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

This study has been completed.
Sponsor:
Information provided by:
Chicago Center for Vision Research
ClinicalTrials.gov Identifier:
NCT00317577
First received: April 23, 2006
Last updated: NA
Last verified: April 2006
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Glaucoma, Open Angle
Drug: brimonidine, timolol
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Chicago Center for Vision Research:

Primary Outcome Measures:
  • 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:
  • 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

Estimated Enrollment: 160
Study Start Date: December 1998
Estimated Study Completion Date: May 2004
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.

  Eligibility

Ages Eligible for Study:   30 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00317577

Locations
United States, Arkansas
Little Rock Eye Clinic
Little Rock, Arkansas, United States, 72205
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
Bascom Palmer Eye Institute
Palm Beach Gardens, Florida, United States, 33418
United States, Illinois
University Eye Specialists
Chicago, Illinois, United States, 60611
University of Chicago
Chicago, Illinois, United States, 60637
Wheaton Eye Clinic
Wheaton, Illinois, United States, 60187
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, New York
New York Eye & Ear Infirmary
New York, New York, United States, 10003
United States, Pennsylvania
Wills Eye Hospital
Philadelphia, Pennsylvania, United States, 19107
Scheie Eye Institute University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, South Dakota
Black Hills Regional Eye Institute
Rapid City, South Dakota, United States, 57701
United States, Texas
Cullen Eye Institute Baylor University
Houston, Texas, United States, 77030
Sponsors and Collaborators
Chicago Center for Vision Research
Investigators
Study Chair: Theodore Krupin, M.D. Feinberg School of Medicine, Northwestern University
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00317577     History of Changes
Other Study ID Numbers: CCVR-0020
Study First Received: April 23, 2006
Last Updated: April 23, 2006
Health Authority: United States: Institutional Review Board

Keywords provided by Chicago Center for Vision Research:
Low-pressure glaucoma
Normal tension glaucoma
Neuroprotection
Brimonidine
Visual field progression

Additional relevant MeSH terms:
Glaucoma
Glaucoma, Open-Angle
Ocular Hypertension
Eye Diseases
Brimonidine
Timolol
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Adrenergic beta-Antagonists
Adrenergic Antagonists
Anti-Arrhythmia Agents

ClinicalTrials.gov processed this record on September 30, 2014