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

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ClinicalTrials.gov Identifier: NCT00317577
Recruitment Status : Completed
First Posted : April 25, 2006
Last Update Posted : April 25, 2006
Sponsor:
Information provided by:
Chicago Center for Vision Research

Tracking Information
First Submitted Date  ICMJE April 23, 2006
First Posted Date  ICMJE April 25, 2006
Last Update Posted Date April 25, 2006
Study Start Date  ICMJE December 1998
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE
 (submitted: April 23, 2006)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: April 23, 2006)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Medical Treatment of Low-Pressure (Normal Tension) Glaucoma
Official Title  ICMJE 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
Brief Summary

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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
Condition  ICMJE Glaucoma, Open Angle
Intervention  ICMJE Drug: brimonidine, timolol
Study Arms  ICMJE Not Provided
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Enrollment  ICMJE
 (submitted: April 23, 2006)
160
Original Enrollment  ICMJE Same as current
Study Completion Date  ICMJE May 2004
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00317577
Other Study ID Numbers  ICMJE CCVR-0020
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE Chicago Center for Vision Research
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Theodore Krupin, M.D. Feinberg School of Medicine, Northwestern University
PRS Account Chicago Center for Vision Research
Verification Date April 2006

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP