Effects of Non-Specific Endothelin-A Receptor Blockade on Ocular Blood Flow in Patients With Glaucoma
Information source: Medical University of Vienna
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Glaucoma; Blood Flow Velocity
Intervention: bosentan (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Medical University of Vienna Official(s) and/or principal investigator(s): Gabriele Fuchsjager-Mayrl, MD, Principal Investigator, Affiliation: Department of Clinical Pharmacology, Medical University of Vienna
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.
Clinical Details
Official title: Effects of Non-Specific Endothelin-A Receptor Blockade on Ocular Blood Flow in Patients With Glaucoma.
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment
Primary outcome: 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)
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
Department of Clinical Pharmacology, Medical University of Vienna, Vienna A-1090, Austria
Additional Information
Starting date: April 2007
Last updated: June 18, 2008
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