Limbus-derived Stem Cells for Prevention of Postoperative Corneal Haze

Pilot Clinical Trial to Assess the Safety of Limbus-derived Corneal Stem Cells in Prevention of Corneal Haze After Photo Therapeutic/Refractive Keratectomy (PTK/ PRK) and Collagen Cross Linking (CXL)

This is a investigator-initiated pilot clinical trial to ascertain the safety and efficacy of application of ex-vivo cultivated limbal stem cells in human eyes for treating Corneal Haze after Photo-Therapeutic/Refractive Keratectomy (PTK/ PRK) and Collagen Cross Linking (CXL). Instead of using adjunctive medical therapy like application of MMC (Mitomycin), a technique of cell delivery with fibrin sealant can be used. These cells are harvested from therapeutically accepted and serologically tested cadaveric corneas. The isolated limbal epithelial and mesenchymal or stromal cell suspension will then be cultured in CGMP laboratories and be tested for sterlity. These cells have also been shown to be effective in treating haze in laser refractive surgery in an animal model. Our initial experience of using these cells in a previous clinical trial showed that they were effective in preventing corneal haze in patients with burns and ulcers.

Study Overview

• Status: Unknown
• Conditions: Corneal Scars and Opacities
• Intervention / Treatment: Other: Vehicle; Biological: Stem cells

Detailed Description

In this pilot clinical trial, patients undergoing Photo Therapeutic/Refractive Keratectomy (PTK/ PRK) and Collagen Cross Linking (CXL), will be given human Limbus-derived Corneal Stem cells to assess the safety of these cells. Cells will be cultivated in a cGMP laboratory using standardized culture technique; from the limbal rims of cadaveric corneoscleral donor tissues that are therapeutically accepted and serologically tested. Briefly the limbal tissue will be cut up into small pieces and digested overnight using an enzyme (Collagenase L). The cells obtained from the digest will be cultured on a petri-dish using 2% serum and growth factors. A mixture of limbal epithelial cells and limbal stromal cells obtained from these cultures will be used in surgical procedures in a ratio of 2:1, after all the sterility checks. Mixed suspension of the limbal epithelial and the stromal cells at a concentration of 50000 cells/uL diluted in the thrombin component of fibrin sealant (TISEEL, Baxter) will be applied. The primary outcome measure is safety of this treatment and the secondary outcome measure is their efficacy that will be assessed at 1 month time points by (1) Clinical photography using a standard method where multiple blinded observers will grade the clinically apparent change in haze and (2) Objective quantification of the amount of light scattering using densitometry analysis function in Oculus Pentacam (OCULUS Optikgeräte GmbH).

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sayan Basu, MBBS MS; Phone Number: 2625 +9140 3061 2625; Email: sayanbasu@lvpei.org
• Study Contact Backup: Name: Pravin K Vaddavalli, MBBS MS; Phone Number: 2626 +91 40 3061 2626; Email: pravin@lvpei.org

Study Locations

• India
  • Telangana
    • Hyderabad, Telangana, India, 500034
      • Recruiting
      • LV Prasad Eye Institute
      • Contact: Sayan Basu, MBBS MS; Phone Number: 2625 +9140 3061 2625; Email: sayanbasu@lvpei.org
      • Contact: Vivek Singh, Msc PhD; Phone Number: 2286 +9140 3061 2286; Email: viveksingh@lvpei.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients between20 to 40 years of age
• Meeting standard selection criteria for bilateral PTK/PRK or CXL
• No systemic diseases
• Eligible to give informed consent
• No other ocular co-existing pathologies

Exclusion Criteria:

• Undergoing surgery in only one eye
• Grossly asymmetric pathology
• Refusal to give informed consent
• Not agreeable or uncooperative for corneal imaging
• Unlikely to come for follow-up for 1 month
• International and out-station patients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Standard Surgery with Vehicle; After the standard surgical procedure (PRK/PTK or CXL), patients will receive 50uL Fibrin Sealant (sham) without cells.	Other: Vehicle; 50uL of commercially available fibrin sealant (Baxter, TISEEL)
Experimental: Standard Surgery with Stem Cells; After the standard surgical procedure (PRK/PTK or CXL), patients will receive 50uL of a mixture of limbus derived corneal epithelial cells and limbus derived corneal stromal cells in a ratio of 2:1, at a concentration of 50000 cells/uL diluted in the thrombin component of Fibrin Sealant (TISEEL, Baxter).	Other: Vehicle; 50uL of commercially available fibrin sealant (Baxter, TISEEL); Biological: Stem cells; Mixture of limbus derived corneal epithelial cells and limbus derived corneal stromal cells in a ratio of 2:1, at a concentration of 50000 cells/uL diluted in fibrin sealant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maintenance of pre-operative best-spectacle corrected visual acuity	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy in reducing corneal light scatter using Scheimpflug imaging	Efficacy in reducing corneal light scatter using Scheimpflug imaging at 1 month by: Objective quantification of the amount of light scattering using densitometry analysis function in Oculus Pentacam (OCULUS Optikgeräte GmbH). • All routine clinical and imaging protocols performed for patients undergoing PTK/PRK and CXL will be diligently followed.	1 month

Collaborators and Investigators

• Sponsor: L.V. Prasad Eye Institute
• Investigators: Principal Investigator: Sayan Basu, MBBS MS, LV Prasad Eye Institute; Principal Investigator: Vivek Singh, MSc PhD, LV Prasad Eye Institute; Principal Investigator: Jagadesh C Reddy, MBBS MD, LV Prasad Eye Institute; Principal Investigator: Pratik Gogri, MBBS MS, LV Prasad Eye Institute

Publications and helpful links

General Publications

• Basu S, Hertsenberg AJ, Funderburgh ML, Burrow MK, Mann MM, Du Y, Lathrop KL, Syed-Picard FN, Adams SM, Birk DE, Funderburgh JL. Human limbal biopsy-derived stromal stem cells prevent corneal scarring. Sci Transl Med. 2014 Dec 10;6(266):266ra172. doi: 10.1126/scitranslmed.3009644.
• Basu S, Damala M, Singh V. Limbal Stromal Stem Cell Therapy for Acute and Chronic Superficial Corneal Pathologies: Early Clinical Outcomes of The Funderburgh Technique. Investigative Ophthalmology & Visual Science. 2017 Jun 23;58(8):3371-337

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2017
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): June 1, 2020

Study Registration Dates

• First Submitted: August 19, 2017
• First Submitted That Met QC Criteria: September 21, 2017
• First Posted (Actual): September 27, 2017

Study Record Updates

• Last Update Posted (Actual): February 26, 2019
• Last Update Submitted That Met QC Criteria: February 25, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Stem Cell Therapy; Phototherapeutic Keratectomy (PTK); photorefractive Keratectomy (PRK); Collagen Cross-linking (CXL)
• Additional Relevant MeSH Terms: Nervous System Diseases; Eye Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Corneal Diseases; Facial Injuries; Eye Injuries; Corneal Injuries
• Other Study ID Numbers: LEC 07-17-068

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No