STOP-RGCD: Stop Retinal Ganglion Cell Dysfunction Study

Sponsor

University of Miami (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02390284

Collaborator

National Eye Institute (NEI) (NIH)

500

Enrollment

Location

Arms

106

Anticipated Duration (Months)

4.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Glaucoma is a progressive disease resulting in blindness. Determining the onset of the disease, predicting its severity and the benefit of pressure lowering eye drops is key to clinical management aimed at maintaining useful vision with advancing age. This study will longitudinally monitor a population of glaucoma suspects (with positive factors for the disease but with normal vision) with noninvasive pattern electroretinogram (PERG) and other standard eye tests for glaucoma. The PERG measures the function of retinal ganglion cells (RGCs) that are the parent neurons of the optic nerve. RGCs may become dysfunctional before dying and their function restored with pressure-lowering eye drops. Glaucoma suspects with abnormal PERG will be randomized to treatment with eye drops, while those with normal PERG will be left untreated. All patients will be monitored with PERG, Optic Coherence Tomography (OCT) and other ancillary tests every 6 months over 4 years.

Condition or Disease	Intervention/Treatment	Phase
Glaucoma	Drug: Latanoprost Drug: Bimatoprost Drug: Travoprost Drug: Timolol Drug: Dorzolamide Drug: Brinzolamide Drug: Acetazolamide Drug: Methazolamide	Phase 3

Detailed Description

The PERG is recorded from small metallic buttons taped on the skin similarly to an electrocardiogram, with the difference that the electrodes are around the eyes.

The only physical contact you will experience is a gentle cleaning of the skin with an alcohol prep pad. During the test you must look with both eyes at a Television (TV) display for about 3 minutes. During the follow up period you may be asked to take one more PERG test lying down in a bed.

This will cause a momentary increase of your eye pressure similar to the one that occurs during your normal sleep. This may help to understand whether or not your optic nerve functions normally when the pressure in your eye increases. For OCT evaluation, the pupil has to be dilated with drops as you did before for your eye exam. You have to briefly look at a mark inside the instrument one eye at a time.

PERG and OCT will be performed during the same day of your visit with the eye doctor. If you have already done these tests in the past, as part of another study or as part of your standard treatment, the results of these tests will be obtained from your record, and be included in this study.

If you are a participant in the Observation Group, you will be monitored with PERG, OCT, and standard clinical examinations every six months until close of study. If you are a participant in the Medication Group you will be also treated with eye drop medicines.

RISKS:

There are certain risks and discomforts that may be associated with this research. You should be aware that you are at risk of developing glaucoma whether you participate in the study or not. It is not known whether the risk of developing glaucoma is reduced by eye drops to lower eye pressure; the study will attempt to answer this question.

For the PERG, the only significant risk to you is a small chance of a rash to the cleansing agent for skin electrodes, which should go away without treatment. For OCT, there is a rare risk to you of an allergic reaction to the drops used to dilate your pupils. The risk is even lower if you did not have any reaction during your previous eye exams. In case of an allergic reaction, your eye doctor will immediately treat it. If you had previous problems with pupil dilation, you may wish to speak to your eye doctor about the option of doing this additional test.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

500 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Stop Retinal Ganglion Cell Dysfunction Study

Actual Study Start Date :

Sep 1, 2015

Anticipated Primary Completion Date :

Jul 1, 2024

Anticipated Study Completion Date :

Jul 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Abnormal PERG Untreated Participants recognized as Glaucoma suspects with an abnormal PERG test who have been assigned to not receive therapy or intervention.
Experimental: Abnormal PERG Treated Participants recognized as Glaucoma suspects with an abnormal PERG test who have been assigned to receive one or more drops in each eye in order to reduce the intraocular pressure by 20%. Drugs could be: Latanoprost 1 drop Once a day (QD) Bimatoprost 1 drop QD Travoprost 1 drop QD Timolol 1 drop Twice a day (BID) Dorzolamide 1 drop Three times a day (TID) Brinzolamide 1 drop BID Acetazolamide and Methazolamide depends on clinicians evaluation. If Clinicians consider necessary, he/she might combine 2 drugs in order to get the desired intraocular pressure.	Drug: Latanoprost Lower intraocular pressure (IOP) by increasing outflow of fluid from the eye. Other Names: Xalatan Drug: Bimatoprost Lower intraocular pressure by increasing outflow of fluid from the eye. Other Names: Lumigan Drug: Travoprost Lower intraocular pressure by increasing outflow of fluid from the eye. Other Names: Travatan Drug: Timolol Lower intraocular pressure by decreasing production of fluid Other Names: Timoptic Drug: Dorzolamide Lowers intraocular pressure by decreasing intraocular fluid production Other Names: Trusopt Drug: Brinzolamide Lowers intraocular pressure by decreasing intraocular fluid production Other Names: Azopt Drug: Acetazolamide Lowers intraocular pressure by decreasing intraocular fluid production Other Names: Diamox Drug: Methazolamide Lowers intraocular pressure by decreasing intraocular fluid production Other Names: Neptazane
No Intervention: Normal Patients with a normal PERG test that will go through the study under observation.

