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Treatment of LSCD With DM

Primary Purpose

Limbal Stem-cell Deficiency, Congenital Aniridia

Status
Not yet recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
transplantation of a Descemet's Membrane corneal onlay, partial LSCD
transplantation of a Descemet's Membrane corneal onlay, total/near-total LSCD
Sponsored by
University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Limbal Stem-cell Deficiency focused on measuring congenital aniridia, limbal stem cell deficiency, Descemet's Membrane

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Arm 1: partial LSCD (involving less than 75% of the limbus, or <75% of the corneal surface) Visually significant (best-corrected visually acuity 20/100 or worse) Arm 2: total/near-total LSCD with recurrent erosions or PEDs (involving more than 75% of the limbus, or more than 75% of the corneal surface) Visually significant (best-corrected visually acuity 20/100 or worse) PLUS Persistent epithelial defects last >2 weeks despite maximal medical therapy OR Recurrent erosions occuring at least once every month Exclusion Criteria: Pregnant women Prisoners (vulnerable population) Adults lacking capacity to consent (vulnerable population) Adults unable to sign consent due to non-english speaking or illiterate (vulnerable population)

Sites / Locations

  • University of Minnesota

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Visually significant partial LSCD

Total/near-total LSCD with recurrent or persistent epithelial defects (PED)

Arm Description

Patient with visually significant partial LSCD, as defined by a best corrected visual acuity of 20/100 or less, and partial LSCD on slit lamp exam with at least 25% of the limbus intact or at least 25% of the corneal surface covered with corneal epithelium will be enrolled in the first arm.

Patient with visually significant total LSCD, as defined by a best corrected visual acuity of 20/100 or less, and total LSCD on slit lamp exam with over 25% of the limbus intact or less than 25% of the corneal surface covered with corneal epithelium; and a history of a persistent epithelial defect that has persisted over 2 weeks despite maximal medical therapy, or a history of recurrent epithelial erosions that occur more frequently than once a month; will be enrolled in the second arm.

Outcomes

Primary Outcome Measures

Visual improvement
Visual Acuity: Improvement in visual acuity over time will be measured as the difference in post-op visual acuity at post-operative week 1, month 1, month 3, and month 6 compared to pre-op visual acuity. Visual acuity will be assessed in study eyes with a standard Snellen Eye Chart.
Graft Retention on Slit Lamp Examination
Retention of the graft: Retention of the graft on the surface of the eye will be documented as present, absent, or indeterminant using slit lamp examination. For slit lamp examination, retention of the graft will be evidenced by visualization of a gentian violet orientation mark (s-stamp) that will be placed on all grafts at the time of tissue processing by the eye bank (prior to transplantation).
Graft Retention on Slit Lamp Photography.
Retention of the graft: In order to maintain photographic proof of the findings on slit lamp examination, slit lamp photography will also be taken. Study eyes will be photographed at the slit lamp at post-operative week 1, month 1, month 3, and month 6. Retention of the graft will be evidenced by visualization of a gentian violet orientation mark (s-stamp) that will be placed on all grafts at the time of tissue processing by the eye bank (prior to transplantation). This photographic documentation will assist in confirming the findings in outcome measure #2.
Incidence of Post-operative Adverse Events Requiring Treatment
Post-operative adverse events: Patients will be assessed at slit lamp at post-operative week 1, month 1, month 3, and month 6 for dislocation or opacification of the DM corneal onlay, PEDs, elevated intraocular pressure (IOP), and/or infectious keratitis to assess the safety of the therapy. Any persistent epithelial defect will be measured for size on slit lamp by recording the long and short diameter of any defect. IOP will be measured using a Goldman applanation. Infectious keratitis and membrane dislocation will be assessed at slit lamp during each post-operative visit.
Corneal Neovascularization on Slit Lamp Examination
Corneal Neovascularization: will be evaluated using slit lamp examination pre-operatively and post-operatively at week 1, month 1, month 3, and month 6. The degree of corneal neovascularization will be quantified using a previously established 10-point slit lamp examination score based on the extent of limbal involvement (number of quadrants involved - up to 4 points), the extent of corneal surface involvement (total area of corneal involved - up to 4 points), and whether the central visual axis is involved (up to 2 points).
Corneal Neovascularization on Slit Lamp Photography
In order to maintain photographic proof of the findings on slit lamp examination, slit lamp photography will also be taken. Photos will be taken pre-operatively and post-operatively at week 1, month 1, month 3, and month 6. The degree of corneal neovascularization on the photos will be compared to the documented 10-point slit lamp examination score from outcomes measure #6 to confirm the accuracy of the results. Again, the 10-point slit lamp examination score is based on the extent of limbal involvement (number of quadrants involved - up to 4 points), the extent of corneal surface involvement (total area of corneal involved - up to 4 points), and whether the central visual axis is involved (up to 2 points).
Corneal Epitheliopathy on Slit Lamp Examination
Corneal Epitheliopathy: will be evaluated using slit lamp examination pre-operatively and post-operatively at week 1, month 1, month 3, and month 6. The degree of corneal epitheliopathy will be quantified using a previously established 10-point slit lamp examination score based on the extent of limbal involvement (number of quadrants involved - up to 4 points), the extent of corneal surface involvement (total area of corneal involved - up to 4 points), and whether the central visual axis is involved (up to 2 points).
Corneal Epitheliopathy on Slit Lamp Photography
In order to maintain photographic proof of the findings on slit lamp examination, slit lamp photography will also be taken. Photos will be taken pre-operatively and post-operatively at week 1, month 1, month 3, and month 6. The degree of corneal epitheliopathy on the photos will be compared to the documented 10-point slit lamp examination score from outcomes measure #8 to confirm the accuracy of the results. Again, the 10-point slit lamp examination score is based on the extent of limbal involvement (number of quadrants involved - up to 4 points), the extent of corneal surface involvement (total area of corneal involved - up to 4 points), and whether the central visual axis is involved (up to 2 points).
Corneal epithelial thickness
Corneal epithelial thickness will be assessed as a metric of LSCD severity. Corneal epithelial thickness will be measured in cross-section on AS-OCT only.

Secondary Outcome Measures

Full Information

First Posted
March 29, 2023
Last Updated
September 18, 2023
Sponsor
University of Minnesota
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1. Study Identification

Unique Protocol Identification Number
NCT05909735
Brief Title
Treatment of LSCD With DM
Official Title
Treatment of Limbal Stem Cell Deficiency With Descemet's Membrane
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 1, 2023 (Anticipated)
Primary Completion Date
October 30, 2024 (Anticipated)
Study Completion Date
October 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Minnesota

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
Limbal Stem Cell Deficiency (LSCD) is a blinding disease that accounts for an estimated 15-20% of corneal blindness worldwide. Current treatments are limited. Traditional corneal transplantation with penetrating keratoplasty (PKP) is ineffective in treating these patients. Without a healthy population of limbal stem cells (LSC) to regenerate the corneal epithelium, standard corneal transplants will not re-epithelialize and will rapidly scar over or melt. The limbal niche is the microenvironment surrounding the LSCs that is critical for maintaining their survival and proliferative potential under physiologic conditions. Extracellular signals from the microenvironment are critical to the normal function and maintenance of pluripotent stem cells. Identifying an effective niche replacement is thus an important focus of limbal stem cell research and critical for advancing treatments for LSCD. Descemet's membrane (DM), an acellular, naturally occurring, basement membrane found on the posterior surface of the cornea, is a promising niche replacement. DM is routinely isolated and transplanted intraocularly with associated donor corneal endothelium for treatment of diseases like Fuchs' dystrophy and corneal bullous keratopathy that specifically affect DM and corneal endothelium. However, its application on the ocular surface has not been explored. DM is optically clear and highly resistant to collagenase digestion. This makes it very attractive as a long-term corneal on-lay and niche replacement on the surface of the eye. The anterior fetal banded layer of DM shares key compositional similarities with limbal basement membrane, which is a major component of the limbal niche. These similarities include limbus-specific extracellular matrix proteins such as collagen IV that is restricted to the α1, α2 subtypes, vitronectin, and BM40/SPARC. Of these, vitronectin and BM40/SPARC are known to promote proliferation of LSCs and induced pluripotent stem cells (iPSC) in culture. Because of this, DM is a promising biological membrane for establishing a niche-like substrate on the corneal surface in patients with LSCD. The purpose of this pilot study is to investigate the clinical efficacy of using DM as a corneal on-lay to promote corneal re-epithelialization in partial LSCD.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Limbal Stem-cell Deficiency, Congenital Aniridia
Keywords
congenital aniridia, limbal stem cell deficiency, Descemet's Membrane

