KeratoconusPhase 3NCT01464268
Transepithelial Corneal Collagen Crosslinking for Keratoconus and Corneal Ectasia
A Phase 3 study testing Riboflavin in people with Keratoconus and Corneal Ectasia, run by Cornea and Laser Eye Institute at 1 site in United States.
Trial summary
Corneal collagen crosslinking (CXL) has been proposed as an effective method of reducing progression of both keratoconus and corneal ectasia after surgery, as well as possibly decreasing the steepness of the cornea in these pathologies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Keratoconus, Corneal Ectasia
- What is being tested?
- Riboflavin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2011to Dec 2025
- Phase
- Phase 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 years of age or older
- A diagnosis of keratoconus or a diagnosis of corneal ectasia after corneal refractive surgery
- Vision with contact lenses or glasses is worse than 20/20
- Corneal thickness greater than 375 microns at the thinnest point
Who cannot join
- Eyes classified as either normal, atypical normal, or keratoconus suspect on the severity grading scheme.
- Corneal pachymetry ≤ 350 microns at the thinnest point measured by Pentacam in the eye(s) to be treated.
- Previous ocular condition (other than refractive error) in the eye(s) to be treated that may predispose the eye for future complications
- Clinically significant corneal scarring in the CXL treatment zone
- Pregnancy (including plan to become pregnant) or lactation during the course of the study
- A known sensitivity to study medications
- Patients with nystagmus or any other condition that would prevent a steady gaze during the CXL treatment or other diagnostic tests.
- Patients with a current condition that, in the investigator's opinion, would interfere with or prolong epithelial healing.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cornea and Laser Eye Institute
Teaneck, New Jersey, 07666
About this study
Corneal collagen crosslinking (CXL) has been proposed as an effective method of reducing progression of both keratoconus and corneal ectasia after surgery, as well as possibly decreasing the steepness of the cornea in these pathologies. During previous studies of the CXL procedure, the surface epithelial cells have been removed. Transepithelial crosslinking in which the epithelium is not removed has been proposed to offer a number of advantages over traditional crosslinking including an increased safety profile by reducing the risk for infection as no epithelial barrier will be broken, faster visual recovery and improved patient comfort in the early postoperative healing period.
Read the detailed description
The objective of this study is to investigate the difference between two regimens of transepithelial crosslinking. The study will compare two riboflavin dosing regimens during the crosslinking procedure. The primary objective of this study is to evaluate the safety and efficacy of transepithelial corneal collagen crosslinking performed with riboflavin 0.1% for reducing corneal curvature. Safety and efficacy outcomes will then be compared between the treatment groups. In particular, we will compare the two groups with regard to their efficacy in reducing corneal curvature. Secondary outcomes will include visual acuity. Safety assessments will include a tabulation of adverse events, patient symptoms, loss of visual acuity, changes in endothelial cell density, slit lamp examination of the cornea and lens, and contact lens tolerance for contact lens wearers
- Conditions
- Keratoconus, Corneal Ectasia
- Being tested
- Riboflavin
- Keywords
- Keratoconus, Corneal Ectasia, Collagen Crosslinking, Riboflavin
- Medical subject headings
- Keratoconus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RiboflavinDrug
Also called Riboflavin without dextran
Administration of riboflavin every 2 minutes for the duration of UV exposure.
RiboflavinDrug
Also called Riboflavin without Dextran
Administration of riboflavin every 1 minute for the duration of UV exposure.
| Study group | Role | What they receive |
|---|---|---|
| Riboflavin drops every minute | Active comparator | Administration of riboflavin every 2 minutes for the duration of UV exposure. Receives: Drug: Riboflavin |
| Riboflavin drops every 2 minutes | Active comparator | Administration of riboflavin every 1 minute for the duration of UV exposure. Receives: Drug: Riboflavin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Keratometry
The change in maximum keratometry (Kmax) from baseline will be evaluated at 12 months for all eyes randomized to the two treatment groups. As a secondary analysis of this endpoint, the change in maximum keratometry (Kmax) from baseline will be evaluated at 1, 3 and 6 month for all eyes
Measured: 12 months
Secondary outcomes (3)
Manifest refraction
The change in manifest refraction spherical equivalent from baseline will be evaluated at 12 months. As a secondary analysis of this endpoint, a repeated measures analysis of variance will be conducted to assess the profile of the treatments across time at 1,3, and 6 months to look at the effect of wound healing on this variable.
Measured: 12 months
Visual Acuity
Change in BSCVA (best spectacle corrected visual acuity) and UCVA (uncorrected visual acuity) compared to the baseline examination will be evaluated at 12 months postoperatively. As a secondary analysis of this endpoint, data across time from 1, 3, and 6 months following the CXL procedure will be analyzed.
Measured: 12 months
Endothelial cell density
Endothelial cell count will be obtained using specular microscopy (Konan Medical) prior to CXL treatment and at 12 months postoperatively.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2011 (estimated)
- Study startNov 2011
- Primary completionDec 2024 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cornea and Laser Eye Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Peter Hersh, MD, Principal investigator, Cornea and Laser Eye Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01464268
- Sponsor's protocol ID
- CLEI-EpiCXL
- Status last verified
- Feb 2023
- First submitted
- 1 Nov 2011
- Last updated
- 8 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
Publications
Hersh PS, Greenstein SA, Fry KL. Corneal collagen crosslinking for keratoconus and corneal ectasia: One-year results. J Cataract Refract Surg. 2011 Jan;37(1):149-60. doi: 10.1016/j.jcrs.2010.07.030.
