The Role of Antioxidant Supplementation in Keratoconus Patients

The Role of Antioxidants in Keratoconus Patients-A Randomized Controlled Trial of Oral Supplementation of Glutathione, Vitamin A, Vitamin C and Vitamin E

Keratoconus is the most common primary cornea ectasia, where the cornea undergoes structural changes, leading to loss of tissue integrity and vision loss. The prevalence of Keratoconus is 1:2000 in the general population. Oxidative stress has been thought to have a major effect in the disease pathogenesis of Keratoconus. In vitro studies have shown increase in metabolites related to oxidative stress in Keratoconus disease, and that Keratoconus cells undergo increased oxidative stress and tissue damage. Animal models have shown a therapeutic effect of Vitamin C (ascorbate) in corneal wound healing. Glutathione and Vitamins A, C, and E are important antioxidants in the human body. To this date, the role of systemic antioxidant supplementation in Keratoconus patients has yet to be studied. In addition, it has yet to be established as to whether there is a correlation between serum antioxidant levels, and the severity of disease in the Keratoconus patient. The investigators propose to investigate the plasma levels of antioxidants in relation to disease severity. The investigators will also investigate the role of antioxidant supplementation-consisting of parenteral Glutathione (GSH), and Vitamins A, C and E-in delaying the disease progression in Keratoconus.

Study Overview

• Status: Withdrawn
• Conditions: Keratoconus
• Intervention / Treatment: Other: Placebo; Combination product: Dietary Sources; Other: Antioxidants (Vitamins A,C,E) plus GSH; Dietary supplement: Centrum

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Palm Beach Gardens, Florida, United States, 33418
      • Bascom Palmer Eye Institute-- Palm Beach Gardens

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants would be without illness or condition that could make follow-up, or compliance with study medication difficult.
• Participants may have a prior diagnosis of Keratoconus, or may be diagnosed at the initial visit.
• Participants should not have an eye diagnosis, other than Keratoconus, that could adversely influence the visual acuity.
• These participants must not have had prior surgical procedure to treat Keratoconus, including collagen cross-linking, Intacs ring segments, or corneal transplantation.

Exclusion Criteria:

• would exclude smokers and former-smokers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo with Dietary Sources of Vitamins; Persons assigned to placebo, who obtain Vitamins A, C, E and Glutathione from dietary sources alone, and have not been on oral RDA supplementation, in the 1 month leading up the time of enrollment and throughout the study period.	Other: Placebo; Placebo pill; Combination product: Dietary Sources; From dietary sources of vitamins.
Active Comparator: Antioxidants(Vitamins A,C,E) plus GSH, plus Centrum; Persons assigned to the study medication, and are continuing the take an oral RDA supplementation, in the form of Centrum.	Other: Antioxidants (Vitamins A,C,E) plus GSH; Study medication would contain 500 milligrams of vitamin C, 400 International Units of vitamin E, and 15 milligrams of beta-carotene (the equivalent to 25,000 International Units of vitamin A).The study medication would also contain 1000mg of Glutathione (GSH).; Dietary supplement: Centrum; Centrum
Active Comparator: Antioxidants (Vitamins A,C, E) plus GSH; Persons assigned to the study medication alone, without oral RDA supplementation in the 1 month leading up the time of enrollment and throughout the study period.	Other: Antioxidants (Vitamins A,C,E) plus GSH; Study medication would contain 500 milligrams of vitamin C, 400 International Units of vitamin E, and 15 milligrams of beta-carotene (the equivalent to 25,000 International Units of vitamin A).The study medication would also contain 1000mg of Glutathione (GSH).
Active Comparator: Placebo plus Centrum; Persons assigned to placebo, who have been on oral RDA supplementation, who would continue to do so throughout the study.	Other: Placebo; Placebo pill; Dietary supplement: Centrum; Centrum

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Visual Acuity Measured by Snellen Chart	Baseline to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cornea thickness as measured by video keratography		Baseline to 24 months
Plasma level of Vitamin A	Blood draws to look at plasma level of Vitamin A	Baseline to 24 months
Plasma level of Vitamin C	Blood draws to look at plasma level of Vitamin C	Baseline to 24 months
Plasma level of Vitamin E	Blood draws to look at plasma level of Vitamin E	Baseline to 24 months
Plasma level of Glutathione (GSH)	Blood draws to look at plasma level of GSH	Baseline to 24 months

Collaborators and Investigators

• Sponsor: University of Miami
• Collaborators: Fight for Sight
• Investigators: Principal Investigator: Ellen Koo, M.D., University of Miami

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2021
• Primary Completion (Anticipated): July 1, 2022
• Study Completion (Anticipated): March 1, 2023

Study Registration Dates

• First Submitted: February 25, 2016
• First Submitted That Met QC Criteria: July 7, 2016
• First Posted (Estimate): July 11, 2016

Study Record Updates

• Last Update Posted (Actual): August 16, 2021
• Last Update Submitted That Met QC Criteria: August 11, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Keratoconus progression; Vitamins and keratoconus; Vitamin supplementation
• Additional Relevant MeSH Terms: Eye Diseases; Corneal Diseases; Keratoconus; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Vitamin A
• Other Study ID Numbers: 20150646

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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