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
This is an interventional non-comparative pilot clinical trial
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Visually significant partial LSCD
Arm Type
Experimental
Arm Description
Patient with visually significant partial LSCD, as defined by a best corrected visual acuity of 20/100 or less, and partial LSCD on slit lamp exam with at least 25% of the limbus intact or at least 25% of the corneal surface covered with corneal epithelium will be enrolled in the first arm.
Arm Title
Total/near-total LSCD with recurrent or persistent epithelial defects (PED)
Arm Type
Experimental
Arm Description
Patient with visually significant total LSCD, as defined by a best corrected visual acuity of 20/100 or less, and total LSCD on slit lamp exam with over 25% of the limbus intact or less than 25% of the corneal surface covered with corneal epithelium; and a history of a persistent epithelial defect that has persisted over 2 weeks despite maximal medical therapy, or a history of recurrent epithelial erosions that occur more frequently than once a month; will be enrolled in the second arm.
Intervention Type
Procedure
Intervention Name(s)
transplantation of a Descemet's Membrane corneal onlay, partial LSCD
Intervention Description
The worst seeing eye of these patients (or a randomized eye if vision is equal bilaterally) will be treated with superficial keratectomy to remove any pannus and debride the central corneal epithelium, followed by transplantation of a Descemet's membrane corneal onlay. Patient will be followed for 6 months and evaluated for improvement in visual acuity and improvement in limbal stem cell deficiency, and monitored for adverse events.
Intervention Type
Procedure
Intervention Name(s)
transplantation of a Descemet's Membrane corneal onlay, total/near-total LSCD
Intervention Description
The worst seeing eye of these patients (or a randomized eye if vision is equal bilaterally) will be treated with superficial keratectomy to remove any pannus and debride the central corneal epithelium, followed by transplantation of a Descemet's membrane (DM) corneal onlay. Patient will be followed for 6 months and evaluated for improvement in visual acuity, limbal stem cell deficiency, and persistent epithelial defects/recurrent erosions, and monitored for adverse events.
Primary Outcome Measure Information:
Title
Visual improvement
Description
Visual Acuity: Improvement in visual acuity over time will be measured as the difference in post-op visual acuity at post-operative week 1, month 1, month 3, and month 6 compared to pre-op visual acuity. Visual acuity will be assessed in study eyes with a standard Snellen Eye Chart.
Time Frame
180 days following intervention
Title
Graft Retention on Slit Lamp Examination
Description
Retention of the graft: Retention of the graft on the surface of the eye will be documented as present, absent, or indeterminant using slit lamp examination. For slit lamp examination, retention of the graft will be evidenced by visualization of a gentian violet orientation mark (s-stamp) that will be placed on all grafts at the time of tissue processing by the eye bank (prior to transplantation).
Time Frame
180 days following intervention
Title
Graft Retention on Slit Lamp Photography.
Description
Retention of the graft: In order to maintain photographic proof of the findings on slit lamp examination, slit lamp photography will also be taken. Study eyes will be photographed at the slit lamp at post-operative week 1, month 1, month 3, and month 6. Retention of the graft will be evidenced by visualization of a gentian violet orientation mark (s-stamp) that will be placed on all grafts at the time of tissue processing by the eye bank (prior to transplantation). This photographic documentation will assist in confirming the findings in outcome measure #2.
Time Frame
180 days following intervention
Title
Incidence of Post-operative Adverse Events Requiring Treatment
Description
Post-operative adverse events: Patients will be assessed at slit lamp at post-operative week 1, month 1, month 3, and month 6 for dislocation or opacification of the DM corneal onlay, PEDs, elevated intraocular pressure (IOP), and/or infectious keratitis to assess the safety of the therapy. Any persistent epithelial defect will be measured for size on slit lamp by recording the long and short diameter of any defect. IOP will be measured using a Goldman applanation. Infectious keratitis and membrane dislocation will be assessed at slit lamp during each post-operative visit.
