Study of Medical Treatment of Low-Pressure (Normal Tension) Glaucoma
|ClinicalTrials.gov Identifier: NCT00317577|
Recruitment Status : Completed
First Posted : April 25, 2006
Last Update Posted : April 25, 2006
|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
||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
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|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|
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.
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
Primary Purpose: Treatment
|Condition ICMJE||Glaucoma, Open Angle|
|Intervention ICMJE||Drug: brimonidine, timolol|
|Study Arms ICMJE||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Original Enrollment ICMJE||Same as current|
|Study Completion Date ICMJE||May 2004|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
Either eye patient exclusion:
Single eye exclusion:
|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|
|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|
|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