at the neuroretinal rim to assess ONH blood flow.

Goldmann applanation tonometer

Intervention Type DEVICE

intraocular pressure measurements

Suction cup

Intervention Type DEVICE

Experimental stepwise increase of intraocular pressure while measurement of optic nerve head blood flow.

Phenylephrine

Group Type ACTIVE_COMPARATOR

NG-monomethyl-L-arginine (L-NMMA)

Intervention Type DRUG

bolus 6mg/kg over 5 minutes followed by a continuous infusion of 60µg/kg/min over 15 minutes

Phenylephrine

Intervention Type DRUG

1µg/kg/min, infusion period 20 minutes

Physiological saline solution (as placebo)

Intervention Type DRUG

infusion period 20 minutes

Laser Doppler Flowmetry

Intervention Type DEVICE

Measurements will be performed at the neuroretinal rim to assess ONH blood flow.

Goldmann applanation tonometer

Intervention Type DEVICE

intraocular pressure measurements

Suction cup

Intervention Type DEVICE

Experimental stepwise increase of intraocular pressure while measurement of optic nerve head blood flow.

Physiological saline solution

Group Type PLACEBO_COMPARATOR

NG-monomethyl-L-arginine (L-NMMA)

Intervention Type DRUG

bolus 6mg/kg over 5 minutes followed by a continuous infusion of 60µg/kg/min over 15 minutes

Phenylephrine

Intervention Type DRUG

1µg/kg/min, infusion period 20 minutes

Physiological saline solution (as placebo)

Intervention Type DRUG

infusion period 20 minutes

Laser Doppler Flowmetry

Intervention Type DEVICE

Measurements will be performed at the neuroretinal rim to assess ONH blood flow.

Goldmann applanation tonometer

Intervention Type DEVICE

intraocular pressure measurements

Suction cup

Intervention Type DEVICE

Experimental stepwise increase of intraocular pressure while measurement of optic nerve head blood flow.

Interventions

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NG-monomethyl-L-arginine (L-NMMA)

bolus 6mg/kg over 5 minutes followed by a continuous infusion of 60µg/kg/min over 15 minutes

Intervention Type DRUG

Phenylephrine

1µg/kg/min, infusion period 20 minutes

Intervention Type DRUG

Physiological saline solution (as placebo)

infusion period 20 minutes

Intervention Type DRUG

Laser Doppler Flowmetry

Measurements will be performed at the neuroretinal rim to assess ONH blood flow.

Intervention Type DEVICE

Goldmann applanation tonometer

intraocular pressure measurements

Intervention Type DEVICE

Suction cup

Experimental stepwise increase of intraocular pressure while measurement of optic nerve head blood flow.

Intervention Type DEVICE

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

35 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Medical University of Vienna

OTHER

Sponsor Role lead

Responsible Party

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Gerhard Garhofer

Assoc Prof Priv-Doz Dr

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Gabriele Fuchsjaeger-Mayrl, MD, Univ.Doz.

Role: PRINCIPAL_INVESTIGATOR

Department of Clinical Pharmacology, Medical University of Vienna

Locations

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Department of Clinical Pharmacology, Medical University of Vienna

Vienna, Vienna, Austria

Site Status

Countries

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Austria

Other Identifiers

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OPHT-310708

Identifier Type: -

Identifier Source: org_study_id