Treatment of Keratoconus Using Collagen Cross-Linking

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ClinicalTrials.gov Identifier: NCT00841386

Recruitment Status : Unknown

Verified January 2009 by University at Buffalo.
Recruitment status was: Recruiting

First Posted : February 11, 2009

Last Update Posted : February 11, 2009

Sponsor:

Information provided by:

University at Buffalo

Study Description

Brief Summary:

The purpose of this study is to determine the effectiveness of collagen cross-linking in the cornea in halting the progression and possibly partially reversing the effects of keratoconus. Keratoconus is a progressive weakening in the cornea that causes irregular astigmatism and thinning of the cornea. The overall effect is reduction of vision, and in more advanced cases, scarring of the cornea that may lead to the need for corneal transplantation. Cross-linking has been shown increase the rigidity of the cornea. The patients would be treated once and then followed over 24 months. .

Condition or disease	Intervention/treatment	Phase
Keratoconus	Drug: Riboflavin-5-phosphate Drug: Sham cross-linking	Phase 2 Phase 3

Detailed Description:

The goal is for two groups of approximately 66 patients to be included in the study. One eye from the first group will undergo treatment, while the second group of age matched individuals will serve as a control. It will be a prospective, randomized, blinded study. Each patient will be randomized at the beginning of enrollment in the study and will receive a randomization number. The following parameters will be followed: 1. Best corrected spectacle acuity (BCSA) 2. The steepest keratometry measurement (KMax) as measured by computerized corneal topography 3. Apical corneal thickness 4. Corneal mechanical resistance. These measurements will be repeated at 1 month, 3 months, 6 months, 12, 18, and 24 months following treatment.

Study Design


Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	150 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Treatment of Keratoconus Using Collagen Cross-Linking By Means of Topical Riboflavin and UV Light.
Study Start Date :	September 2008
Estimated Primary Completion Date :	December 2011
Estimated Study Completion Date :	December 2011

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Keratoconus

MedlinePlus related topics: Corneal Disorders

Drug Information available for: Riboflavin Riboflavin sodium phosphate Riboflavin 5'-phosphate sodium Collagen

Genetic and Rare Diseases Information Center resources: Keratoconus

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cross-linking treatment Topical anesthesia (lidocaine jelly 2%) will be used. The central 9 mm of corneal epithelium will be removed cautiously with an Amoils brush. Riboflavin 0.1% solution will be applied (10 mg riboflavin-5-phosphate in 10 ml dextran T-500 20% solution, supplied in a sterile, single dose container) to the cornea every 2-3 minutes for 15 minutes and then every 5 minutes thereafter. The UV source will be from the CBM VEGA X-linker (CSO, Florence, Italy). A wavelength of 370 nm will be used to direct 5.4 J/cm2 to the area of cornea debrided for 30 minutes. The distance from the UV source to the cornea will be 1.5 to 5.4 cm.	Drug: Riboflavin-5-phosphate Riboflavin 0.1% (10 mg riboflavin-5-phosphate in 10 ml dextran T-500 20% solution, supplied in a sterile, single dose container) will be applied to the cornea every 2-3 minutes for 15 minutes prior to starting UV irradiation. The UV irradiation will be given in six 5 minute intervals. Additional riboflavin will be administered following each 5 minute UV treatment. Other Name: Ricrolin (SOOFT Italia Inc.)
Sham Comparator: Sham treatment group Topical anesthesia (lidocaine jelly 2%) will be used. Differing from the treatment group, no epithelium will be debrided, but instead, this step will be skipped and a 2% methylcellulose solution combined with 1% fluorescein dye will be applied to the cornea every 5 minutes for 30 minutes. The patient will be placed under the UV device, but instead of the UV light, the LED aiming beam will be applied for 30 minutes.	Drug: Sham cross-linking Topical anesthesia (lidocaine jelly 2%) will be used. Differing from the treatment group, no epithelium will be debrided, but instead, this step will be skipped and 2% methylcellulose solution with 1% sodium fluorescein will be applied to the cornea every 5 minutes for 15 minutes, and then every 5 minutes during the sham UV treatment. The patient will be placed under the UV device, and the aiming beam applied. Other Name: Goniosol

