Study of Medical Treatment of Low-Pressure (Normal Tension) Glaucoma

April 23, 2006 updated by: Chicago Center for Vision Research

A Multicenter, Double-Masked, 2-Arm Parallel Group Study Comparing the Effect of Brimonidine 0.2% Versus Timolol 0.5% on Visual Field Stability in Patients With Low-Pressure Glaucoma

Low-pressure (normal tension) glaucoma is a type of open-angle glaucoma resulting in damage to the optic nerve and abnormalities of the visual field. Eye (intraocular) pressure in this type of glaucoma is not higher than that usually considered to be normal (less than 21 mmHg) for the eye. The present treatment of low-pressure glaucoma is also directed to lowering the "normal" eye pressure. Both medications in this study, brimonidine and timolol, lower eye pressure.

Laboratory research over the past decade indicates the potential to treat glaucoma not only by lowering eye pressure, but with treatments aimed at the damage occurring at the optic nerve. One group of drugs, selective alpha2-adrenergic agonists, have been shown in laboratory animals to protect against the effects of nerve damage following local stroke. Brimonidine, one of the medications in the current study, is a selective alpha2-adrenergic agonist which protects against damage to optic nerve in animal models of glaucoma..

The hypothesis of the present study is that brimonidine eye drops provide protection to the damaged optic nerve independent of lowering eye pressure in patients with low-pressure glaucoma. This will be determined by (1) measuring eye pressure, (2) performing visual field examinations, and (3) examination of the optic nerve.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The term glaucoma describes a specific pattern of optic nerve head and visual field damage caused by a number of different diseases of the eye, most (but not all) of which are associated with an elevated eye pressure. Glaucoma is currently considered to be a progressive neurodegenerative disorder. Low-pressure glaucoma (LPG) is a type of open-angle glaucoma (OAG) with progressive visual field and optic nerve damage despite an untreated eye pressure in the statistically normal (mean 15.9, SD 2.9 mmHg) range, usually less than 21 mmHg. Therefore, in this condition, pressure-independent mechanisms (e.g., vascular or structural defects of the optic nerve) may be the main, if not the sole, cause of the optic neuropathy. LPG represents 6.7% to 68.3% of all OAGs.

Current glaucoma treatment is directed to lowering eye pressure using medical therapy (eye drops), laser treatment, and/or surgery, to a level that stops progressive optic nerve damage. The efficacy of lowering eye pressure in LPG has been reported. Both protocol medical treatments, brimonidine and timolol, show similar efficacy to lower eye pressure.

Laboratory research over the past decade indicates the potential to manage glaucoma not only by lowering eye pressure, but with treatment modalities aimed at the damage occurring at the optic nerve. Possible therapies may include agents effective as neuronal protectants to increase or prolong the survival rate of injured retinal ganglion cells. Treatments could also be directed to the rescue of nerve fibers from secondary degeneration, as stimulants to expand dendritic fields, and to promote nerve regeneration or neural transplantation.

Selective α2-adrenergic agonists have been shown to have a neuroprotective effect in animal models of focal cerebral ischemia. Brimonidine is reported to protect the optic nerve and retinal ganglion cells from secondary degeneration following a partial crush lesion to the adult rat optic nerve. One molecular mechanism for this neuroprotection may relate to up-regulation of neuronal survival factors. In rats, systemic α2-adrenergic agonists induce basic fibroblast growth factor mRNA in the retina. Treatment with α2-agonists before and during constant light exposure reduces retinal photoreceptor degeneration in albino rats. Animal studies demonstrate that topical administration of brimonidine results in pharmacologic concentrations of drug in the vitreous (100-170 nM). Therefore, ocular dosing with brimonidine provides a route for drug delivery to the retina in amounts sufficient to bind and activate the α2-adrenoceptor and provide a neuroprotective effect.

