Limbus-derived Stem Cells for Prevention of Postoperative Corneal Haze

Corneal Scars and Opacities Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03295292
• Other study ID #: LEC 07-17-068
• Status: Recruiting
• Phase: Phase 1
• Start date: August 1, 2017
• Est. completion date: June 2020

Study information

• Verified date: February 2019
• Source: L.V. Prasad Eye Institute
• Contact: Sayan Basu, MBBS MS
• Phone: +9140 3061 2625
• Email: sayanbasu[@]lvpei.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: June 2020
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Corneal Injuries
• Corneal Opacity
• Corneal Scars and Opacities

Intervention

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

Other:
• Vehicle
50uL of commercially available fibrin sealant (Baxter, TISEEL)

Locations

Country	Name	City	State
India	LV Prasad Eye Institute	Hyderabad	Telangana

Sponsors (1)

Lead Sponsor	Collaborator
L.V. Prasad Eye Institute

Country where clinical trial is conducted

India, 

References & Publications (2)

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

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maintenance of pre-operative best-spectacle corrected visual acuity		1 month
Secondary	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