Corneal Crosslinking Treatment Study
Primary Purpose
Progressive Keratoconus
Status
Recruiting
Phase
Phase 4
Locations
Sweden
Study Type
Interventional
Intervention
Corneal crosslinking: CXL (UVA 9mW/cm2)
Isotonic riboflavin
Hypotonic riboflavin
Iontophoresis
Sponsored by
About this trial
This is an interventional treatment trial for Progressive Keratoconus focused on measuring corneal crosslinking
Eligibility Criteria
Inclusion Criteria:
- Progress in keratoconic eye. We define progress as an increase in Kmax of 1.0 diopter in 1 year or 0.5 diopter in 6 months. This increase in Kmax will be accepted as progression if concomitant changes tomographic parameters.
Exclusion Criteria:
- Concurrent ocular infection or corneal disease other than keratoconus.
- Pregnancy.
- Treatment with Isotretinoin.
Sites / Locations
- Skåne University HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Active Comparator
Arm Label
Isotonic riboflavin
Hypotonic riboflavin
Iontophoresis
Arm Description
CXL (UVA 9mW/cm2) treatment using isotonic riboflavin
CXL (UVA 9mW/cm2) using hypotonic riboflavin
Iontophoresis with Ricrolin with following CXL (UVA 9mW/cm2).
Outcomes
Primary Outcome Measures
Postoperative change in visual acuity
Uncorrected visual acuity (UCVA) and best spectacle corrected visual acuity (BSCVA)
Postoperative change in Kmax
Maximum corneal steepness
Secondary Outcome Measures
Postoperative change in astigmatism
Corneal astigmatism
postoperative change in corneal nerve cell density
Corneal nerve cell density will be evaluated using confocal microscopy
Postoperative change in Keratocyte cell density
Keratocyte cell density will be evaluated using confocal microscopy
Postoperative change in endothelial cell count
Endothelial cell count will be evaluated using confocal microscopy
Postoperative change in demarcation lines
Identification of the demarcation lines with confocal microscopy will help establishing how deep was the effect of the CXL treatment.
Postoperative change in the corneal thickness during CXL treatment
Corneal pachymetry is the process of measuring the thickness of the cornea
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04427956
Brief Title
Corneal Crosslinking Treatment Study
Official Title
Prospective Randomised Corneal Crosslinking Study
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 23, 2017 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Region Skane
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Three different protocols for inducing corneal crosslinks in subjets with progressive keratoconus will be evaluated in this randomised clinical study.
Detailed Description
Riboflavin does not penetrate the intact corneal epithelium. Corneal cross linking (CXL) is typically performed using the so-called "Dresden protocol". The Dresden protocol states 30 minutes of UVA-radiation (3mW/cm2) but a 10 minute irradiation protocol (9mW/cm2) is frequently used. Both of the protocols involve mechanical removal of the epithelium over the central 8 mm of the corneal surface. The first days after treatment therefore involves some degree of pain, often intense, and the presence of a healing epithelial defect may be associated with development of infiltrates in the cornea. A number of approaches have been evaluated in order to promote riboflavin penetration through the intact epithelium, of which iontophoresis appears most promising. Keratoconic corneas are thin at the cone location and sometimes it is difficult to maintain the safety margin of 400 microns during corneal crosslinking. Instead of using isotonic standard riboflavin, a swelling effect of the cornea can be obtained by using hypotonic riboflavin. However, the latter has been indicated as less effective in the process of inducing cross links.
Eighty-one of 81 patients of various degrees of keratoconus will be randomised to one of the following groups: 1) CXL (UVA 9mW/cm2) using isotonic riboflavin, or 2) CXL (UVA 9mW/cm2) using hypotonic riboflavin or 3) Iontophoresis with Ricrolin with following CXL (UVA 9mW/cm2).
