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

NCT00701597 | Completed Phase 1 DMC

• 1 other identifier: OPHT-020606
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Glaucoma; Blood Flow Velocity

Keywords

ocular blood flow dysregulation, glaucoma, endothelin-1

Outcome Measures

Primary Outcomes (1)

• 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

Interventions

bosentan DRUG

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Men and women will be included in equal parts
• Ametropia of less than 6 diopters and anisometropia of less than 2 diopters

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Department of Clinical Pharmacology, Medical University of Vienna

Vienna, A-1090, Austria

Location

MeSH Terms

Conditions

Glaucoma

Interventions

Bosentan

Condition Hierarchy (Ancestors)

Ocular Hypertension; Eye Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Gabriele Fuchsjager-Mayrl, MD

  Department of Clinical Pharmacology, Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 18, 2008
• First Posted: June 19, 2008
• Study Start: April 1, 2007
• Primary Completion: September 1, 2007
• Study Completion: October 1, 2007
• Last Updated: June 19, 2008

Record last verified: 2008-06

Locations

AU (1)