Corneal Scars and OpacitiesEarly Phase 1NCT04932629
To Evaluate the Clinical Safety and Efficacy of Limbal Stem Cell for Treatment of Superficial Corneal Pathologies".
A Early Phase 1 study testing Ex-vivo cultivated Allogeneic limbal stromal stem cells in people with Corneal Scars and Opacities, run by L.V. Prasad Eye Institute.
Trial summary
This study proposes to investigate the transplantation of ex-vivo cultivated allogenic limbal stromal cells for the treatment of the corneal pathologies. The limbus is an ideal source as the stem cells are numerous and located very superficially in the tissue (17). Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Corneal Scars and Opacities
- What is being tested?
- Ex-vivo cultivated Allogeneic limbal stromal stem cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- No sites listed yet
- Study dates
- Jul 2021to Jan 2023
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Male and female participants who are ≥18 and ≤ 60 years of age.
- Patients having unilateral superficial corneal pathologies (defined as involving the anterior 200µM of the corneal stroma on ASOCT imaging)
- Corneal burns, ulcers and scars
- No prior history of corneal transplantation
- No ongoing and other active ocular pathology
- Candidate for stem cell transplant
- No severe pathological and psychological conditions that might interfere with the patient's participation in the study
- Able to provide written and audio-visual informed consent prior to any study specific screening procedures with the understanding that the patient has the right to withdraw from the study at any time, for any reason without prejudice
Who cannot join
- Bilateral corneal disease,
- Corneal scars with limbal dysfunction (clinically defined as absent limbal palisades or conjunctivalization of the cornea)
- Ocular surface disease including dry eye disease (defined as a Schirmer's test of less than 10mm at 5 minutes),
- Unknown etiology, post-herpetic eye disease or eyes with active intra-ocular inflammation,
- Children (<18 years of age),
- Less than 3 months after documented clinical resolution of acute disease
Show all 13Show fewer
- Inability/refusal to give written informed consent
- Undergo any of the anterior segment imaging tests.
- Patient should have not participated in another clinical study within 30 days of their enrolment on this study.
- History or evidence of cardiac disease: congestive heart failure; New York Heart Association (NYHA) class 2 or greater (see Appendix 6); active coronary artery disease; unstable angina, cardiac arrhythmias requiring anti-arrhythmic therapy, atrio-ventricular block of second or third degree, or uncontrolled hypertension, patients with recent (less than 6 months) myocardial infarction (MI) or coronary revascularization.
- Pregnant and lactating patients, positive urine pregnancy test in women of childbearing potential
- Reproductive age patients not practicing effective and adequate birth control measures
- Previous participation in this study
Trial locations and contacts
No sites are listed yet.
About this study
Official title: A Proof of Concept Study to Evaluate the Clinical Safety and Efficacy of Ex-vivo Cultivated Allogenic Limbal Stem Cell Transplantation for Treatment of Superficial Corneal Pathologies".
This study proposes to investigate the transplantation of ex-vivo cultivated allogenic limbal stromal cells for the treatment of the corneal pathologies. The limbus is an ideal source as the stem cells are numerous and located very superficially in the tissue (17). Pre-clinical work suggests human corneal stromal stem cells can be isolated from the cadaveric tissues, cultivated in conditions suitable for cell based therapy and used to prevent fibrosis in a murine model of corneal stromal scarring. Further, these cells are able to successfully engraft, differentiate, and mediate wound healing in the corneal stroma such that the tissue remains healthy, free of fibrotic tissue, and optically transparent. The clinical implications of these findings are substantial in that it represents the potential to lessen the burden on donor tissue necessary for corneal allografts by using cultured cells to regenerate tissue. We foresee the ability of a clinician to and grow and expand the cells in number and after surgically removing the scar tissue from the wounded eye, apply the cultured limbal stem cells to regenerate healthy, transparent tissue.
Read the detailed description
This would be a single-center prospective, open labeled, non-randomized interventional study. This study is an Investigator Initiated Study (IIS). The Ethics Committee of the LV Prasad Eye Institute, Hyderabad, would prospectively approve this study. This study would be conducted in strict adherence to the tenets of the Declaration of Helsinki, ICH GCP E6 (R2), Indian GCP Guidelines and New Drugs and Clinical Trial Rules 2019 and associated amendments and current National Ethical Guidelines for Biomedical and Health Research Involving Human Participants and Current National Stem Cell Research Guidelines and New Drugs and Clinical Trial Rules 2019.
Once the participants are found to be suitable for limbal transplant surgery, the patients will be administered written informed consent and audio /visual consent as per regulations. Detailed ophthalmic examination will be done to ensure that the patient is eligible for the trial.
All the screening procedures will be accomplished within 14± 7days. On Day 0 that is the date of surgery a Unique Participant Identification Number (UPIN) will be assigned to each patient and it would be in addition to hospital medical record number. The surgery will be done under local or general anesthesia (depending on age and patient preference).