Arm

Intervention/Treatment

No Intervention: Abnormal PERG Untreated

Participants recognized as Glaucoma suspects with an abnormal PERG test who have been assigned to not receive therapy or intervention.

Experimental: Abnormal PERG Treated

Participants recognized as Glaucoma suspects with an abnormal PERG test who have been assigned to receive one or more drops in each eye in order to reduce the intraocular pressure by 20%. Drugs could be: Latanoprost 1 drop Once a day (QD) Bimatoprost 1 drop QD Travoprost 1 drop QD Timolol 1 drop Twice a day (BID) Dorzolamide 1 drop Three times a day (TID) Brinzolamide 1 drop BID Acetazolamide and Methazolamide depends on clinicians evaluation. If Clinicians consider necessary, he/she might combine 2 drugs in order to get the desired intraocular pressure.

Drug: Latanoprost

Lower intraocular pressure (IOP) by increasing outflow of fluid from the eye.

Other Names:

Xalatan

Drug: Bimatoprost

Lower intraocular pressure by increasing outflow of fluid from the eye.

Other Names:

Lumigan

Drug: Travoprost

Lower intraocular pressure by increasing outflow of fluid from the eye.

Other Names:

Travatan

Drug: Timolol

Lower intraocular pressure by decreasing production of fluid

Other Names:

Timoptic

Drug: Dorzolamide

Lowers intraocular pressure by decreasing intraocular fluid production

Other Names:

Trusopt

Drug: Brinzolamide

Lowers intraocular pressure by decreasing intraocular fluid production

Other Names:

Azopt

Drug: Acetazolamide

Lowers intraocular pressure by decreasing intraocular fluid production

Other Names:

Diamox

Drug: Methazolamide

Lowers intraocular pressure by decreasing intraocular fluid production

Other Names:

Neptazane

No Intervention: Normal

Patients with a normal PERG test that will go through the study under observation.

Outcome Measures

Primary Outcome Measures

Change in retinal nerve fiber layer thickness [Baseline, 4 years]
As measured by Optical Coherence Tomography

Secondary Outcome Measures

Change in Pattern Electroretinogram Amplitude [Baseline, 4 years]
Assessed via Pattern Electroretinogram in microvolts
Change in Pattern Electroretinogram Phase [Baseline, 4 years]
Assessed via Pattern Electroretinogram in degrees

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Age 18 to 85 years, inclusive
Refractive errors within -5 to +3 diopters
Best corrected visual acuity (BCVA) better than or equal to 20/30 (Snellen)
Normal standard automated perimetry (SAP) according to the Ocular Hypertension Treatment Study (OHTS) criteria15 (reliability < 15% on all indices, normality > 5% on all global indices in two consecutive sessions 6 months apart)
Minimum untreated Intraocular pressure IOP of 15 mm Hg
Glaucoma Suspect Status defined as one or more of the following:

Glaucomatous optic disc appearance (vertical cup-to-disc ratio [C/D] ≥0.5
Cup disc ratio asymmetry ≥0.2
Localized thinning of the disc
Presence or history of splinter disc hemorrhage
Moderately increased IOP (>21 to <28 mm Hg).
Family history of vision loss for glaucoma

Exclusion Criteria:

Age-related macular degeneration
Diabetes
Parkinson's disease
Multiple sclerosis
Unwilling or unable to give consent, unwilling to accept randomization, or unable to return for scheduled protocol visits.
Pregnant or nursing women.
Currently using prescribed pressure lowering medicines and unwilling to be withdrawn from them.
An OHTS risk score high enough in the judgment of the ophthalmologist or optometrist managing the patient to recommend pressure lowering medicine to the patient and not randomization.
An OCT abnormal enough in a pattern consistent with glaucoma.