KeratoconusPhase 2/3NCT00841386
Treatment of Keratoconus Using Collagen Cross-Linking
A Phase 2/3 study testing Riboflavin-5-phosphate in people with Keratoconus, run by University at Buffalo at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Keratoconus
- What is being tested?
- Riboflavin-5-phosphate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2008to Dec 2011
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 35 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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
Show all 10Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites, 2 recruiting
- Recruiting
Fichte,Endl, & Elmer EyeCare
Amherst, New York, 14228
Linda Grant, C.O.M.T., 716-564-2020, linda.grant@fichte.com
Michael Endl, M.D., 716-564-2020, mpderme@aol.com
- Recruiting
The Ira G. Ross Eye Institute
Buffalo, New York, 14209
James J Reidy, M.D., 716-881-7920, jreidymd@mac.com
James J Reidy, M.D.
About this study
Official title: Treatment of Keratoconus Using Collagen Cross-Linking By Means of Topical Riboflavin and UV Light.
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. .
Read the 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.
- Conditions
- Keratoconus
- Being tested
- Riboflavin-5-phosphate, Sham cross-linking
- Keywords
- Cornea, Keratoconus, Ectasia, Riboflavin, Collagen cross-linking
- Medical subject headings
- Keratoconus, Corneal Diseases, Dilatation, Pathologic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Riboflavin-5-phosphateDrug
Also called Ricrolin (SOOFT Italia Inc.)
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.
Sham cross-linkingDrug
Also called Goniosol
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.
| Study group | Role | What they receive |
|---|---|---|
| Cross-linking treatment | Experimental | 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. Receives: Drug: Riboflavin-5-phosphate |
| Sham treatment group | Sham comparator | 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. Receives: Drug: Sham cross-linking |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best corrected visual acuity
Measured: 24 months
Spherical equivalent power of the cornea (Best spectacle refraction)
Measured: 24 months
KMax: the maximum corneal curvature
Measured: 24 months
Average corneal power of the cornea in the central 4 mm.
Measured: 24 months
Secondary outcomes (4)
Corneal resistance factor.
Measured: 24 months
Maximal posterior surface elevation of the cornea.
Measured: 24 months
Apical corneal thickness.
Measured: 24 months
Endothelial count.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2009 (estimated)
- Study startSep 2008
- Primary completionDec 2011 (estimated)
- Study completionDec 2011 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for KeratoconusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University at Buffalo
- Sponsor type
- University, hospital or other
- Investigators
- James J Reidy, M.D., Principal investigator, SUNY at Buffalo School of Medicine & Biomedical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00841386
- Sponsor's protocol ID
- 101365
- Status last verified
- Jan 2009
- First submitted
- 10 Feb 2009
- Last updated
- 11 Feb 2009
- Results posted
- No
- Data monitoring committee
- No
Publications
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. doi: 10.1016/j.jcrs.2007.04.047. No abstract available.
PubMed 17720054Mazzotta 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. doi: 10.1097/ICO.0b013e318030df5a.
PubMed 17457184Spoerl 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. doi: 10.1097/ICO.0b013e3180334f78.
PubMed 17457183Mazzotta 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. doi: 10.1177/112067210601600405.
PubMed 16952090Wollensak G. Crosslinking treatment of progressive keratoconus: new hope. Curr Opin Ophthalmol. 2006 Aug;17(4):356-60. doi: 10.1097/01.icu.0000233954.86723.25.
PubMed 16900027Caporossi 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. doi: 10.1016/j.jcrs.2006.01.091.
PubMed 16765803Kohlhaas 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. doi: 10.1016/j.jcrs.2005.12.092.
PubMed 16565005Wollensak 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. doi: 10.1016/s0002-9394(02)02220-1.
PubMed 12719068Mencucci 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. doi: 10.1016/j.jcrs.2007.03.021.
PubMed 17531694
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Keratoconus Using Collagen Cross-Linking By Means of Topical Riboflavin and UV Light.
- ClinicalTrials.gov ID
- NCT00841386
- Acronym / sponsor ID
- 101365
- Conditions
- Keratoconus
- Keywords
- Cornea, Keratoconus, Ectasia, Riboflavin, Collagen cross-linking
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- University at BuffaloUniversity, hospital or other
- Study start
- Sep 2008
- Primary completion
- Dec 2011 (estimated)
- Study completion
- Dec 2011 (estimated)
- First posted
- 11 Feb 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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. .
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cross-linking treatment | Experimental | Drug: Riboflavin-5-phosphateTopical 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. |
| Sham treatment group | Sham comparator | Drug: Sham cross-linkingTopical 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. |
Who may qualify
- Ages
- 16 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- 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:
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Riboflavin-5-phosphateAlso: Ricrolin (SOOFT Italia Inc.)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. | Drug | Cross-linking treatment |
| Sham cross-linkingAlso: GoniosolTopical 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. | Drug | Sham treatment group |
Primary outcome
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
4 secondary outcomes
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2009.
- Results publication: PubMed 17720054Natarajan 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. doi: 10.1016/j.jcrs.2007.04.047. No abstract available.
- Results publication: PubMed 17457184Mazzotta 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. doi: 10.1097/ICO.0b013e318030df5a.
- Results publication: PubMed 17457183Spoerl 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. doi: 10.1097/ICO.0b013e3180334f78.
- Results publication: PubMed 16952090Mazzotta 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. doi: 10.1177/112067210601600405.
- Results publication: PubMed 16900027Wollensak G. Crosslinking treatment of progressive keratoconus: new hope. Curr Opin Ophthalmol. 2006 Aug;17(4):356-60. doi: 10.1097/01.icu.0000233954.86723.25.
- Results publication: PubMed 16765803Caporossi 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. doi: 10.1016/j.jcrs.2006.01.091.
- Results publication: PubMed 16565005Kohlhaas 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. doi: 10.1016/j.jcrs.2005.12.092.
- Results publication: PubMed 12719068Wollensak 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. doi: 10.1016/s0002-9394(02)02220-1.
- Results publication: PubMed 17531694Mencucci 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. doi: 10.1016/j.jcrs.2007.03.021.
- National Keratoconus FoundationLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James J Reidy, M.D. principal investigator
SUNY at Buffalo School of Medicine & Biomedical Sciences
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Riboflavin-5-phosphate in people with Keratoconus, run by University at Buffalo at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 11 Feb 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact James J. Reidy, M.D. (716-881-7920, jreidymd@mac.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Best corrected visual acuity (time frame: 24 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00841386, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2009.