Corneal UlcersPhase 1NCT02068430
Safety and Effectiveness of the UV-X System for Corneal Collagen Cross-Linking in Eyes With Refractory Corneal Infection
A Phase 1 study testing Riboflavin 0.1% and UV-X™ Illumination System in people with Corneal Ulcers, run by Stephen Trokel at 1 site in United States.
Trial summary
This study will evaluate the Safety and Effectiveness of the UV-X System for Corneal Collagen Cross-Linking in Eyes with Corneal Infection. The treatment of UV-X system is to use the eyedrops of the riboflavin, also known as vitamin B2, and ultraviolet A (UVA) light. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Corneal Ulcers
- What is being tested?
- Riboflavin 0.1% and UV-X™ Illumination System
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2008to Dec 2015
- Phase
- Phase 1
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subjects who have one eye that meets the following criteria:
- 18 years of age or older
- Having a diagnosis of a corneal ulcer.
- Corneal scraping sent for cultures and sensitivities.
- Having been treated for at least three days with conventional broad spectrum anti infective therapy without improvement
- Showing no response to the therapy by one or more of the following criteria:
Show all 12Show fewer
- Progressive thinning of cornea
- Increasing diameter of corneal ulcer
- Increasing diameter of corneal infiltrate
- Persistent epithelial defect
- Persistent inflammatory signs as iritis and hypopyon
- Persistent pain
Who cannot join
- All subjects meeting any of the following criteria will be excluded from this study:
- A corneal ulcer that has perforated
- A corneal ulcer that has produced a descemetocele.
- Women who may be breast-feeding and pregnant women.
- Herpetic infection suggested by history or clinical evaluation.
Trial locations and contacts
1 site in 1 country.
United States1 site
Harkness Eye Institute Columbia University
New York, New York, 10035
About this study
This study will evaluate the Safety and Effectiveness of the UV-X System for Corneal Collagen Cross-Linking in Eyes with Corneal Infection. The treatment of UV-X system is to use the eyedrops of the riboflavin, also known as vitamin B2, and ultraviolet A (UVA) light. The eye drops are placed in affected eye and then affected cornea is exposed to UVA.
UVA/riboflavin corneal collagen cross-linking was first used to treat patients in 1998 in Dresden, Germany. Data to date obtained mostly by physicians outside the United States has strongly suggested this treatment as an acceptable alternative, and many subjects have had a lasting effect (no progression) 3-5 years after their initial treatment.
Read the detailed description
This study is designed to evaluate the safety and effectiveness of using the UV-X™ system for treating corneal ulcers that have proven refractory to conventional antibiotic treatment.
The UV-X™ system is a combination product consisting of a UVA 365 nm wavelength light source (UV-X™ Illumination System) and riboflavin (Medio-Cross® Riboflavin 0.1%) ophthalmic solution. The therapeutic effect is mediated by the photochemical interaction of the ultraviolet (UV) light with the riboflavin that has been saturated into the infected corneal stromal tissues.
The photochemical interaction of UVA light with riboflavin has been used to sterilize pathogens in blood and blood products. Pathogens including viruses, bacteria, fungi, and protozoa have shown to be sterilized using this photochemical process. Presumably singlet oxygen is produced by the interaction of the UVA with the riboflavin. It is this singlet oxygen that interacts with the pathogen's Deoxyribonucleic acid (DNA) in a sufficiently disruptive manner to render the exposed field sterile.
The cross-linking improves mechanical properties in the anterior stroma and has been shown to stabilize corneal structure in patients with progressive keratoconus and ectasias following refractive surgery. The same technology has been applied to a handful of patients with corneal ulcers and a single small series with bullous keratopathy. In no case was the patient worsened by this treatment. In the majority of the cases, considerable clinical reversal of a deteriorating clinical course was obtained. There has been debate about the mechanism of action of this beneficial effect. It has been speculated that a proteolytic collagenase enzyme was destroyed by the photochemical process. As an alternate, it has been suggested that the corneal collagen is strengthened by the cross linking and becomes more resistant to the infectious process. Finally a direct sterilization effect of the UVA light, the riboflavin, or the combination has been postulated. Recent laboratory work has shown that staphylococci cultures on an agar plate will be killed when exposed to the combination of UVA and riboflavin as used in these experiments. Neither the UVA nor the riboflavin alone had any bactericidal effect.
