Glaucoma, Open AnglePhase 2NCT00317577
Study of Medical Treatment of Low-Pressure (Normal Tension) Glaucoma
A Phase 2 study testing brimonidine, timolol in people with Glaucoma, Open Angle, run by Chicago Center for Vision Research at 12 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 years and older
- Conditions the study is for
- Glaucoma, Open Angle
- What is being tested?
- brimonidine, timolol
- How many people
- 160 participants
- Where
- 12 sitesUnited States
- Study dates
- Dec 1998to May 2004
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 26Show fewer
- 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.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
University Eye Specialists
Chicago, Illinois, 60611
University of Chicago
Chicago, Illinois, 60637
University of Florida
Gainesville, Florida, 32610
Cullen Eye Institute Baylor University
Houston, Texas, 77030
Indiana University
Indianapolis, Indiana, 46202
Little Rock Eye Clinic
Little Rock, Arkansas, 72205
New York Eye & Ear Infirmary
New York, New York, 10003
Bascom Palmer Eye Institute
Palm Beach Gardens, Florida, 33418
Scheie Eye Institute University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Wills Eye Hospital
Philadelphia, Pennsylvania, 19107
Black Hills Regional Eye Institute
Rapid City, South Dakota, 57701
Wheaton Eye Clinic
Wheaton, Illinois, 60187
About this study
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
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.
Read the 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.
- Conditions
- Glaucoma, Open Angle
- Being tested
- brimonidine, timolol
- Keywords
- Low-pressure glaucoma, Normal tension glaucoma, Neuroprotection, Brimonidine, Visual field progression
- Medical subject headings
- Glaucoma, Open-Angle, Low Tension Glaucoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
brimonidine, timololDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
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 outcomes (4)
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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2006 (estimated)
- Study startDec 1998
- Study completionMay 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Glaucoma, Open AngleStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 160 participants
Sponsor and investigators
- Lead sponsor
- Chicago Center for Vision Research
- Sponsor type
- University, hospital or other
- Investigators
- Theodore Krupin, M.D., Study chair, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00317577
- Sponsor's protocol ID
- CCVR-0020
- Status last verified
- Apr 2006
- First submitted
- 23 Apr 2006
- Last updated
- 25 Apr 2006
- Results posted
- No
Publications
Krupin T, Liebmann JM, Greenfield DS, Rosenberg LF, Ritch R, Yang JW; Low-Pressure Glaucoma Study Group. The Low-pressure Glaucoma Treatment Study (LoGTS) study design and baseline characteristics of enrolled patients. Ophthalmology. 2005 Mar;112(3):376-85. doi: 10.1016/j.ophtha.2004.10.034.
PubMed 15745762Furlanetto RL, De Moraes CG, Teng CC, Liebmann JM, Greenfield DS, Gardiner SK, Ritch R, Krupin T; Low-Pressure Glaucoma Treatment Study Group. Risk factors for optic disc hemorrhage in the low-pressure glaucoma treatment study. Am J Ophthalmol. 2014 May;157(5):945-52. doi: 10.1016/j.ajo.2014.02.009. Epub 2014 Feb 7.
PubMed 24513094De Moraes CG, Liebmann JM, Greenfield DS, Gardiner SK, Ritch R, Krupin T; Low-pressure Glaucoma Treatment Study Group. Risk factors for visual field progression in the low-pressure glaucoma treatment study. Am J Ophthalmol. 2012 Oct;154(4):702-11. doi: 10.1016/j.ajo.2012.04.015. Epub 2012 Jul 25.
PubMed 22835512Krupin T, Liebmann JM, Greenfield DS, Ritch R, Gardiner S; Low-Pressure Glaucoma Study Group. A randomized trial of brimonidine versus timolol in preserving visual function: results from the Low-Pressure Glaucoma Treatment Study. Am J Ophthalmol. 2011 Apr;151(4):671-81. doi: 10.1016/j.ajo.2010.09.026. Epub 2011 Jan 22.
PubMed 21257146
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2006. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00317577
- Acronym / sponsor ID
- CCVR-0020
- Conditions
- Glaucoma, Open Angle
- Keywords
- Low-pressure glaucoma, Normal tension glaucoma, Neuroprotection, Brimonidine, Visual field progression
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 160 participants
- Lead sponsor
- Chicago Center for Vision ResearchUniversity, hospital or other
- Study start
- Dec 1998
- Study completion
- May 2004
- First posted
- 25 Apr 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 30 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (26 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| brimonidine, timolol | Drug | – |
Primary outcome
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.
4 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2006.
- Background: PubMed 15745762Krupin T, Liebmann JM, Greenfield DS, Rosenberg LF, Ritch R, Yang JW; Low-Pressure Glaucoma Study Group. The Low-pressure Glaucoma Treatment Study (LoGTS) study design and baseline characteristics of enrolled patients. Ophthalmology. 2005 Mar;112(3):376-85. doi: 10.1016/j.ophtha.2004.10.034.
- Derived from this study: PubMed 24513094Furlanetto RL, De Moraes CG, Teng CC, Liebmann JM, Greenfield DS, Gardiner SK, Ritch R, Krupin T; Low-Pressure Glaucoma Treatment Study Group. Risk factors for optic disc hemorrhage in the low-pressure glaucoma treatment study. Am J Ophthalmol. 2014 May;157(5):945-52. doi: 10.1016/j.ajo.2014.02.009. Epub 2014 Feb 7.
- Derived from this study: PubMed 22835512De Moraes CG, Liebmann JM, Greenfield DS, Gardiner SK, Ritch R, Krupin T; Low-pressure Glaucoma Treatment Study Group. Risk factors for visual field progression in the low-pressure glaucoma treatment study. Am J Ophthalmol. 2012 Oct;154(4):702-11. doi: 10.1016/j.ajo.2012.04.015. Epub 2012 Jul 25.
- Derived from this study: PubMed 21257146Krupin T, Liebmann JM, Greenfield DS, Ritch R, Gardiner S; Low-Pressure Glaucoma Study Group. A randomized trial of brimonidine versus timolol in preserving visual function: results from the Low-Pressure Glaucoma Treatment Study. Am J Ophthalmol. 2011 Apr;151(4):671-81. doi: 10.1016/j.ajo.2010.09.026. Epub 2011 Jan 22.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Theodore Krupin, M.D. study chair
Northwestern University
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing brimonidine, timolol in people with Glaucoma, Open Angle, run by Chicago Center for Vision Research at 12 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Apr 2006. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary 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.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00317577, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2006.