Official Title: “Effects of Common Topical Glaucoma Therapy on Optic Nerve Head Blood Flow Autoregulation During Increased Arterial Blood Pressure and Artificially Elevated Intraocular Pressure in Healthy Humans”

Background

Autoregulation is the ability of a vascular bed to maintain blood flow despite changes in perfusion pressure. The existence of an effective autoregulation in the optic nerve circulation has been shown in animals and humans. The exact mechanism behind this autoregulation is still unknown. The motive for the investigation of optic nerve head (ONH) blood flow autoregulation is to enhance the understanding of pathologic eye conditions associated with ocular vascular disorders. To clarify the regulatory mechanisms of ONH microcirculation is of critical importance to understand the pathophysiology of glaucoma, because there is evidence that glaucoma is associated with optic nerve head ischemia. Several studies indicate that a disturbed autoregulation might contribute to glaucomatous optic neuropathy. Currently, five classes of intraocular pressure (IOP) reducing drugs are available for topical therapy in patients with glaucoma or elevated intraocular pressure.

These drugs have also vasoactive properties, which may influence both the resting ocular circulation and the autoregulatory mechanisms of blood flow during changes in ocular perfusion pressure.

Study objective

To investigate the influence of common topical glaucoma therapy on ONH blood flow regulation during changes in IOP and systemic arterial blood pressure.

Study Type: Interventional

Study Design: Basic Science, Randomized, Double Blind (Subject, Investigator), Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: December 2009

Intervention(s) in this Clinical Trial

• Drug: Timolol (drug)
  • Timolol (0.5%, non-selective beta-blocker, Timoptic®, Merck Sharp & Dohme, Haarlem, Netherlands), dose 1 drop in one eye twice daily for two weeks
• Drug: dorzolamide (drug)
  • Dorzolamide (2%, carbonic anhydrase inhibitor, Trusopt®, Laboratoires Merck Sharp & Dohme - Chibret, France), dose: 1 drop in one eye twice daily for two weeks
• Drug: brimonidine (drug)
  • Brimonidine (0.2%. alpha-2 adrenergic agonist, Alphagan®, Allergan Pharmaceuticals, Westport, Ireland), dose: 1 drop in one eye twice daily for two weeks
• Device: Laser Doppler flowmetry
  • blood flow measurements at the temporal neuroretinal rim of the optic nerve head, in total 4x 9 minutes on 2 study days
• Device: Goldmann applanation tonometer
  • intraocular pressure measurements, in total 2x 5 measurements on two study days
• Procedure: Suction cup method
  • The IOP will be raised by an 11 mm diameter, standardized suction cup placed on the temporal sclera with the anterior edge at least 1 mm from the limbus; 4x 8 minutes on 2 study days

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
• Experimental: 2
• Experimental: 3

Primary Measures

• Ocular perfusion pressure - ONH blood flow relationship
  • Time Frame: on 2 study days
    Safety Issue?: No

Secondary Measures

• Blood pressure, heart rate
  • Time Frame: on 2 study days
    Safety Issue?: Yes

Inclusion Criteria:

• Men aged between 19 and 35 years, nonsmokers
• Body mass index between 15th and 85th percentile
• Normal findings in the medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant
• Normal ophthalmic findings, ametropia < 1 Dpt.

Exclusion Criteria:

• Regular use of medication, abuse of alcoholic beverages, participation in a clinical trial in the 3 weeks preceding the study
• Treatment in the previous 3 weeks with any drug
• Symptoms of a clinically relevant illness in the 3 weeks before the first study day
• Blood donation during the previous 3 weeks
• Presence of intraocular pathology: ocular hypertension, glaucoma, retinal vasculopathy or other retinal diseases

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 19 Years

Maximum Age for this Clinical Trial: 35 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Medical University of Vienna

Overall Clinical Trial Officials and Contacts

Gabriele Fuchsjaeger-Mayrl, MD Principal Investigator Department of Clinical Pharmacology  

Overall Contact: Gerhard Garhofer, MD + 43 1 40400 2981 gerhard.garhoefer@meduniwien.ac.at

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00275756

Study ID Number: OPHT-040106

ClinicalTrials.gov Identifier: NCT00275756

Health Authority: Austria: Agency for Health and Food Safety