The procedure that has been used and that the investigators propose to study to treats corneal infections and ulcerations is identical to the procedure used to strengthen the cornea. It is performed by saturating the cornea with riboflavin 0.1% riboflavin solution and then exposing the riboflavin soaked cornea to UVA light. After the corneal stroma saturation is achieved, the infected tissues are exposed to UVA light at 365 nm and an irradiance of 3 mW/cm2 for 30 minutes. Exposure of the cornea to this combination of UVA light (365 nm; 3 mW/cm2 irradiation; 30 minutes duration) after topical administration of riboflavin appears to have a broad sterilization effect based on the photochemical interaction of the UVA and the riboflavin.
- Conditions
- Corneal Ulcers
- Being tested
- Riboflavin 0.1%, UV-X™ Illumination System
- Keywords
- Corneal Ulcers, cross-linking, UVA, Riboflavin
- Medical subject headings
- Corneal Ulcer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Riboflavin 0.1%Drug
Also called Riboflavin
After topical anesthesia, 1 drop of Riboflavin 0.1% ophthalmic solution will be instilled topically in the eye every 2 minutes for 30 minutes. At the end of the 30 minute riboflavin pre-treatment period, the eye will be examined with blue light for the presence of a yellow flare in the anterior chamber.
UV-X™ Illumination SystemOther
Also called UVA light
When the yellow flare in the anterior chamber is confirmed, the eye will be aligned under the UV-X™ light with the treatment plane at a working distance that is 50mm from the UV-X™ beam aperture. The correct aperture setting will be selected for the size of the eye (7.5 , 9.5, or 11 mm), and the eye will be irradiated for 30 minutes, during which time instillation of riboflavin will continue (1 drop every 2 minutes). At the end of 30 minutes, the UV light source will automatically switch to the off position. The operator will keep track of irradiation time independently to confirm the actual treatment time.
| Study group | Role | What they receive |
|---|---|---|
| Riboflavin 0.1% & UV-X™ Illumination System | Experimental | UV-X Cross linking: After topical anesthesia, 1 drop of Riboflavin 0.1% ophthalmic solution will be instilled topically in the eye every 2 minutes for 30 minutes. At the end of the 30 minute riboflavin pre-treatment period, the eye will be examined with blue light for the presence of a yellow flare in the anterior chamber. When the yellow flare in the anterior chamber is confirmed, the eye will be aligned under the UV-X™ light with the treatment plane at a working distance that is 50mm from the UV-X™ beam aperture. Receives: Drug: Riboflavin 0.1%; Other: UV-X™ Illumination System |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with healed corneal ulcers
Stabilization of the corneal ulcer: The endpoint will be the healing of the ulcer with re-epithelialization of its surface and stromal clearing. The patients will be followed on a daily basis until the ulcer has shown definite signs of resolution requiring a longer interval between exams or alternative therapeutic measures become necessary.
