Clinical trial NCT02984813: Safety and Efficacy of Anti-Oxidants and Anti-inflammatory Agents in Glaucoma and Diabetic Retinopathy
Official title: Measurement of Oxidative Stress of Retinal Ganglion Cells With and Without Anti-oxidants and Anti-inflammatory Agents in Patients With Glaucoma and Diabetic Retinopathy as Determined by Mitochondrial Flavoprotein Fluorescence
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Open-angle Glaucoma
Diabetic Retinopathy
Lead sponsor: The New York Eye & Ear Infirmary
Sponsor class: OTHER
First posted: 2016-12-07
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study is a multi-armed protocol designed to evaluate the safety and efficacy of two different combinations of nutritional supplements (study drug) (Glauco-Health and Glauco-Select) chosen for their potential to protect retinal ganglion cells against oxidative stress, low-grade inflammation, and mitochondrial dysfunction in patients with open-angle glaucoma and diabetic retinopathy. Oxidative stress and retinal cellular dysfunction will be measured using a Retinal Metabolic Analyzer (RMA) in this randomized, single center, double masked study. Patients with glaucoma will be divided into three treatment arms randomized to receive either Glauco-Health, Glauco-Select, or placebo.

Detailed description: This investigation is using over the counter supplements. The investigation is intended only to evaluate their effect on the structure or function of mitochondria as it relates to the autofluorescence imaging being conducted in the study. They are not being studied to evaluate their ability to diagnose, cure, mitigate, or treat disease.

These ingredients in these combinations of nutritional supplements have also been reported beneficial in diabetic retinopathy. Patients with diabetic retinopathy will be added later as an additional arm and an amendment to this effect will be submitted when that portion of the study is ready to be initiated. That amendment will include background material, appropriate inclusion and exclusion criteria, informed consent, and references. At the current time, only the glaucoma proposal and glaucoma patients will be enrolled according to this submitted protocol.

Eligibility criteria: Inclusion Criteria:

1. Male or female of any race, at least 18 years of age.
2. Has provided verbal and written informed consent.
3. Able and willing to follow instructions, including participation in all study assessments and visits.
4. Eyes with moderate to severe primary open-angle glaucoma will be enrolled. Glaucoma severity will be graded using the WHO glaucoma staging system.

   1. OAG eyes are defined by clinical findings consistent with glaucomatous optic neuropathy (Ex: thinning, excavation, rim erosion or notching of the neuroretinal rim)
   2. Reproducible visual field defects on at least three examinations as measured by a glaucoma hemifield test (GHT) result outside normal limits and/or the presence of at least three consecutive test points on the pattern deviation plot with P\<1% and at least one at P\<0.05%, not including points on the edge of the field.
5. Both eyes will be enrolled.
6. Refractive error ≤5 diopters and astigmatism ≤3 diopters

Exclusion Criteria:

1. Comorbidity with other severe or chronic eye conditions that in the judgment of the investigator will interfere with study assignment, such as age-related macular degeneration, macular dystrophy, retinopathy from systemic diseases, marked ocular media opacities that obscure retinal imaging, etc.
2. BCVA \<20/200
3. Concurrent conjunctivitis, keratitis or uveitis
4. History of penetrating ocular trauma.
5. Subject uncooperativeness that restricts adequate examination of IOP, ocular fundus or anterior chamber.
6. Has a condition or history that, in the opinion of the investigator, may interfere significantly with the subject's participation in the study.
7. A woman who is pregnant, nursing an infant, or planning a pregnancy
8. Has a known adverse reaction and/or sensitivity to the study drug or its compound.

   a. Including: alpha lipoic acid, citicoline, Co-enzyme Q-10, Ginkgo biloba extract, grape seed extract, N-acetyl-cysteine, curcumin, green tea extract, and bilberry extract.
9. Currently enrolled in an investigational drug study or has used an investigational drug within 30 days prior to Visit 1.
10. Is planning on having surgery at any time throughout the study duration (90 days from initiation)
11. Is currently receiving chemotherapy
12. Has a history of diabetes mellitus, seizure(s), bleeding disorder(s)
13. Has a history of uncontrolled hypertension (≥180 systolic or ≥110 diastolic on two successive measures)
14. Has a history of any radiation around the eyes
15. Currently using anticoagulant/antiplatelet drugs (patients on coumadin, clopidogral (Plavix), and plasugrel (Effient) will be excluded but that patients taking aspirin will be allowed)
16. Unwilling or unable to cease using other anti-oxidative agents or drugs.
17. Dilated pupil diameter less than 5 millimeters
18. Fluorescein drop administration within 8 hours before imaging
19. History of cataract surgery in the 3 months prior to imaging
20. History of any other intraocular surgery within 4 months prior to enrollment
21. Corticosteroid or immunosuppressive therapy within 6-months prior to imaging
22. Lens opacity ≥grade 3 on ARLNS on standard photographs (Appendix 6)
23. History of vitrectomy
24. Monocular patients

Primary outcomes:
measure: Flavoprotein fluorescence index
timeFrame: 3 months
Secondary outcomes:
measure: Visual acuity
timeFrame: 3 months
measure: Humphrey visual field testing (24-2)
timeFrame: 3 months
Other outcomes:
Locations:
city: New York
country: United States
facility: New York Eye and Ear Infirmary of Mount Sinai
state: New York
Study officials:
affiliation: Shelley and Steven Einhorn Distinguished Chair Professor of Ophthalmology Surgeon Director Emeritus and Chief, Glaucoma Services The New York Eye and Ear Infirmary of Mount Sinai
name: Robert Ritch, MD
role: PRINCIPAL_INVESTIGATOR
References: