Diabetic Retinopathy Functional Evaluation Study: Monitoring Carotenoid Vitamins Treatment Using ERG

To evaluate the differences in retinal function as measured by ERG in diabetics with and without retinopathy 2) the ability of the Chromatic Electroretinogram (chERG) to detect changes in global retinal function following treatment with Carotenoid Vitamins supplement in patients with diabetic retinopathy (DR). 3) the ability of the Full Field flicker (ffERG) to detect changes in global retinal function following treatment with Carotenoid Vitamins supplement in patients with diabetic retinopathy (DR).

4) Changes in retinal function as observed by OCT-Angiography, following treatment with Carotenoid Vitamins supplement in patients with diabetic retinopathy (DR).

Study Overview

• Status: Recruiting
• Conditions: Diabetes; Diabetic Retinopathy
• Intervention / Treatment: Dietary supplement: DVS supplementation

Detailed Description

This prospective, study has cross-sectional analysis of ERG functions in a group of diabetics with and without retinopathy. Both Chromatic ERG and Full field ERG (NOVA, Diopsys, Inc. Pine Brook, NJ) will be utilized in the study. Subsequently individuals with an outside normal limit outcome on at least one ERG test will be invited to be part of the longitudinal study. Individuals with abnormal ERG results will be asked to take the carotenoid vitamin supplement (ZeaVision DVS supplement) and the baseline data will be compared to the values at one, three- and six-month follow-up.

The primary endpoint of a patient's follow-up will be at 6 months. The study will be performed at three sites. Western University of Health Sciences, Harpers Pointe Eye Associates (Externship site College of Optometry, Western University of Health Sciences) and Oklahoma College of Optometry, Northeastern State University, Tahlequah, Oklahoma.

The clinical study plan will be reviewed and approved by Eye Care Center of the Western University of Health Sciences Institutional Review Board (IRB). Harpers Pointe Eye Associates will be covered under an externship site of Western University of Health Sciences.

NSUOCO will apply for a separate IRB review at their own site.

• Study Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pinakin Davey, OD, PhD; Phone Number: 909-469-8473 |; Email: pdavey@westernu.edu
• Study Contact Backup: Name: Nathan Lighthizer, OD; Phone Number: 918-444-4007; Email: lighthiz@nsuok.edu

Study Locations

• United States
  • California
    • Pomona, California, United States, 91766
      • Recruiting
      • Western Universit5y of Health Sciences, College of Optometry
      • Contact: Pinakin G. Davey, OD, PhD; Phone Number: 901-831-1562; Email: contact@pinakin-gunvant.com
      • Contact: Ida Chung, OD, MSHE; Phone Number: 909-469-8687; Email: ichung@westernu.edu
  • Oklahoma
    • Tahlequah, Oklahoma, United States, 74464
      • Recruiting
      • Oklahoma College of Optometry, Northeastern State University
      • Contact: Nathan R. Lighthizer, OD; Phone Number: 918-444-4007; Email: lighthiz@nsuok.edu
      • Contact: Richard E. Castillo, OD; Phone Number: (918) 444-4038; Email: castillo@nsuok.edu
      • Principal Investigator: Pinakin Davey, OD, PhD
      • Principal Investigator: Nathan R. Lighhizer, OD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 21-80 years

  1. History of Diabetes for at least > 5years

  2. No retinopathy, Mild or Moderate Non-Proliferative diabetic retinopathy

     • Diabetes without retinopathy (Appendix A)
     • Mild to moderate NPDR as defined by the American Academy of Ophthalmology7 (Appendix A)

Exclusion Criteria:

• • History of any systemic or ophthalmic condition (other than diabetic retinopathy) capable of affecting vision

  • Presence of Diabetic Macular Edema
  • History of intraocular surgery, including macular or panretinal photocoagulation laser (except uncomplicated cataract or keratorefractive surgery more than 6 months prior to enrollment)
  • History of treatment affecting vision, influencing reaction time and/or drugs indicating severe general diseases (eg. Hydroxychloroquine, tamoxifen, dexamethasone, triamcinolone, fluocinolone, etc.)
  • Spherical refraction outside ±5.0 D or cylinder correction outside ±3.0 D
  • Inability to obtain reliable Chromatic ERG test
  • Pregnant and nursing women
  • Allergy to the supplement or any of its ingredients
  • Any subject that all ERG study tests or the OCT angiography cannot be obtained reliably.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: supplemented arm; Each subject will receive DVS formula, 2 softgels per day for 6 months.

