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

This study has been completed.
Sponsor:
Information provided by:
Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT00701597
First received: June 18, 2008
Last updated: NA
Last verified: June 2008
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Glaucoma
Blood Flow Velocity
Drug: bosentan
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
Official Title: Effects of Non-Specific Endothelin-A Receptor Blockade on Ocular Blood Flow in Patients With Glaucoma.

Resource links provided by NLM:


Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 28
Study Start Date: April 2007
Study Completion Date: October 2007
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: bosentan
    Bosentan (Tracleer 125mg Tabletts), peroral, dose: 500mg for 8 days
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00701597

Locations
Austria
Department of Clinical Pharmacology, Medical University of Vienna
Vienna, Austria, A-1090
Sponsors and Collaborators
Medical University of Vienna
Investigators
Principal Investigator: Gabriele Fuchsjager-Mayrl, MD Department of Clinical Pharmacology, Medical University of Vienna
  More Information

No publications provided

Responsible Party: Gabriele Fuchsjaeger-Mayrl, Departnebt of Clinical Pharmacology, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT00701597     History of Changes
Other Study ID Numbers: OPHT-020606
Study First Received: June 18, 2008
Last Updated: June 18, 2008
Health Authority: Austria: Agency for Health and Food Safety

Keywords provided by Medical University of Vienna:
ocular blood flow dysregulation, glaucoma, endothelin-1

Additional relevant MeSH terms:
Glaucoma
Eye Diseases
Ocular Hypertension

ClinicalTrials.gov processed this record on October 23, 2014