Arm

Intervention/treatment

Experimental: Cross-linking treatment

Topical anesthesia (lidocaine jelly 2%) will be used. The central 9 mm of corneal epithelium will be removed cautiously with an Amoils brush. Riboflavin 0.1% solution will be applied (10 mg riboflavin-5-phosphate in 10 ml dextran T-500 20% solution, supplied in a sterile, single dose container) to the cornea every 2-3 minutes for 15 minutes and then every 5 minutes thereafter. The UV source will be from the CBM VEGA X-linker (CSO, Florence, Italy). A wavelength of 370 nm will be used to direct 5.4 J/cm2 to the area of cornea debrided for 30 minutes. The distance from the UV source to the cornea will be 1.5 to 5.4 cm.

Drug: Riboflavin-5-phosphate

Riboflavin 0.1% (10 mg riboflavin-5-phosphate in 10 ml dextran T-500 20% solution, supplied in a sterile, single dose container) will be applied to the cornea every 2-3 minutes for 15 minutes prior to starting UV irradiation. The UV irradiation will be given in six 5 minute intervals. Additional riboflavin will be administered following each 5 minute UV treatment.

Other Name: Ricrolin (SOOFT Italia Inc.)

Sham Comparator: Sham treatment group

Topical anesthesia (lidocaine jelly 2%) will be used. Differing from the treatment group, no epithelium will be debrided, but instead, this step will be skipped and a 2% methylcellulose solution combined with 1% fluorescein dye will be applied to the cornea every 5 minutes for 30 minutes. The patient will be placed under the UV device, but instead of the UV light, the LED aiming beam will be applied for 30 minutes.

Drug: Sham cross-linking

Topical anesthesia (lidocaine jelly 2%) will be used. Differing from the treatment group, no epithelium will be debrided, but instead, this step will be skipped and 2% methylcellulose solution with 1% sodium fluorescein will be applied to the cornea every 5 minutes for 15 minutes, and then every 5 minutes during the sham UV treatment. The patient will be placed under the UV device, and the aiming beam applied.

Other Name: Goniosol

Outcome Measures

Primary Outcome Measures :

Best corrected visual acuity [ Time Frame: 24 months ]
Spherical equivalent power of the cornea (Best spectacle refraction) [ Time Frame: 24 months ]
KMax: the maximum corneal curvature [ Time Frame: 24 months ]
Average corneal power of the cornea in the central 4 mm. [ Time Frame: 24 months ]

Secondary Outcome Measures :

Corneal resistance factor. [ Time Frame: 24 months ]
Maximal posterior surface elevation of the cornea. [ Time Frame: 24 months ]
Apical corneal thickness. [ Time Frame: 24 months ]
Endothelial count. [ Time Frame: 24 months ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	16 Years to 35 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

no prior history of ocular surgery
treatment eye must have a maximum corneal power of between 47 D and 60 diopters
corneal thickness must be greater than 400 µ
absence of corneal scarring
patients must meet the diagnostic criteria for keratoconus, which include one or more of the following features:
- high myopia
- corneal ectasia as viewed by slit-lamp exam or measured by pachometry
- Vogt's striae
- topographic findings of superior flattening and inferior steepening of the cornea
- presence of Fleischer ring

Exclusion Criteria:

history of prior ocular surgery (history of contact lens use is not an exclusion criterion)
average corneal power > 60 D
presence of corneal scarring
corneal thickness 400 µ or less
history of herpes simplex virus keratitis
history of uveitis
pre-existing glaucoma

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00841386

Contacts


Contact: James J. Reidy, M.D.	716-881-7920	jreidymd@mac.com
Contact: Jeanne Stutz	716-881-7920	jstutz@buffalo.edu

Locations


United States, New York
Fichte,Endl, & Elmer EyeCare	Recruiting
Amherst, New York, United States, 14228
Contact: Linda Grant, C.O.M.T. 716-564-2020 linda.grant@fichte.com
Contact: Michael Endl, M.D. 716-564-2020 mpderme@aol.com
Principal Investigator: Michael Endl, M.D.
Sub-Investigator: Thomas R Elmer, M.D.
The Ira G. Ross Eye Institute	Recruiting
Buffalo, New York, United States, 14209
Contact: James J Reidy, M.D. 716-881-7920 jreidymd@mac.com
Principal Investigator: James J Reidy, M.D.
Sub-Investigator: Sandra L Everett, M.D.

