Dietary Riboflavin (Vitamin B-2) and Cornea Cross-Linking

• ClinicalTrials.gov Identifier: NCT03095235
• Recruitment Status: Recruiting
• First Posted: March 29, 2017
• Last Update Posted: April 22, 2019
• Sponsor: University of Missouri-Columbia
• Information provided by (Responsible Party): John Jarstad, M.D., University of Missouri-Columbia

Study Description

Brief Summary:

Corneal ectasia is characterized by irregularity and thinning of the cornea, causing the cornea to bulge forward and cause distorted vision and impaired visual acuity. Corneal ectasia is a complication after refractive (LASIK) surgery. It is also the primary problem in keratoconus, a gradually progressive inherited condition that typically is manifested in young adulthood, more commonly in women. Treatment approaches to stabilize the cornea's shape include rigid contact lenses, surgical implantation of stiff plastic intrastromal corneal ring segments, a collagen cross-linking procedure and, in severe cases, cornea transplantation. The collagen cross-linking procedure involves topical application of a concentrated riboflavin (vitamin B2) solution after the corneal epithelium is scraped, followed by ultraviolet (UV) light exposure. UV light stimulates riboflavin to form new bonds (cross links) between the cornea's connective tissue, giving the cornea additional strength to maintain its shape and prevent the need for transplantation. The cost of one treatment using this system is $2,500 to $3,500. A small prospective study including 7 patients with keratoconus was started on a trial of oral riboflavin and 15 minutes of natural sunlight exposure daily. These patients reported no adverse effects and preliminary results showed corneal stabilization and/or corneal flattening in all 7 patients It is hypothesized that dietary riboflavin and natural sunlight is as effective in corneal crosslinking as the currently FDA approved Avedro therapy. If the clinical study confirms the investigators' early observations of the benefits of this approach, coupled with animal studies that document corneal cross-linking, the investigators will have data to pursue funding for larger clinical and animal studies. This has the potential to save millions of dollars in health care costs and ease the burden of treatment in patients who require therapy to induce corneal cross-linking to stabilize the cornea's shape.

Condition or disease	Intervention/treatment	Phase
Keratoconus; Cornea Ectasia	Dietary Supplement: Dietary riboflavin	Not Applicable

Detailed Description:

Corneal ectasia as a complication from refractive (LASIK) surgery as well as keratoconus is a slowly progressive condition that results in high patient morbidity. Treatment options aim to stabilize the shape of the cornea using rigid contact lenses, surgical insertion of stiff plastic intrastromal rings, corneal cross linking, and ultimately corneal transplant in severe patients. The recently FDA approved "Dresden Protocol" involves painful cornea scraping followed by application of concentrated Riboflavin, followed by immediate collagen cross linking with UV light exposure which results in shortening and thickening of the collagen fibrils, and therefore a stronger, stiffer cornea. Avedro has demonstrated an average cornea flattening (K max reduction) of 1.4 diopters and 1.7diopters in two different studies. The current cost of Avedro therapy is between $2500 -$3500 per treatment. This is considered experimental at this time and therefore is not covered by any insurance.To spare the patient the severe pain involved in the current procedure, and to avoid the high cost (Avedro is not covered by any medical insurance), the investigator started 7 patients with keratoconus from 2011-2015 in his private practice in Seattle on a trial of oral riboflavin (100 mg or 400 mg daily) and 15 minutes of sunlight exposure daily. No adverse effects have ever been reported with high-dose dietary riboflavin supplements. The results of this preliminary trial are remarkable. During follow-up from 6 months to 5 years, all 7 patients have had corneal stabilization and/or corneal flattening. One patient experienced flattening of the cornea by 1.5 Diopters, comparable to the best results of the Avedro system. A limited animal study is currently underway to document that corneal cross-linking occurs in response to dietary riboflavin and UV exposure from the sun. This clinical study would expand the promising preliminary findings to a larger sample size. This has the potential to save millions of dollars in health care costs and ease the burden of treatment in patients who require therapy to induce corneal cross-linking to stabilize the cornea's shape.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 24 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Dietary Riboflavin (Vitamin B-2) and Cornea Cross-Linking
• Actual Study Start Date: May 1, 2017
• Estimated Primary Completion Date: January 2022
• Estimated Study Completion Date: January 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment with riboflavin; Patients will take 400 mg dietary riboflavin per day and go outside without sunglasses for 15 minutes per day to evaluate the effects of riboflavin B2 and natural UV light from sun exposure on cornea cross linking and stabilization of ectatic disease.	Dietary Supplement: Dietary riboflavin; Dietary riboflavin is vitamin B2. It has been shown to be safe in children in the treatment of migraines at doses of 400 mg per day. There are no known documented side effects; Other Name: Vitamin B2

Outcome Measures

Primary Outcome Measures :

1. Degree of corneal steepening [ Time Frame: 6 months ]
   Keratometry measures the degree of astigmatism of the cornea to monitor the degree of cornea steepening

Secondary Outcome Measures :

1. Best corrected visual acuity [ Time Frame: 6 months ]
   Measures the best vision the patient is able to see at that time

Eligibility Criteria

• Ages Eligible for Study: 12 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• patients identified as having keratoconus or post refractive cornea ectasia with astigmatism of 1.5 Diopters or greater.

Exclusion Criteria:

• Known sensitivity to riboflavin, sunlight.
• patients on medications with side effects of increased sunlight sensitivity should discuss participation with their prescribing provider prior to participation

Contacts and Locations

Contacts

Contact: John S Jarstad, MD; (573) 884-2876; jarstadj@health.missouri.edu

Contact: Van D Nguyen, MD; (573) 884-2876; nguyenvd@health.missouri.edu

Locations

United States, Missouri

University of Missouri; Recruiting

Columbia, Missouri, United States, 65212

Contact: Lindsey M McDaniel, MD 573-882-1506

Contact: John Jarstad, MD 5738821506

Sponsors and Collaborators

University of Missouri-Columbia

Investigators

• Principal Investigator: John S Jarstad, MD; University of Missouri- Department of Ophthalmology

More Information

• Responsible Party: John Jarstad, M.D., Associate Professor, Department of Ophthalmology, University of Missouri-Columbia
• ClinicalTrials.gov Identifier: NCT03095235
• Other Study ID Numbers: 2006390
• First Posted: March 29, 2017
• Last Update Posted: April 22, 2019
• Last Verified: April 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by John Jarstad, M.D., University of Missouri-Columbia:

keratoconus; cornea ectasia

Additional relevant MeSH terms:

Keratoconus; Corneal Diseases; Dilatation, Pathologic; Eye Diseases; Pathological Conditions, Anatomical; Vitamins; Riboflavin; Vitamin B Complex; Micronutrients; Nutrients; Growth Substances; Physiological Effects of Drugs; Photosensitizing Agents; Dermatologic Agents