Stem Cells Therapy for Corneal Blindness (ExCell)

Ex-vivo Cultivated Limbal Stem Cell Transplantation for Treatment of Superficial Corneal Pathologies

This is a investigative initiated, comparative pilot clinical trial to ascertain the safety of application of ex-vivo cultivated limbal stem cells in human eyes for treating different superficial corneal pathologies. Pre-clinical work in murine models have already demonstrated efficacy of this technique in curing murine corneal pathologies.

Study Overview

• Status: Unknown
• Conditions: Corneal Injuries; Corneal Scars and Opacities; Corneal Burns
• Intervention / Treatment: Biological: Ex-vivo cultivated limbal stem cell pool

Detailed Description

In this prospective interventional study patients with superficial corneal pathologies like scars, ulcers and burns will undergo a surgical procedure. Limbal ring from a cadaveric donor tissue, which is therapeutically accepted and serologically tested, is collected. This tissue will then be cultivated in the stem cell biology laboratory using standardized culture technique. 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. The cultured cells will be passaged three times to remove all epithelial cells from the culture. In the second procedure, the central corneal epithelium will be removed using a surgical sponge. 0.1ml of stromal cells in a concentration of 5x10^3 cells/uL diluted in the thrombin component of fibrin glue (TISEEL, Baxter) will be applied to the debrided corneal stroma. A soft bandage contact lens will be placed over the cornea at the end of the procedure. The patient will receive topical antibiotic and steroid eye drops in the post-operative period. Periodic comprehensive ophthalmic evaluation along with anterior segment optical coherence tomography (ASOCT) scanning and slit-lamp photography will be done at day 1, day 7, day 45 and day 90.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sayan Basu, MBBS, MS; Phone Number: 2625 9140-30612625; Email: sayanbasu@lvpei.org
• Study Contact Backup: Name: Vivek Singh, MSc PhD; Phone Number: 2286 9140-30612286; Email: viveksingh@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 Singh, MSc PhD; Phone Number: 2286 +9140 3061 2286; Email: viveksingh@lvpei.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male and Female participants who are aged between 18-60 years.
2. Patients who are having with unilateral blindness due to superficial (defined as involving the anterior 200 microns of the corneal stroma on ASOCT imaging) corneal wounds, ulcers, burns and scars.
3. Eyes with otherwise normal.

Exclusion Criteria:

1. Active infection, proven by microbiology.
2. Unknown etiology, post-herpetic eye disease or eyes with active intra-ocular inflammation.
3. Children (<18 years of age).
4. Inability/refusal to give written informed consent or to undergo any of the anterior segment imaging tests.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard Surgical therapy; Includes the control group that fulfills the inclusion criteria
Active Comparator: Ex-vivo cultivated limbal stem cell pool; 0.5 million stromal and epithelial cells will be incorporated in 0.05ml of commercially available fibrin glue and pasted over the corneal lesion after epithelial debridement.	Biological: Ex-vivo cultivated limbal stem cell pool; 0.5 million stromal and epithelial cells will be incorporated in 0.05ml of commercially available fibrin glue and pasted over the corneal lesion after epithelial debridement.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Ocular or systemic adverse effects	until 3months after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual improvement after treatment.	Checking for the improvement in visual acuity that will be calculated using LogMAR chart (where 20/20 vision is normal).	until 3months after surgery

Collaborators and Investigators

• Sponsor: L.V. Prasad Eye Institute
• Investigators: Principal Investigator: Sayan Basu, MBBS, MS, LV Prasad Eye Institiute; Principal Investigator: Vivek Singh, MSc PhD, LV Prasad Eye Institiute

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 31, 2016
• Primary Completion (Anticipated): February 1, 2019
• Study Completion (Anticipated): August 1, 2019

Study Registration Dates

• First Submitted: October 20, 2016
• First Submitted That Met QC Criteria: October 26, 2016
• First Posted (Estimate): October 28, 2016

Study Record Updates

• Last Update Posted (Actual): March 6, 2018
• Last Update Submitted That Met QC Criteria: March 3, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• 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: LVPEI-2014-1 Version 1 15Jan14

Plan for Individual participant data (IPD)

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