Dietary supplement: DVS supplementation; Oral supplement. Each subject will be given the carotenoid supplement of DVS formula. The DVS formula consists of vitamins C, D3 and E (d-α tocopherol), zinc oxide, eicosapentaenoic acid, docosahexaenoic acid, α-lipoic acid (racemic mixture), coenzyme Q10, mixed tocotrienols/tocopherols, zeaxanthin, lutein, benfotiamine, N-acetyl cysteine, grape seed extract, resveratrol, turmeric root extract, green tea leaf, and Pycnogenol (patented French Maritime Pine Bark extract, sp Pinus pinaster, Horphag Research, Geneva, Switzerland). Supplements bottles will be labelled with a unique identification number for each subject and supplied by ZeaVision, LLC, Chesterfield, Missouri, USA. To assure that the participants do not have any issues with the vitamin supplement and to ensure adequate adherence to schedule of vitamin intake the participants will get regular phone calls from the study investigators (once every two weeks).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chromatic ERG (ChERG) Outcome Measurements: B wave and PhNR latency (milliseconds) Full field ERG outcome measurements and Chromatic ERG Outcome Measurements	The Chromatic Electroretinogram (chERG) and the full field ERG will be recorded using a commercially available system Diopsys® NOVA (Diopsys, Inc. Pine Brook, New Jersey). The Red-Blue stimulus will be presented using a mini-Ganzfeld handheld device. The entire process consists of two tests per eye, with twenty-five seconds allocated for each test; thus, the total duration of the test is one hundred seconds. The chERG will be consecutively recorded from both eyes by means of proprietary adhesive skin electrodes on the lower eyelid and forehead.	Change from Baseline to 6 months
Full-field flicker ERG (ffERG) Measurements: magnitude (microvolts) and the phase (milliseconds) and the area ratio for magnitude and the area ratio for Phase	The Flicker ERG will be recorded using a commercially available system, Diopsys® NOVA (Diopsys, Inc., Pine brook, NJ), version 2.19.19778.7332). The Flicker ERG will be consecutively recorded from both eyes by means of adhesive skin electrodes on the lower eyelid and skin. The stimulus will consist of white flashes flickering at 32 Hz over a white background as well as a sequence of 6 steps of increasing luminance.	Change from Baseline to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Macular pigment optical density (MPOD in relative density units)	Subjects are asked to identify when they detect a flickering stimulus of varying intensity, allowing determination of relative density of xanthophyll macular pigments.	Change from Baseline to 6 months
Optical coherence tomography angiography (OCTA): radial macular and optic nerve capillary density (number/square millimeter)	OCT angiography measurements will be performed using the Angiovue OCT by Optovue CA. It is a camera system that utilizes interferometry to measure the thickness and vascular profile of the macula and the optic nerve, allowing measurement of radial capillary count in both macula and the peripapillary optic nerve head region	Change from Baseline to 6 months

Collaborators and Investigators

• Sponsor: ZeaVision, LLC
• Collaborators: Western University of Health Sciences; Northeastern State University; Diopsys, Inc.
• Investigators: Study Chair: Nathan Lighthizer, OD, Northeastern State University, School of Optometry; Principal Investigator: Pinakin Davey, OD, PhD, Western University of Health Sciences, College of Optometry

Publications and helpful links

General Publications

• Chous AP, Richer SP, Gerson JD, Kowluru RA. The Diabetes Visual Function Supplement Study (DiVFuSS). Br J Ophthalmol. 2016 Feb;100(2):227-34. doi: 10.1136/bjophthalmol-2014-306534. Epub 2015 Jun 18.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2019
• Primary Completion (ANTICIPATED): December 1, 2021
• Study Completion (ANTICIPATED): December 1, 2022

Study Registration Dates

• First Submitted: October 1, 2019
• First Submitted That Met QC Criteria: October 3, 2019
• First Posted (ACTUAL): October 7, 2019

Study Record Updates

• Last Update Posted (ACTUAL): April 23, 2021
• Last Update Submitted That Met QC Criteria: April 21, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Endocrine System Diseases; Diabetic Angiopathies; Diabetes Complications; Diabetes Mellitus; Retinal Diseases; Diabetic Retinopathy
• Other Study ID Numbers: 19-094

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: anonymized data for statistical analysis only

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No