Effects of Non-Specific Endothelin-A Receptor Blockade on Ocular Blood Flow in Patients With Glaucoma

Several lines of evidence suggest now that ocular perfusion abnormalities may contribute to the progression of glaucoma. It has been hypothesised that increased endothelin-1 plasma levels, as seen in patients with glaucoma, may be related to these alterations in ocular blood flow. We could show in recent experiments that administration of ET-1 decreases ocular blood flow, whereas blocking of the ET-A receptors do not affect basal vascular tone in healthy subjects. In the current study we set out to evaluate the effect Bosentan, a non-selective ETA-receptor antagonist in patients with open-angle glaucoma. This should allow us to test the hypothesis that administration of an ET-1 receptor antagonist increases ocular blood flow in patients with glaucoma.

Investigations will be done with a retinal vessel analyzer to determine retinal vessel cross-sectional diameters, with laser Doppler flowmetry and laser Doppler velocimetry to determine subfoveal macular blood flow and optic nerve head blood flow and with laser interferometric measurements to determine fundus pulsation amplitude in the macula. The intraocular pressure will be measured with applanation tonometry. This will be assessed at baseline and in response to peroral application of Bosentan or placebo.

The study objective is therefor, to evaluate the contribution of ET-1 to ocular blood flow dysregulation in patients with open-angle glaucoma.

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Key information

Conditions

Glaucoma Blood Flow Velocity Eye Diseases Ocular Hypertension

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Department of Clinical Pharmacology, Medical University of Vienna

Vienna, A-1090, Austria

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Men and women aged over 18 years
Normal findings in the medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant
Inclusion criteria for patients is primary open angle glaucoma defined as pathological optic disc appearance and characteristic visual field loss
Men and women will be included in equal parts
Ametropia of less than 6 diopters and anisometropia of less than 2 diopters

Exclusion criteria

(glaucoma patients)

Abuse of alcoholic beverages, participation in a clinical trial in the 3 weeks preceding the study
Smoking
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
Elevated liver enzymes AST and ALT
Blood donation during the previous 3 weeks
Ametropy more than 6 dpt
Systemic treatment with, oral antikoagulation, Glibenclamid or vasoactive drugs
History of IOP > 30 (untreated)
Presence of intraocular pathology other than glaucoma
Advanced visual field defect defined as MD >-10
Presence of PEX (pseudoexfoliation) glaucoma and pigment glaucoma
Ophthalmolgical surgery (including argon laser trabeculoplasty (ALT), trabeculectomy, deep sclerectomy) within the last 6 months before the study
Pregnancy
Diabetes mellitus

Exclusion criteria

(healthy controls)

Abuse of alcoholic beverages, participation in a clinical trial in the 3 weeks preceding the study
Smoking
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
Ametropy more than 6 dpt
Systemic treatment with oral anticoagulation, Glibenclamid or vasoactive drugs
Elevated liver enzymes AST and ALT
Pregnancy
Diabetes mellitus

Treatment and study plan

Bosentan

Drug

Bosentan (Tracleer 125mg Tabletts), peroral, dose: 500mg for 8 days

Primary outcomes

Optic nerve head blood flow (Laser Doppler Flowmetry) Choroidal blood flow(Laser interferometry, Laser Doppler Flowmetry) Retinal blood flow(Laser Doppler velocimetry, Retinal Vessel analyzer) Intraocular pressure (Applanation tonometry)

Time frame: study 1: ocular blood flow measurements once; study day 2: basline measurements, and after 120min, 180min, 240min after medication intake

Sponsors and collaborators

Lead sponsor

Medical University of Vienna

Other

Registry information

Official study title

Effects of Non-Specific Endothelin-A Receptor Blockade on Ocular Blood Flow in Patients With Glaucoma.

Important dates

Study start: 2007
Primary completion: 2007
Study completion: 2007
First posted: Jun 19, 2008
Registry last updated: Jun 19, 2008

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

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