PubMed 21183110Davis SA, Bovelle R, Han G, Kwagyan J. Corneal collagen cross-linking for bacterial infectious keratitis. Cochrane Database Syst Rev. 2020 Jun 17;6(6):CD013001. doi: 10.1002/14651858.CD013001.pub2.
PubMed 32557558
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transepithelial Corneal Collagen Crosslinking for Keratoconus and Corneal Ectasia
- ClinicalTrials.gov ID
- NCT01464268
- Acronym / sponsor ID
- CLEI-EpiCXL
- Conditions
- Keratoconus, Corneal Ectasia
- Keywords
- Keratoconus, Corneal Ectasia, Collagen Crosslinking, Riboflavin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- Cornea and Laser Eye InstituteUniversity, hospital or other
- Study start
- Nov 2011
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 3 Nov 2011 (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.
Corneal collagen crosslinking (CXL) has been proposed as an effective method of reducing progression of both keratoconus and corneal ectasia after surgery, as well as possibly decreasing the steepness of the cornea in these pathologies. During previous studies of the CXL procedure, the surface epithelial cells have been removed. Transepithelial crosslinking in which the epithelium is not removed has been proposed to offer a number of advantages over traditional crosslinking including an increased safety profile by reducing the risk for infection as no epithelial barrier will be broken, faster visual recovery and improved patient comfort in the early postoperative healing period.
Detailed description
The objective of this study is to investigate the difference between two regimens of transepithelial crosslinking. The study will compare two riboflavin dosing regimens during the crosslinking procedure. The primary objective of this study is to evaluate the safety and efficacy of transepithelial corneal collagen crosslinking performed with riboflavin 0.1% for reducing corneal curvature. Safety and efficacy outcomes will then be compared between the treatment groups. In particular, we will compare the two groups with regard to their efficacy in reducing corneal curvature. Secondary outcomes will include visual acuity. Safety assessments will include a tabulation of adverse events, patient symptoms, loss of visual acuity, changes in endothelial cell density, slit lamp examination of the cornea and lens, and contact lens tolerance for contact lens wearers
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Riboflavin drops every minute | Active comparator | Drug: RiboflavinAdministration of riboflavin every 2 minutes for the duration of UV exposure. |
| Riboflavin drops every 2 minutes | Active comparator | Drug: RiboflavinAdministration of riboflavin every 1 minute for the duration of UV exposure. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 18 years of age or older
- A diagnosis of keratoconus or a diagnosis of corneal ectasia after corneal refractive surgery
- Vision with contact lenses or glasses is worse than 20/20
- Corneal thickness greater than 375 microns at the thinnest point
Key exclusion criteria (8 listed)
- Eyes classified as either normal, atypical normal, or keratoconus suspect on the severity grading scheme.
- Corneal pachymetry ≤ 350 microns at the thinnest point measured by Pentacam in the eye(s) to be treated.
- Previous ocular condition (other than refractive error) in the eye(s) to be treated that may predispose the eye for future complications
- Clinically significant corneal scarring in the CXL treatment zone
- Pregnancy (including plan to become pregnant) or lactation during the course of the study
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 |
|---|---|---|
| RiboflavinAlso: Riboflavin without dextranAdministration of riboflavin every 2 minutes for the duration of UV exposure. | Drug | Riboflavin drops every 2 minutes |
| RiboflavinAlso: Riboflavin without DextranAdministration of riboflavin every 1 minute for the duration of UV exposure. | Drug | Riboflavin drops every minute |
Primary outcome
Maximum Keratometry
Time frame: 12 months
The change in maximum keratometry (Kmax) from baseline will be evaluated at 12 months for all eyes randomized to the two treatment groups. As a secondary analysis of this endpoint, the change in maximum keratometry (Kmax) from baseline will be evaluated at 1, 3 and 6 month for all eyes
3 secondary outcomes
Manifest refraction
Time frame: 12 months
Visual Acuity
Time frame: 12 months
Endothelial cell density
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2023.
- Background: PubMed 21183110Hersh PS, Greenstein SA, Fry KL. Corneal collagen crosslinking for keratoconus and corneal ectasia: One-year results. J Cataract Refract Surg. 2011 Jan;37(1):149-60. doi: 10.1016/j.jcrs.2010.07.030.
- Derived from this study: PubMed 32557558Davis SA, Bovelle R, Han G, Kwagyan J. Corneal collagen cross-linking for bacterial infectious keratitis. Cochrane Database Syst Rev. 2020 Jun 17;6(6):CD013001. doi: 10.1002/14651858.CD013001.pub2.
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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.
Peter Hersh, MD principal investigator
Cornea and Laser Eye Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Riboflavin in people with Keratoconus and Corneal Ectasia, run by Cornea and Laser Eye Institute at 1 site 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 4 inclusion and 8 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 8 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Keratometry (time frame: 12 months). 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 NCT01464268, which also lists 2 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 8 Feb 2023.