Hypothesis:
i) CXL with hypotonic riboflavin or CXL with Ricrolin administered by iontophoresis or CXL with isotonic riboflavin is non-inferior compared to standard CXL with isotonic riboflavin.
ii) The morphological structure post-CXL in the three different groups will be similar without any significant differences.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Progressive Keratoconus
Keywords
corneal crosslinking
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Prospective randomized interventional clinical trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
81 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Isotonic riboflavin
Arm Type
Active Comparator
Arm Description
CXL (UVA 9mW/cm2) treatment using isotonic riboflavin
Arm Title
Hypotonic riboflavin
Arm Type
Active Comparator
Arm Description
CXL (UVA 9mW/cm2) using hypotonic riboflavin
Arm Title
Iontophoresis
Arm Type
Active Comparator
Arm Description
Iontophoresis with Ricrolin with following CXL (UVA 9mW/cm2).
Intervention Type
Procedure
Intervention Name(s)
Corneal crosslinking: CXL (UVA 9mW/cm2)
Intervention Description
CXL treatment with UVA-radiation (9mW/cm2) with a 10 minute irradiation protocol.
Intervention Type
Drug
Intervention Name(s)
Isotonic riboflavin
Intervention Description
CXL protocol with isotonic riboflavin
Intervention Type
Drug
Intervention Name(s)
Hypotonic riboflavin
Intervention Description
CXL protocol with hypotonic riboflavin
Intervention Type
Procedure
Intervention Name(s)
Iontophoresis
Intervention Description
CXL protocol with iontophoresis and ricrolin
Primary Outcome Measure Information:
Title
Postoperative change in visual acuity
Description
Uncorrected visual acuity (UCVA) and best spectacle corrected visual acuity (BSCVA)
Time Frame
Patients will be evaluated 1, 6, 12 and 24 months after treatment.
Title
Postoperative change in Kmax
Description
Maximum corneal steepness
Time Frame
Patients will be evaluated 1, 6, 12 and 24 months after treatment.
Secondary Outcome Measure Information:
Title
Postoperative change in astigmatism
Description
Corneal astigmatism
Time Frame
Patients will be evaluated 1, 6, 12 and 24 months after treatment.
Title
postoperative change in corneal nerve cell density
Description
Corneal nerve cell density will be evaluated using confocal microscopy
Time Frame
Confocal microscopy will be performed at 6 and 12 months.
Title
Postoperative change in Keratocyte cell density
Description
Keratocyte cell density will be evaluated using confocal microscopy
Time Frame
Confocal microscopy will be performed at 6 and 12 months.
Title
Postoperative change in endothelial cell count
Description
Endothelial cell count will be evaluated using confocal microscopy
Time Frame
Confocal microscopy will be performed at 6 and 12 months.
Title
Postoperative change in demarcation lines
Description
Identification of the demarcation lines with confocal microscopy will help establishing how deep was the effect of the CXL treatment.
Time Frame
Confocal microscopy will be performed at 6 and 12 months.
Title
Postoperative change in the corneal thickness during CXL treatment
Description
Corneal pachymetry is the process of measuring the thickness of the cornea
Time Frame
Corneal pachymetry will be evaluated before and then every 5 minutes during 30 minutes under CXL treatment.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Progress in keratoconic eye. We define progress as an increase in Kmax of 1.0 diopter in 1 year or 0.5 diopter in 6 months. This increase in Kmax will be accepted as progression if concomitant changes tomographic parameters.
Exclusion Criteria:
Concurrent ocular infection or corneal disease other than keratoconus.
Pregnancy.
Treatment with Isotretinoin.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ingemar Gustafsson, M.D Ph.D
Phone
004640332548
Email
ingemar.gustafsson@med.lu.se
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ingemar Gustafsson, MD
Organizational Affiliation
Region Skåne
Official's Role
Principal Investigator
Facility Information:
Facility Name
Skåne University Hospital
City
Lund
State/Province
Skåne
ZIP/Postal Code
22242
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ingemar Gustafsson, MD, PhD
Phone
004640332548
Email
ingemar.gustafsson@med.lu.se
12. IPD Sharing Statement
Plan to Share IPD
No
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Corneal Crosslinking Treatment Study
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