Sponsors and Collaborators

University at Buffalo

Investigators


Principal Investigator:	James J Reidy, M.D.	SUNY at Buffalo School of Medicine & Biomedical Sciences

More Information

Additional Information:

National Keratoconus Foundation This link exits the ClinicalTrials.gov site

Publications of Results:

Natarajan R, Padmanabhan P, Guruswami S. Hydration behavior of porcine cornea crosslinked with riboflavin and ultraviolet A. J Cataract Refract Surg. 2007 Sep;33(9):1503.

Mazzotta C, Balestrazzi A, Traversi C, Baiocchi S, Caporossi T, Tommasi C, Caporossi A. Treatment of progressive keratoconus by riboflavin-UVA-induced cross-linking of corneal collagen: ultrastructural analysis by Heidelberg Retinal Tomograph II in vivo confocal microscopy in humans. Cornea. 2007 May;26(4):390-7.

Spoerl E, Mrochen M, Sliney D, Trokel S, Seiler T. Safety of UVA-riboflavin cross-linking of the cornea. Cornea. 2007 May;26(4):385-9. Review.

Mazzotta C, Traversi C, Baiocchi S, Sergio P, Caporossi T, Caporossi A. Conservative treatment of keratoconus by riboflavin-uva-induced cross-linking of corneal collagen: qualitative investigation. Eur J Ophthalmol. 2006 Jul-Aug;16(4):530-5.

Wollensak G. Crosslinking treatment of progressive keratoconus: new hope. Curr Opin Ophthalmol. 2006 Aug;17(4):356-60. Review.

Caporossi A, Baiocchi S, Mazzotta C, Traversi C, Caporossi T. Parasurgical therapy for keratoconus by riboflavin-ultraviolet type A rays induced cross-linking of corneal collagen: preliminary refractive results in an Italian study. J Cataract Refract Surg. 2006 May;32(5):837-45.

Kohlhaas M, Spoerl E, Schilde T, Unger G, Wittig C, Pillunat LE. Biomechanical evidence of the distribution of cross-links in corneas treated with riboflavin and ultraviolet A light. J Cataract Refract Surg. 2006 Feb;32(2):279-83.

Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003 May;135(5):620-7.

Mencucci R, Mazzotta C, Rossi F, Ponchietti C, Pini R, Baiocchi S, Caporossi A, Menchini U. Riboflavin and ultraviolet A collagen crosslinking: in vivo thermographic analysis of the corneal surface. J Cataract Refract Surg. 2007 Jun;33(6):1005-8.


Responsible Party:	James J. Reidy, M.D., Department of Ophthalmology, SUNY at Buffalo
ClinicalTrials.gov Identifier:	NCT00841386 History of Changes
Other Study ID Numbers:	101365
First Posted:	February 11, 2009 Key Record Dates
Last Update Posted:	February 11, 2009
Last Verified:	January 2009

Keywords provided by University at Buffalo:


Cornea Keratoconus Ectasia Riboflavin Collagen cross-linking

Additional relevant MeSH terms:


Keratoconus Corneal Diseases Eye Diseases Pharmaceutical Solutions Lidocaine Riboflavin Flavin Mononucleotide Anesthetics, Local Anesthetics Central Nervous System Depressants Physiological Effects of Drugs Sensory System Agents	Peripheral Nervous System Agents Anti-Arrhythmia Agents Voltage-Gated Sodium Channel Blockers Sodium Channel Blockers Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action Vitamin B Complex Vitamins Micronutrients Growth Substances Photosensitizing Agents Dermatologic Agents

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