Measured: 6 months
Number of adverse events
The conditions to be treated are severe and have considerable functional loss. Vision loss, pain, corneal perforation, and blindness are often outcomes of severe progressive corneal ulcers. An abrupt worsening of the clinical appearance of the cornea or a worsening of symptoms will be considered as an adverse event.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2014 (estimated)
- Study startNov 2008
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Corneal UlcersStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stephen Trokel
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Stephen Trokel, Columbia University
- Investigators
- Stephen Trokel, MD, Principal investigator, Columbia University Dept. of Ophthalmology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02068430
- Sponsor's protocol ID
- AAAD2184
- Status last verified
- Feb 2023
- First submitted
- 20 Nov 2012
- Last updated
- 9 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Effectiveness of the UV-X System for Corneal Collagen Cross-Linking in Eyes With Refractory Corneal Infection
- ClinicalTrials.gov ID
- NCT02068430
- Acronym / sponsor ID
- AAAD2184
- Conditions
- Corneal Ulcers
- Keywords
- Corneal Ulcers, cross-linking, UVA, Riboflavin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Stephen TrokelUniversity, hospital or other
- Study start
- Nov 2008 (actual)
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 21 Feb 2014 (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.
This study will evaluate the Safety and Effectiveness of the UV-X System for Corneal Collagen Cross-Linking in Eyes with Corneal Infection. The treatment of UV-X system is to use the eyedrops of the riboflavin, also known as vitamin B2, and ultraviolet A (UVA) light. The eye drops are placed in affected eye and then affected cornea is exposed to UVA.
UVA/riboflavin corneal collagen cross-linking was first used to treat patients in 1998 in Dresden, Germany. Data to date obtained mostly by physicians outside the United States has strongly suggested this treatment as an acceptable alternative, and many subjects have had a lasting effect (no progression) 3-5 years after their initial treatment.
Detailed description
This study is designed to evaluate the safety and effectiveness of using the UV-X™ system for treating corneal ulcers that have proven refractory to conventional antibiotic treatment.
The UV-X™ system is a combination product consisting of a UVA 365 nm wavelength light source (UV-X™ Illumination System) and riboflavin (Medio-Cross® Riboflavin 0.1%) ophthalmic solution. The therapeutic effect is mediated by the photochemical interaction of the ultraviolet (UV) light with the riboflavin that has been saturated into the infected corneal stromal tissues.
The photochemical interaction of UVA light with riboflavin has been used to sterilize pathogens in blood and blood products. Pathogens including viruses, bacteria, fungi, and protozoa have shown to be sterilized using this photochemical process. Presumably singlet oxygen is produced by the interaction of the UVA with the riboflavin. It is this singlet oxygen that interacts with the pathogen's Deoxyribonucleic acid (DNA) in a sufficiently disruptive manner to render the exposed field sterile.
The cross-linking improves mechanical properties in the anterior stroma and has been shown to stabilize corneal structure in patients with progressive keratoconus and ectasias following refractive surgery. The same technology has been applied to a handful of patients with corneal ulcers and a single small series with bullous keratopathy. In no case was the patient worsened by this treatment. In the majority of the cases, considerable clinical reversal of a deteriorating clinical course was obtained. There has been debate about the mechanism of action of this beneficial effect. It has been speculated that a proteolytic collagenase enzyme was destroyed by the photochemical process. As an alternate, it has been suggested that the corneal collagen is strengthened by the cross linking and becomes more resistant to the infectious process. Finally a direct sterilization effect of the UVA light, the riboflavin, or the combination has been postulated. Recent laboratory work has shown that staphylococci cultures on an agar plate will be killed when exposed to the combination of UVA and riboflavin as used in these experiments. Neither the UVA nor the riboflavin alone had any bactericidal effect.
The procedure that has been used and that the investigators propose to study to treats corneal infections and ulcerations is identical to the procedure used to strengthen the cornea. It is performed by saturating the cornea with riboflavin 0.1% riboflavin solution and then exposing the riboflavin soaked cornea to UVA light. After the corneal stroma saturation is achieved, the infected tissues are exposed to UVA light at 365 nm and an irradiance of 3 mW/cm2 for 30 minutes. Exposure of the cornea to this combination of UVA light (365 nm; 3 mW/cm2 irradiation; 30 minutes duration) after topical administration of riboflavin appears to have a broad sterilization effect based on the photochemical interaction of the UVA and the riboflavin.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Riboflavin 0.1% & UV-X™ Illumination System | Experimental | Drug: Riboflavin 0.1%, Other: UV-X™ Illumination SystemUV-X Cross linking: After topical anesthesia, 1 drop of Riboflavin 0.1% ophthalmic solution will be instilled topically in the eye every 2 minutes for 30 minutes. At the end of the 30 minute riboflavin pre-treatment period, the eye will be examined with blue light for the presence of a yellow flare in the anterior chamber. When the yellow flare in the anterior chamber is confirmed, the eye will be aligned under the UV-X™ light with the treatment plane at a working distance that is 50mm from the UV-X™ beam aperture. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Subjects who have one eye that meets the following criteria:
- Showing no response to the therapy by one or more of the following criteria:
Key exclusion criteria (5 listed)
- All subjects meeting any of the following criteria will be excluded from this study:
- A corneal ulcer that has perforated
- A corneal ulcer that has produced a descemetocele.
- Women who may be breast-feeding and pregnant women.
- Herpetic infection suggested by history or clinical evaluation.
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 0.1%Also: RiboflavinAfter topical anesthesia, 1 drop of Riboflavin 0.1% ophthalmic solution will be instilled topically in the eye every 2 minutes for 30 minutes. At the end of the 30 minute riboflavin pre-treatment period, the eye will be examined with blue light for the presence of a yellow flare in the anterior chamber. | Drug | Riboflavin 0.1% & UV-X™ Illumination System |
| UV-X™ Illumination SystemAlso: UVA lightWhen the yellow flare in the anterior chamber is confirmed, the eye will be aligned under the UV-X™ light with the treatment plane at a working distance that is 50mm from the UV-X™ beam aperture. The correct aperture setting will be selected for the size of the eye (7.5 , 9.5, or 11 mm), and the eye will be irradiated for 30 minutes, during which time instillation of riboflavin will continue (1 drop every 2 minutes). At the end of 30 minutes, the UV light source will automatically switch to the off position. The operator will keep track of irradiation time independently to confirm the actual treatment time. | Other | Riboflavin 0.1% & UV-X™ Illumination System |
Primary outcome
Number of patients with healed corneal ulcers
Time frame: 6 months
Stabilization of the corneal ulcer: The endpoint will be the healing of the ulcer with re-epithelialization of its surface and stromal clearing. The patients will be followed on a daily basis until the ulcer has shown definite signs of resolution requiring a longer interval between exams or alternative therapeutic measures become necessary.
Number of adverse events
Time frame: 6 months
The conditions to be treated are severe and have considerable functional loss. Vision loss, pain, corneal perforation, and blindness are often outcomes of severe progressive corneal ulcers. An abrupt worsening of the clinical appearance of the cornea or a worsening of symptoms will be considered as an adverse event.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2023.
Related trials for Corneal Ulcers
Not yet recruiting
A Single-Center Clinical Study Evaluating the Efficacy and Safety of Allogeneic Natural Killer (NK) Cell Transplantation for Mooren's Ulcer
Cornea Disease
RecruitingPhase 2
Efficacy of Locally Delivered Allogeneic Mesenchymal Stromal Cells
Corneal Ulcer
RecruitingPhase 3
Parasitic Ulcer Treatment Trial
Acanthamoeba Keratitis
Recruiting
Intrastromal Moxifloxacin as an Adjunctive Therapy in Recalcitrant Bacterial Keratitis
Bacterial Keratitis, Recalcitrant Infectious Keratitis
Not yet recruitingPhase 2
Fluorometholone Study
Keratitis Bacterial, Corneal Ulcer (Diagnosis)
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.
Stephen Trokel, MD principal investigator
Columbia University Dept. of Ophthalmology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Riboflavin 0.1% and UV-X™ Illumination System in people with Corneal Ulcers, run by Stephen Trokel 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 12 inclusion and 5 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: finished, as of the sponsor's last update on 9 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Number of patients with healed corneal ulcers (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Feb 2023.