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Impact of Donor Diabetes on DMEK Success and Endothelial Cell Loss (DEKS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05134480
Recruitment Status : Recruiting
First Posted : November 26, 2021
Last Update Posted : February 15, 2022
Sponsor:
Collaborators:
Jaeb Center for Health Research
National Eye Institute (NEI)
Information provided by (Responsible Party):
Jonathan Lass, MD, Case Western Reserve University

Brief Summary:
This double-masked multi-center trial will evaluate the association of diabetes in the cornea donor with transplant success and loss of endothelial cells one year following Descemet membrane endothelial keratoplasty (DMEK). Study eyes will be assigned to receive either a cornea from a donor without diabetes or a cornea from a donor with diabetes.

Condition or disease Intervention/treatment Phase
Corneal Endothelial Decompensation Fuchs' Endothelial Dystrophy Procedure: Descemet membrane endothelial keratoplasty Not Applicable

Detailed Description:

This study will address concerns about the suitability of corneas from donors with diabetes for use with DMEK through a prospective, masked, multi-center clinical trial in which the donor corneas are assigned by diabetes status in the same distribution proportion (2:1 distribution of tissue from donors without diabetes to tissue from donors with diabetes) currently used in the USA. The DEKS will assess graft success and endothelial cell density through 1 year following DMEK to determine whether the surgical success rate with corneas from donors with well characterized diabetes (including post-mortem hemoglobin A1c (HbA1c) and advanced glycation endproducts (AGE) testing) is inferior to the rate with donors without diabetes. The investigators hypothesize that the majority of donor corneas from individuals with diabetes will be suitable, but that a portion of donors with a higher diabetes severity scale, and/or poorer control based on HbA1c will have a greater risk for graft failure and endothelial cell loss. This study will also examine collected skin biopsies to determine whether high levels of AGE biomarkers in donor skin tissue - which quantifies disease severity over many years (and possibly coupled with elevated HbA1c levels) - is associated with greater risk for graft failure and cell loss. This novel approach to characterization of donor tissue can provide a paradigm shift in the risk assessment of transplanted corneas from diabetic donors. The effect of recipient diabetes on keratoplasty success and cell loss will also be studied in a rigorous manner to determine the potential combined effect of donor and recipient diabetes status.

In summary, this study is designed to determine if non-diabetic donor corneas are superior to diabetic donor corneas in terms of both graft success and endothelial cell density outcomes, with an additional specific aim to determine whether donors with a higher diabetes severity scale, and/or poorer control based on HbA1c are driving the effect. This study will also determine whether a high AGE/A1c metric is also associated with the potential superiority finding and establish a novel composite score (severity score, HbA1c and AGE/A1c) based on these metrics that can be used to identify high versus low risk diabetic donors. This distinction may enable eye banks to potentially utilize the majority of donors with diabetes for EK surgery, while excluding the severely affected donors with diabetes.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1420 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Prospective, randomized, double-masked (participant and clinical site) clinical trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: The participants and the clinical site staff, including the investigators and outcomes assessor will be masked to all donor tissue parameters except storage solution.
Primary Purpose: Treatment
Official Title: Diabetes Endothelial Keratoplasty Study (DEKS): Impact of Diabetes on Corneal Transplant Success and Endothelial Cell Loss
Actual Study Start Date : January 21, 2022
Estimated Primary Completion Date : March 30, 2025
Estimated Study Completion Date : March 30, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Cornea from donor with diabetes
Participant will be assigned a cornea recovered from a donor with diabetes.
Procedure: Descemet membrane endothelial keratoplasty
cornea transplant procedure to replace dysfunctional endothelial cell layer

Active Comparator: Cornea from donor without diabetes
Participant will be assigned a cornea recovered from a donor without diabetes.
Procedure: Descemet membrane endothelial keratoplasty
cornea transplant procedure to replace dysfunctional endothelial cell layer




Primary Outcome Measures :
  1. Graft failure [ Time Frame: 1 year ]
    Graft failure is defined as the occurrence of one of the following: a graft which requires replacement for any reason or the recipient cornea remains cloudy after surgery without clearing for 8 weeks or longer


Secondary Outcome Measures :
  1. Endothelial cell density [ Time Frame: 1 year ]
    Central corneal endothelial cell density assessed with specular microscopy



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   30 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Participant Inclusion Criteria:

  1. Age range 30- < 91 years with minimum life expectancy of at least 1 year
  2. Willingness to return to study site for follow up at 1 month and 1 year
  3. Fluent in English or Spanish
  4. Willingness to have fingerstick blood sample collected to determine HbA1c level at entry and at 1 year. The participant must agree to have their primary care provider contacted (or an appropriate referral provided) if they were not known to have diabetes and the HbA1c suggests they may have diabetes. Similarly, if already known to have diabetes and the HbA1c is high, the participant must agree to have their primary care provider contacted or an appropriate referral provided.
  5. Has at least one eye clinically recommended for DMEK that is able to be scheduled for DMEK between 5 to 90 days after enrollment. If second eye is enrolled, it must be scheduled for DMEK between 7 days and 6 months after DMEK on the first eye.
  6. Has a condition related to endothelial dysfunction which will be treated by DMEK. Eligible indications for DMEK include:

    1. Presence of Fuchs endothelial corneal dystrophy (FECD) meeting at least one of the following: phakic FECD with or without cataract (triple procedure including DMEK for FECD, cataract extraction and posterior chamber intraocular lens implantation (IOL) is allowed)
    2. pseudophakic FECD with posterior capsule supported, sulcus supported, or scleral-fixated posterior chamber IOL
    3. pseudophakic corneal edema with posterior capsule supported, sulcus supported, or scleral-fixated posterior chamber IOL without FECD
    4. failed Descemet stripping automated endothelial keratoplasty (DSAEK) or DMEK originally performed for the same indications above without current exclusionary criteria, as described below

Exclusion Criteria:

  1. Pregnant or planning to become pregnant prior to the DMEK study surgery, based on verbal report.
  2. Lack cognitive capacity such that consent could not be provided.
  3. Presence of a condition that has a high probability for failure (e.g., failed penetrating keratoplasty, uncontrolled uveitis)
  4. Stromal vascularization that will impede assessment of recipient stroma clarity
  5. Other primary endothelial dysfunction conditions including posterior polymorphous corneal dystrophy and congenital hereditary corneal dystrophy.
  6. Indication for surgery that is not suitable for DMEK (e.g, keratoconus, stromal dystrophies and scars)
  7. Aphakic corneal edema with or without FECD
  8. Anterior chamber IOL in study eye prior to DMEK or planned placement of anterior chamber IOL during DMEK
  9. Presence of vitreous in the anterior chamber
  10. Planned IOL exchange of an anterior chamber IOL with a posterior chamber IOL in study eye at time of study DMEK
  11. Pre-operative central sub-epithelial or stromal scarring that could impact post-operative recipient stromal clarity assessment
  12. Presence of anterior synechiae
  13. Peripheral anterior synechiae in the angle greater than a total of three clock hours
  14. Uncontrolled glaucoma with or without prior filtering surgery, tube shunt placement, or MIGS. Uncontrolled glaucoma is defined as intraocular pressure > 25mm Hg.
  15. Controlled glaucoma with prior tube shunt placement for glaucoma (controlled glaucoma with minimally invasive glaucoma surgery (MIGS) or trabeculectomy is allowed)
  16. Fellow eye visual acuity < 20/200 due to an ocular condition other than a cornea disease that would be a candidate for DMEK
  17. Intraocular pressure <8 mmHg
  18. Topical Rho kinase inhibitor, including netarsudil, used within 1 month prior to study entry and anticipated during the course of the study
  19. Fellow eye enrolled in the DEKS that has met study-criteria for graft failure.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05134480


Contacts
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Contact: Loretta Szczotka-Flynn, OD, PhD 216-844-7984 Loretta.Szczotka-Flynn@uhhospitals.org

Locations
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United States, Indiana
Price Vision Group Recruiting
Indianapolis, Indiana, United States, 46260
Contact: Marianne Price, PhD    317-814-2990    mprice@cornea.org   
United States, Michigan
Verdier Eye Center Recruiting
Grand Rapids, Michigan, United States, 49546
Contact: Paula Johnson, COA    616-949-2001 ext 1112    pjohnson@vecgr.com   
Sponsors and Collaborators
Case Western Reserve University
Jaeb Center for Health Research
National Eye Institute (NEI)
Investigators
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Study Chair: Jonathan Lass, MD Case Western Reserve University
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Responsible Party: Jonathan Lass, MD, Study Chair, Case Western Reserve University
ClinicalTrials.gov Identifier: NCT05134480    
Other Study ID Numbers: DEKS
1UG1EY030039-01A1 ( U.S. NIH Grant/Contract )
1UG1EY030030-01A1 ( U.S. NIH Grant/Contract )
First Posted: November 26, 2021    Key Record Dates
Last Update Posted: February 15, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data collected for this study will be analyzed and stored at the Jaeb Center for Health Research. After the study is completed, the de-identified, archived data will be made publicly available. Further, some data and images may be requested and shared with other researchers under a Data Use Agreement as a limited data set, since other than date of collection, there are no other identifiable elements. No additional identifying information shall be provided in a manner that would make the human subjects readily identifiable.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: Data will be made available indefinitely after publication of the study results, which is anticipated by April, 2026.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Fuchs' Endothelial Dystrophy
Corneal Dystrophies, Hereditary
Corneal Diseases
Eye Diseases
Eye Diseases, Hereditary
Genetic Diseases, Inborn