Clinical trial NCT02390284: Stop Retinal Ganglion Cell Dysfunction Study
Official title: Stop Retinal Ganglion Cell Dysfunction Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Glaucoma
Keywords: RGCD
Glaucoma Suspect
Lead sponsor: University of Miami
Sponsor class: OTHER
Collaborators: name: National Eye Institute (NEI)
First posted: 2015-03-17
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Eligibility criteria: Inclusion Criteria:

1. Age 18 to 85 years, inclusive
2. Refractive errors within -5 to +3 diopters
3. Best corrected visual acuity (BCVA) better than or equal to 20/30 (Snellen)
4. 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)
5. Minimum untreated Intraocular pressure IOP of 15 mm Hg
6. 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:

1. Age-related macular degeneration
2. Diabetes
3. Parkinson's disease
4. Multiple sclerosis
5. Unwilling or unable to give consent, unwilling to accept randomization, or unable to return for scheduled protocol visits.
6. Pregnant or nursing women.
7. Currently using prescribed pressure lowering medicines and unwilling to be withdrawn from them.
8. 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.
9. An OCT abnormal enough in a pattern consistent with glaucoma.

Primary outcomes:
measure: Change in retinal nerve fiber layer thickness
timeFrame: Baseline, 4 years
Secondary outcomes:
measure: Change in Pattern Electroretinogram Amplitude
timeFrame: Baseline, 4 years
measure: Change in Pattern Electroretinogram Phase
timeFrame: Baseline, 4 years
Other outcomes:
Locations:
city: Miami
country: United States
facility: Bascom Palmer Eye Institute - University of Miami
state: Florida
Study officials:
affiliation: University of Miami
name: Vittorio Porciattti, DSc
role: PRINCIPAL_INVESTIGATOR
References: