Progressive KeratoconusT-iontoCLNCT02117999
Transepithelial Corneal Cross-linking Using Iontophoresis
A study testing Cross-linking with iontophoresis and Standard corneal cross-linking in people with Progressive Keratoconus, run by Fondazione G.B. Bietti, IRCCS at 1 site in Italy.
Trial summary
The purpose of the present Randomized Clinical Trial (RCT) is to compare the efficacy and safety of transepithelial corneal cross-linking using iontophoresis (T-ionto CL) to treat progressive keratoconus in comparison with standard cross-linking (standard CL). Read more about this study
- Who is it for?
- Ages 18 to 46 years
- Conditions the study is for
- Progressive Keratoconus
- What is being tested?
- Cross-linking with iontophoresis and Standard corneal cross-linking
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteItaly
- Study dates
- Jan 2014to Sep 2016
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 46 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Diagnosis of progressive keratoconus
Who cannot join
- Anterior corneal curvature steeper than 61 D;
- central corneal thickness <400 um
- corneal scarring;
- descemetocele;
- history of herpetic keratitis;
- Concomitant eye diseases;
Show all 10Show fewer
- Inflammatory eye diseases;
- Glaucoma;
- Cataract;
- Pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized Clinical Trial Comparing Transepithelial Corneal Cross-linking Using Iontophoresis and Standard Corneal Cross-linking for the Treatment of Keratoconus
The purpose of the present Randomized Clinical Trial (RCT) is to compare the efficacy and safety of transepithelial corneal cross-linking using iontophoresis (T-ionto CL) to treat progressive keratoconus in comparison with standard cross-linking (standard CL).
Read the detailed description
Keratoconus is a progressive corneal ectatic disease causing visual impairment by inducing irregular astigmatism and corneal opacity. This disorder typically begins during the second decade of life and, in severe forms, may need a corneal transplantation. Corneal cross-linking with riboflavin and UV-A is a procedure intended to halt keratoconus progression. It generates additional chemical bonds between stromal proteins in order to stiffen the corneal tissue. Standard CL includes epithelial removal and stroma soaking with dextran-enriched 0.1% riboflavin solution for 30 minutes before being exposed to ultraviolet-A radiation using a 3mW/cm2 lamp for 30 minutes.
Epithelial debridement exposes the cornea to a risk of side effects, such as pain for the first two post-operative days, temporary loss of visual acuity during the first three months, and serious complications, such as infection and stromal opacity due to corneal scarring.
Iontophoresis is a non invasive technique in which a weak electric current is used to enhance the penetration of hypotonic 0.1% riboflavin-5-phosphate solution into the corneal stroma through the intact epithelium. After iontophoresis, the corneal tissue is irradiated using a 10 mW/cm2 for 9 minutes (T-ionto CL). From previous experimental work (Lombardo M. et al. JCRS 2014 and JCRS 2015), the investigators provided evidence that T-ionto CL increases the stiffness of human corneas with results almost comparable with standard CL. The new procedure holds the promise to be as effective as the standard procedure while minimizing all the related risks. It is object of the present clinical trial to randomize patients with progressive keratoconus to T-ionto CL and standard CL and compare efficacy and safety of treatments.
- Conditions
- Progressive Keratoconus
- Being tested
- Cross-linking with iontophoresis, Standard corneal cross-linking
- Keywords
- corneal cross-linking, transepithelial corneal cross-linking, iontophoresis, progressive keratoconus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cross-linking with iontophoresisDevice
Also called Ricrolin+
The procedure involves a constant current source and two electrodes. The active electrode is a bath tube, which includes a stainless steel grid, placed into the cup at a minimal distance from the cornea. The reservoir is filled with dextran-free, hypotonic riboflavin-5-phosphate solution. The generator applies a constant current of 1mA for a preset period of 5 min. After the riboflavin administration by iontophoresis, the cornea is irradiated using a UVA lamp of 10mW/cm2 for 9 minutes.
Standard corneal cross-linkingDevice
Also called Ricrolin
In the standard CL, the epithelium is mechanically removed. Then, a solution of riboflavin is instilled each minute for 30 minutes. Corneas are irradiated using a UVA lamp of 3mW/cm2 for 30 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Cross-linking with iontophoresis | Experimental | Transepithelial cross-linking by using iontophoresis to administer riboflavin into the corneal stroma Receives: Device: Cross-linking with iontophoresis |
| Standard corneal cross-linking | Active comparator | Standard corneal cross-linking includes de-epithelialization and stromal soaking by applying drops of riboflavin Receives: Device: Standard corneal cross-linking |
What is being measured
The primary outcome is the main question the study is designed to answer.
K-max
Measuring maximum keratometry (K-max), measured in diopters (D), derived from computerized videokeratography.
Measured: Changes from baseline in Kmax at 12 months
Corneal Endothelial Cell Density
Endothelial cell density (ECD) will be evaluated using specular microscopy
Measured: Changes from baseline in ECD at 12 months
Secondary outcomes (4)
Optical Aberrations
Optical aberrations of the eye will be measured using dynamic skyascopy. Corneal wavefront aberration will be measured using Placido disk topographer and Scheimpflug tomographer.
Measured: Changes from baseline at 12 months.
Visual Acuity
Visual acuity tested using ETDRS
Measured: Changes from baseline at 12 months.
Contrast Sensitivity
Contrast sensitivity tested using Pelli-Robson chart
Measured: Changes from baseline at 12 months.
Central Retinal Thickness
Central retinal thickness (1 mm ETDRS map) will be measured before and after CXL procedures
Measured: Changes from baseline at 12 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2014 (estimated)
- Study startJan 2014
- Primary completionJun 2016
- Study completionSep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Progressive 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Consecutive patients were randomized, using block randomization model, in one of the arm
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondazione G.B. Bietti, IRCCS
- Sponsor type
- University, hospital or other
- Collaborators
- CNR Institute for chemical and physical processes (IPCF), Messina
- Responsible party
- Principal investigator, Marco Lombardo, Fondazione G.B. Bietti, IRCCS
- Investigators
- Marco Lombardo, MD, PhD, Principal investigator, Fondazione G.B. Bietti, IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02117999
- Sponsor's protocol ID
- SEA27
- Other IDs
- PON01_00110
- Acronym
- T-iontoCL
- Status last verified
- Aug 2019
- First submitted
- 11 Apr 2014
- Last updated
- 8 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No: still investigating this study population up to 3 years after treatment
Publications
Spoerl E, Huhle M, Seiler T. Induction of cross-links in corneal tissue. Exp Eye Res. 1998 Jan;66(1):97-103. doi: 10.1006/exer.1997.0410.
PubMed 9533835Hao J, Li SK, Liu CY, Kao WW. Electrically assisted delivery of macromolecules into the corneal epithelium. Exp Eye Res. 2009 Dec;89(6):934-41. doi: 10.1016/j.exer.2009.08.001. Epub 2009 Aug 12.
PubMed 19682448Eljarrat-Binstock E, Domb AJ. Iontophoresis: a non-invasive ocular drug delivery. J Control Release. 2006 Feb 21;110(3):479-89. doi: 10.1016/j.jconrel.2005.09.049. Epub 2005 Dec 15.
PubMed 16343678Bikbova G, Bikbov M. Transepithelial corneal collagen cross-linking by iontophoresis of riboflavin. Acta Ophthalmol. 2014 Feb;92(1):e30-4. doi: 10.1111/aos.12235. Epub 2013 Jul 15.
PubMed 23848196Meek KM, Hayes S. Corneal cross-linking--a review. Ophthalmic Physiol Opt. 2013 Mar;33(2):78-93. doi: 10.1111/opo.12032.
PubMed 23406488Lombardo M, Serrao S, Lombardo G, Schiano-Lomoriello D. Two-year outcomes of a randomized controlled trial of transepithelial corneal crosslinking with iontophoresis for keratoconus. J Cataract Refract Surg. 2019 Jul;45(7):992-1000. doi: 10.1016/j.jcrs.2019.01.026. Epub 2019 Apr 16.
PubMed 31003798Lombardo M, Giannini D, Lombardo G, Serrao S. Randomized Controlled Trial Comparing Transepithelial Corneal Cross-linking Using Iontophoresis with the Dresden Protocol in Progressive Keratoconus. Ophthalmology. 2017 Jun;124(6):804-812. doi: 10.1016/j.ophtha.2017.01.040. Epub 2017 Mar 7.
PubMed 28283279
Study at a glance
From the registry record, last updated by the sponsor on 8 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Clinical Trial Comparing Transepithelial Corneal Cross-linking Using Iontophoresis and Standard Corneal Cross-linking for the Treatment of Keratoconus
- ClinicalTrials.gov ID
- NCT02117999
- Acronym / sponsor ID
- T-iontoCL / SEA27
- Conditions
- Progressive Keratoconus
- Keywords
- corneal cross-linking, transepithelial corneal cross-linking, iontophoresis, progressive keratoconus
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Fondazione G.B. Bietti, IRCCSUniversity, hospital or other
- Collaborators
- CNR Institute for chemical and physical processes (IPCF), Messina
- Study start
- Jan 2014 (actual)
- Primary completion
- Jun 2016 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 21 Apr 2014 (estimated)
- Results
- Posted 8 Aug 2019
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 the present Randomized Clinical Trial (RCT) is to compare the efficacy and safety of transepithelial corneal cross-linking using iontophoresis (T-ionto CL) to treat progressive keratoconus in comparison with standard cross-linking (standard CL).
Detailed description
Keratoconus is a progressive corneal ectatic disease causing visual impairment by inducing irregular astigmatism and corneal opacity. This disorder typically begins during the second decade of life and, in severe forms, may need a corneal transplantation. Corneal cross-linking with riboflavin and UV-A is a procedure intended to halt keratoconus progression. It generates additional chemical bonds between stromal proteins in order to stiffen the corneal tissue. Standard CL includes epithelial removal and stroma soaking with dextran-enriched 0.1% riboflavin solution for 30 minutes before being exposed to ultraviolet-A radiation using a 3mW/cm2 lamp for 30 minutes.
Epithelial debridement exposes the cornea to a risk of side effects, such as pain for the first two post-operative days, temporary loss of visual acuity during the first three months, and serious complications, such as infection and stromal opacity due to corneal scarring.
Iontophoresis is a non invasive technique in which a weak electric current is used to enhance the penetration of hypotonic 0.1% riboflavin-5-phosphate solution into the corneal stroma through the intact epithelium. After iontophoresis, the corneal tissue is irradiated using a 10 mW/cm2 for 9 minutes (T-ionto CL). From previous experimental work (Lombardo M. et al. JCRS 2014 and JCRS 2015), the investigators provided evidence that T-ionto CL increases the stiffness of human corneas with results almost comparable with standard CL. The new procedure holds the promise to be as effective as the standard procedure while minimizing all the related risks. It is object of the present clinical trial to randomize patients with progressive keratoconus to T-ionto CL and standard CL and compare efficacy and safety of treatments.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Consecutive patients were randomized, using block randomization model, in one of the arm
| Arm | Type | Receives |
|---|---|---|
| Cross-linking with iontophoresis | Experimental | Device: Cross-linking with iontophoresisTransepithelial cross-linking by using iontophoresis to administer riboflavin into the corneal stroma |
| Standard corneal cross-linking | Active comparator | Device: Standard corneal cross-linkingStandard corneal cross-linking includes de-epithelialization and stromal soaking by applying drops of riboflavin |
Who may qualify
- Ages
- 18 to 46 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Diagnosis of progressive keratoconus
Key exclusion criteria (10 listed)
- Anterior corneal curvature steeper than 61 D;
- central corneal thickness <400 um
- corneal scarring;
- descemetocele;
- history of herpetic 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 |
|---|---|---|
| Cross-linking with iontophoresisAlso: Ricrolin+The procedure involves a constant current source and two electrodes. The active electrode is a bath tube, which includes a stainless steel grid, placed into the cup at a minimal distance from the cornea. The reservoir is filled with dextran-free, hypotonic riboflavin-5-phosphate solution. The generator applies a constant current of 1mA for a preset period of 5 min. After the riboflavin administration by iontophoresis, the cornea is irradiated using a UVA lamp of 10mW/cm2 for 9 minutes. | Device | Cross-linking with iontophoresis |
| Standard corneal cross-linkingAlso: RicrolinIn the standard CL, the epithelium is mechanically removed. Then, a solution of riboflavin is instilled each minute for 30 minutes. Corneas are irradiated using a UVA lamp of 3mW/cm2 for 30 minutes. | Device | Standard corneal cross-linking |
Primary outcome
K-max
Time frame: Changes from baseline in Kmax at 12 months
Measuring maximum keratometry (K-max), measured in diopters (D), derived from computerized videokeratography.
Corneal Endothelial Cell Density
Time frame: Changes from baseline in ECD at 12 months
Endothelial cell density (ECD) will be evaluated using specular microscopy
4 secondary outcomes
Optical Aberrations
Time frame: Changes from baseline at 12 months.
Visual Acuity
Time frame: Changes from baseline at 12 months.
Contrast Sensitivity
Time frame: Changes from baseline at 12 months.
Central Retinal Thickness
Time frame: Changes from baseline at 12 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 9533835Spoerl E, Huhle M, Seiler T. Induction of cross-links in corneal tissue. Exp Eye Res. 1998 Jan;66(1):97-103. doi: 10.1006/exer.1997.0410.
- Background: PubMed 19682448Hao J, Li SK, Liu CY, Kao WW. Electrically assisted delivery of macromolecules into the corneal epithelium. Exp Eye Res. 2009 Dec;89(6):934-41. doi: 10.1016/j.exer.2009.08.001. Epub 2009 Aug 12.
- Background: PubMed 16343678Eljarrat-Binstock E, Domb AJ. Iontophoresis: a non-invasive ocular drug delivery. J Control Release. 2006 Feb 21;110(3):479-89. doi: 10.1016/j.jconrel.2005.09.049. Epub 2005 Dec 15.
- Background: PubMed 23848196Bikbova G, Bikbov M. Transepithelial corneal collagen cross-linking by iontophoresis of riboflavin. Acta Ophthalmol. 2014 Feb;92(1):e30-4. doi: 10.1111/aos.12235. Epub 2013 Jul 15.
- Background: PubMed 23406488Meek KM, Hayes S. Corneal cross-linking--a review. Ophthalmic Physiol Opt. 2013 Mar;33(2):78-93. doi: 10.1111/opo.12032.
- Derived from this study: PubMed 31003798Lombardo M, Serrao S, Lombardo G, Schiano-Lomoriello D. Two-year outcomes of a randomized controlled trial of transepithelial corneal crosslinking with iontophoresis for keratoconus. J Cataract Refract Surg. 2019 Jul;45(7):992-1000. doi: 10.1016/j.jcrs.2019.01.026. Epub 2019 Apr 16.
- Derived from this study: PubMed 28283279Lombardo M, Giannini D, Lombardo G, Serrao S. Randomized Controlled Trial Comparing Transepithelial Corneal Cross-linking Using Iontophoresis with the Dresden Protocol in Progressive Keratoconus. Ophthalmology. 2017 Jun;124(6):804-812. doi: 10.1016/j.ophtha.2017.01.040. Epub 2017 Mar 7.
- Inclusion and exclusion criteria to the present RCT are shown in the main website pageLink provided by the sponsor.
- Individual participant dataSharing planned: No. still investigating this study population up to 3 years after treatment
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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.
Marco Lombardo, MD, PhD principal investigator
Fondazione G.B. Bietti, IRCCS
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cross-linking with iontophoresis and Standard corneal cross-linking in people with Progressive Keratoconus, run by Fondazione G.B. Bietti, IRCCS at 1 site in Italy.
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 1 inclusion and 10 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 8 Aug 2019. 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 Italy. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
K-max (time frame: Changes from baseline in Kmax at 12 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?
On the ClinicalTrials.gov record for NCT02117999, which also lists 7 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 Aug 2019; AzTrials last refreshed its copy on 31 Oct 2026.