Limbus-derived Stem Cells for Prevention of Postoperative Corneal Haze

NCT ID: NCT03295292

Last Updated: 2019-02-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-01
• Study Completion Date: 2020-06-30

Brief 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.

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).

Conditions

Corneal Scars and Opacities

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Standard Surgery with Vehicle

After the standard surgical procedure (PRK/PTK or CXL), patients will receive 50uL Fibrin Sealant (sham) without cells.

Group Type: SHAM_COMPARATOR

Vehicle

Intervention Type: OTHER

50uL of commercially available fibrin sealant (Baxter, TISEEL)

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).

Group Type: EXPERIMENTAL

Stem cells

Intervention Type: BIOLOGICAL

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

Vehicle

Intervention Type: OTHER

50uL of commercially available fibrin sealant (Baxter, TISEEL)

Interventions

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

Intervention Type: BIOLOGICAL

Vehicle

50uL of commercially available fibrin sealant (Baxter, TISEEL)

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

L.V. Prasad Eye Institute

OTHER

Sponsor Role: lead

Responsible Party

Vivek Singh

Prinicipal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sayan Basu, MBBS MS

Role: PRINCIPAL_INVESTIGATOR

LV Prasad Eye Institute

Vivek Singh, MSc PhD

Role: PRINCIPAL_INVESTIGATOR

LV Prasad Eye Institute

Jagadesh C Reddy, MBBS MD

Role: PRINCIPAL_INVESTIGATOR

LV Prasad Eye Institute

Pratik Gogri, MBBS MS

Role: PRINCIPAL_INVESTIGATOR

LV Prasad Eye Institute

Locations

LV Prasad Eye Institute

Hyderabad, Telangana, India

Site Status: RECRUITING

Countries

India

Central Contacts

Sayan Basu, MBBS MS

Role: CONTACT

sayanbasu@lvpei.org

+9140 3061 2625 ext. 2625

Pravin K Vaddavalli, MBBS MS

Role: CONTACT

pravin@lvpei.org

+91 40 3061 2626 ext. 2626

Facility Contacts

Sayan Basu, MBBS MS

Role: primary

sayanbasu@lvpei.org

+9140 3061 2625 ext. 2625

Vivek Singh, Msc PhD

Role: backup

viveksingh@lvpei.org

+9140 3061 2286 ext. 2286

References

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.

Reference Type: RESULT

PMID: 25504883 (View on PubMed)

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

Reference Type: RESULT

Other Identifiers

LEC 07-17-068

Identifier Type: -

Identifier Source: org_study_id