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

Sponsor

Medical University of Vienna (Other)

Overall Status

Withdrawn

CT.gov ID

NCT00275756

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Glaucoma	Drug: Timolol (drug) Drug: dorzolamide (drug) Drug: brimonidine (drug) Device: Laser Doppler flowmetry Device: Goldmann applanation tonometer Procedure: Suction cup method	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Basic Science

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

Study Start Date :

Sep 1, 2008

Actual Primary Completion Date :

Nov 1, 2014

Actual Study Completion Date :

Nov 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	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 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
Experimental: 2	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 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
Experimental: 3	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

Arm

Intervention/Treatment

Experimental: 1

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

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

Experimental: 2

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

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

Experimental: 3

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

Outcome Measures

Primary Outcome Measures

Ocular perfusion pressure - ONH blood flow relationship [on 2 study days]

Secondary Outcome Measures

Composite measure: Blood pressure, heart rate [on 2 study days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years to 35 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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