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

NCT00275756 | Withdrawn DMC

• 1 other identifier: OPHT-040106
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Glaucoma

Keywords

Ocular Physiology; Brimonidine; Timoptic; Dorzolamide; ocular blood flow; Regional Blood Flow

Outcome Measures

Primary Outcomes (1)

• Ocular perfusion pressure - ONH blood flow relationship

  on 2 study days

Secondary Outcomes (1)

• Composite measure: Blood pressure, heart rate

  on 2 study days

Study Arms (3)

1

EXPERIMENTAL

Drug: Timolol (drug); Device: Laser Doppler flowmetry; Device: Goldmann applanation tonometer; Procedure: Suction cup method

2

EXPERIMENTAL

Drug: dorzolamide (drug); Device: Laser Doppler flowmetry; Device: Goldmann applanation tonometer; Procedure: Suction cup method

3

EXPERIMENTAL

Drug: brimonidine (drug); Device: Laser Doppler flowmetry; Device: Goldmann applanation tonometer; Procedure: Suction cup method

Interventions

Timolol (drug) 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

1

dorzolamide (drug) DRUG

Dorzolamide (2%, carbonic anhydrase inhibitor, Trusopt®, Laboratoires Merck Sharp \& Dohme - Chibret, France), dose: 1 drop in one eye twice daily for two weeks

2

brimonidine (drug) DRUG

Brimonidine (0.2%. alpha-2 adrenergic agonist, Alphagan®, Allergan Pharmaceuticals, Westport, Ireland), dose: 1 drop in one eye twice daily for two weeks

3

Laser Doppler flowmetry DEVICE

blood flow measurements at the temporal neuroretinal rim of the optic nerve head, in total 4x 9 minutes on 2 study days

1; 2; 3

Goldmann applanation tonometer DEVICE

intraocular pressure measurements, in total 2x 5 measurements on two study days

1; 2; 3

Suction cup method PROCEDURE

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

1; 2; 3

Eligibility Criteria

• Age: 19 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Department of Clinical Pharmacology

Vienna, A-1090, Austria

Location

MeSH Terms

Conditions

Glaucoma

Interventions

Timolol; Pharmaceutical Preparations; dorzolamide; Brimonidine Tartrate; Laser-Doppler Flowmetry

Condition Hierarchy (Ancestors)

Ocular Hypertension; Eye Diseases

Intervention Hierarchy (Ancestors)

Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Thiadiazoles; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Morpholines; Oxazines; Quinoxalines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Rheology; Investigative Techniques

Study Officials

• Gabriele Fuchsjaeger-Mayrl, MD

  Department of Clinical Pharmacology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 11, 2006
• First Posted: January 12, 2006
• Study Start: September 1, 2008
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: November 21, 2014

Record last verified: 2014-11

Locations

AU (1)