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

Glaucoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00701597
• Other study ID #: OPHT-020606
• Status: Completed
• Phase: Phase 1
• First received: June 18, 2008
• Last updated: June 18, 2008
• Start date: April 2007
• Est. completion date: October 2007

Study information

• Verified date: June 2008
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Agency for Health and Food Safety
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: October 2007
• Est. primary completion date: September 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Blood Flow Velocity
• Glaucoma

Intervention

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

Locations

Country	Name	City	State
Austria	Department of Clinical Pharmacology, Medical University of Vienna	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Vienna

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)		study 1: ocular blood flow measurements once; study day 2: basline measurements, and after 120min, 180min, 240min after medication intake	Yes