Time Frame
180 days following intervention
Title
Corneal Neovascularization on Slit Lamp Examination
Description
Corneal Neovascularization: will be evaluated using slit lamp examination pre-operatively and post-operatively at week 1, month 1, month 3, and month 6. The degree of corneal neovascularization will be quantified using a previously established 10-point slit lamp examination score based on the extent of limbal involvement (number of quadrants involved - up to 4 points), the extent of corneal surface involvement (total area of corneal involved - up to 4 points), and whether the central visual axis is involved (up to 2 points).
Time Frame
180 days following intervention
Title
Corneal Neovascularization on Slit Lamp Photography
Description
In order to maintain photographic proof of the findings on slit lamp examination, slit lamp photography will also be taken. Photos will be taken pre-operatively and post-operatively at week 1, month 1, month 3, and month 6. The degree of corneal neovascularization on the photos will be compared to the documented 10-point slit lamp examination score from outcomes measure #6 to confirm the accuracy of the results. Again, the 10-point slit lamp examination score is based on the extent of limbal involvement (number of quadrants involved - up to 4 points), the extent of corneal surface involvement (total area of corneal involved - up to 4 points), and whether the central visual axis is involved (up to 2 points).
Time Frame
180 days following intervention
Title
Corneal Epitheliopathy on Slit Lamp Examination
Description
Corneal Epitheliopathy: will be evaluated using slit lamp examination pre-operatively and post-operatively at week 1, month 1, month 3, and month 6. The degree of corneal epitheliopathy will be quantified using a previously established 10-point slit lamp examination score based on the extent of limbal involvement (number of quadrants involved - up to 4 points), the extent of corneal surface involvement (total area of corneal involved - up to 4 points), and whether the central visual axis is involved (up to 2 points).
Time Frame
180 days following intervention
Title
Corneal Epitheliopathy on Slit Lamp Photography
Description
In order to maintain photographic proof of the findings on slit lamp examination, slit lamp photography will also be taken. Photos will be taken pre-operatively and post-operatively at week 1, month 1, month 3, and month 6. The degree of corneal epitheliopathy on the photos will be compared to the documented 10-point slit lamp examination score from outcomes measure #8 to confirm the accuracy of the results. Again, the 10-point slit lamp examination score is based on the extent of limbal involvement (number of quadrants involved - up to 4 points), the extent of corneal surface involvement (total area of corneal involved - up to 4 points), and whether the central visual axis is involved (up to 2 points).
Time Frame
180 days following intervention
Title
Corneal epithelial thickness
Description
Corneal epithelial thickness will be assessed as a metric of LSCD severity. Corneal epithelial thickness will be measured in cross-section on AS-OCT only.
Time Frame
180 days following intervention

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Arm 1: partial LSCD (involving less than 75% of the limbus, or <75% of the corneal surface) Visually significant (best-corrected visually acuity 20/100 or worse) Arm 2: total/near-total LSCD with recurrent erosions or PEDs (involving more than 75% of the limbus, or more than 75% of the corneal surface) Visually significant (best-corrected visually acuity 20/100 or worse) PLUS Persistent epithelial defects last >2 weeks despite maximal medical therapy OR Recurrent erosions occuring at least once every month Exclusion Criteria: Pregnant women Prisoners (vulnerable population) Adults lacking capacity to consent (vulnerable population) Adults unable to sign consent due to non-english speaking or illiterate (vulnerable population)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Meaghyn Kramer, BA
Phone
612-625-4108
Email
krame706@umn.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephen Kaufman, MD
Organizational Affiliation
University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Teresa Dalager
Phone
612-625-4108
Email
dalag020@umn.edu

12. IPD Sharing Statement

Learn more about this trial

Treatment of LSCD With DM

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