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

Medical University of Vienna

Status and phase

Completed

Phase 1

Conditions

Glaucoma

Blood Flow Velocity

Treatments

Drug: bosentan

Study type

Interventional

Funder types

Other

Identifiers

NCT00701597

OPHT-020606

Details and patient eligibility

About

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.

Enrollment

28 patients

Sex

All

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion criteria

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