The study hypothesis is to evaluate the ability of topical treatment with 0.2% brimonidine, a highly selective α2-adrenergic agonist, to impart neuroprotection to the damaged optic nerve in patients with LPG. Comparison is made to 0.5% timolol, a nonselective β-adrenergic antagonist, without reported neuroprotective properties. Patients will be randomly assigned to twice daily double-masked treatment with one of these drugs. Neuroprotection will be assessed by evaluation of automated static visual fields performed at 4 month intervals for 4 years of treatment.

Study Type

Interventional

Enrollment

160

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Little Rock Eye Clinic
    • Florida
      • Gainesville, Florida, United States, 32610
        • University of Florida
      • Palm Beach Gardens, Florida, United States, 33418
        • Bascom Palmer Eye Institute
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago
      • Chicago, Illinois, United States, 60611
        • University Eye Specialists
      • Wheaton, Illinois, United States, 60187
        • Wheaton Eye Clinic
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University
    • New York
      • New York, New York, United States, 10003
        • New York Eye & Ear Infirmary
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Wills Eye Hospital
      • Philadelphia, Pennsylvania, United States, 19104
        • Scheie Eye Institute University of Pennsylvania
    • South Dakota
      • Rapid City, South Dakota, United States, 57701
        • Black Hills Regional Eye Institute
    • Texas
      • Houston, Texas, United States, 77030
        • Cullen Eye Institute Baylor University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

28 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age: 30 years or older.
  • Low-pressure glaucoma in at least one eye: untreated IOP < 21 mmHg, glaucomatous field loss on Humphrey 24-2 perimetry, and optic disc cupping.
  • Best corrected visual acuity at least 20/40 in at least one eye.
  • At least two visual fields within the 6 months prior to enrollment.
  • Phakic or pseudophakic (cataract surgery > one year to enrollment) eye.

Exclusion Criteria:

Either eye patient exclusion:

  • Past history of confirmed treated or untreated applanation IOP > 21 mmHg.
  • Untreated IOP of > 21 mmHg on diurnal curve on Study Day 0.
  • Untreated IOP > 4 mmHg difference between the two eyes.
  • Extensive field damage: MD > 15 dB or threat fixation in both hemi fields.
  • Evidence of exfoliation or pigment dispersion.
  • History of angle-closure or occludable gonioscopic anterior chamber angle.
  • Prior filtration surgery.
  • Prior laser iridotomy.
  • Laser trabeculoplasty < 6 months prior enrollment or for an IOP > 21 mmHg.
  • History of chronic inflammatory eye diseases (e.g., scleritis, uveitis).
  • History or signs of intraocular trauma.
  • Severe or potentially progressive retinal disease.
  • Any abnormality preventing reliable applanation tonometry.
  • History of hypersensitivity to study medications or their components.
  • Current use of any ophthalmic, dermatologic or systemic steroid preparation.
  • Therapy with another investigational agent within the past 30 days.

Single eye exclusion:

  • Cataract surgery within the past year.
  • Aphakia.
  • Only sighted eye.

Concomitant conditions:

  • Resting pulse < 50 beats per minute.
  • Unstable or uncontrolled cardiovascular, renal, or pulmonary disease.
  • Recent heart attack or stroke.
  • Women contemplating pregnancy, who are pregnant or are a nursing mother.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
To compare changes in automated static visual field decibel values at 4 month intervals over 4 years of monotherapy with either brimonidine or timolol eye drops.

Secondary Outcome Measures

Outcome Measure
To characterize the intraocular pressure throughout the study period.
To characterize optic disc changes (e.g., cupping and disc hemorrhages) over the 4 years of treatment with brimonidine or timolol.
To follow the safety parameters throughout the study period.
To determine risk factors for visual field progression in low-pressure glaucoma

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chicago Center for Vision Research

Investigators

  • Study Chair: Theodore Krupin, M.D., Northwestern University Feinberg School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 1998

Study Completion

May 1, 2004

Study Registration Dates

First Submitted

April 23, 2006

First Submitted That Met QC Criteria

April 23, 2006

First Posted (Estimate)

April 25, 2006

Study Record Updates

Last Update Posted (Estimate)

April 25, 2006

Last Update Submitted That Met QC Criteria

April 23, 2006

Last Verified

April 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CCVR-0020

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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