In this prospective interventional study patients with unilateral superficial corneal scars 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 eligible patients will undergo corneal transplant surgery, when the central corneal epithelium will be removed using a surgical sponge. 0.1ml of stromal cells in a concentration of 0.5x106 cells/µl 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 30, Day 90, Day 180 and Day 360 and 720 Days post-surgery. The primary outcome measure of this study is to note any ocular or systemic adverse effects of this intervention at the various post-operative time points. The secondary outcome measures are visual improvement and change in the density and appearance of the corneal scarring and other pathologies after treatment.
- Conditions
- Corneal Scars and Opacities
- Being tested
- Ex-vivo cultivated Allogeneic limbal stromal stem cells
- Medical subject headings
- Corneal Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ex-vivo cultivated Allogeneic limbal stromal stem cellsBiological
n this prospective intervention study patients with unilateral superficial corneal scars will undergo a surgical procedure and in the second procedure, the eligible patients will undergo corneal transplant surgery, when the central corneal epithelium will be removed using a surgical sponge. 0.1ml of stromal cells in a concentration of 0.5x10*6 cells/µl 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 30, Day 90, Day 180 and Day 360 and 720 Days post-surgery
| Study group | Role | What they receive |
|---|---|---|
| Experimental Group | Experimental | The eligible patients will undergo corneal transplant surgery, when the central corneal epithelium will be removed using a surgical sponge. 0.1ml of stromal cells in a concentration of 0.5x106 cells/µl diluted in the thrombin component of fibrin glue (TISEEL, Baxter) will be applied to the debrided corneal stroma. Receives: Biological: Ex-vivo cultivated Allogeneic limbal stromal stem cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measurement of any ocular or systemic adverse effects
The primary outcome measure of this study is to note any ocular or systemic adverse effects
Measured: Day 90 post-surgery
Secondary outcomes (2)
Measurement of Visual improvement
Visual improvement using ETDRS vision chart method where visual acuity is the measurement, Changes in ETDRS score is a scale and ETDRS letter score will be measure in log units
Measured: Day 720 post surgery
Change in Corneal light scattering
Change in Corneal light scattering using Scheimpflug imaging where Corneal light scattering is the measurement, Corneal Densitometry measurements is a scale and expressed in standardized grayscale units (GSU).
Measured: Day 720 post surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2021
- Study startJul 2021 (estimated)
- Primary completionDec 2021 (estimated)
- Study completionJan 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Corneal Scars and OpacitiesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- L.V. Prasad Eye Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Vivek Singh, L.V. Prasad Eye Institute
- Investigators
- Dr.Vivek Singh, PhD, Principal investigator, LV Prasad Eye Institute (Hyderabad Eye Research Foundation)Dr.Sayan Basu, MBBS.MS, Principal investigator, LV Prasad Eye Institute (Hyderabad Eye Research Foundation)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04932629
- Sponsor's protocol ID
- HERF-SSC-SCP-01
- Status last verified
- Jun 2021
- First submitted
- 17 Feb 2021
- Last updated
- 21 Jun 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 25504883Basu 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
Funderburgh, J., Basu, S., Damala, M., Tavakkoli, F., Sangwan, V., & Singh, V. (2018). Limbal stromal stem cell therapy for acute and chronic superficial corneal pathologies: one-year outcomes. Investigative Ophthalmology & Visual Science, 59(9), 3455-3455
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Proof of Concept Study to Evaluate the Clinical Safety and Efficacy of Ex-vivo Cultivated Allogenic Limbal Stem Cell Transplantation for Treatment of Superficial Corneal Pathologies".
- ClinicalTrials.gov ID
- NCT04932629
- Acronym / sponsor ID
- HERF-SSC-SCP-01
- Conditions
- Corneal Scars and Opacities
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- L.V. Prasad Eye InstituteUniversity, hospital or other
- Study start
- Jul 2021 (estimated)
- Primary completion
- Dec 2021 (estimated)
- Study completion
- Jan 2023 (estimated)
- First posted
- 21 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study proposes to investigate the transplantation of ex-vivo cultivated allogenic limbal stromal cells for the treatment of the corneal pathologies. The limbus is an ideal source as the stem cells are numerous and located very superficially in the tissue (17). Pre-clinical work suggests human corneal stromal stem cells can be isolated from the cadaveric tissues, cultivated in conditions suitable for cell based therapy and used to prevent fibrosis in a murine model of corneal stromal scarring. Further, these cells are able to successfully engraft, differentiate, and mediate wound healing in the corneal stroma such that the tissue remains healthy, free of fibrotic tissue, and optically transparent. The clinical implications of these findings are substantial in that it represents the potential to lessen the burden on donor tissue necessary for corneal allografts by using cultured cells to regenerate tissue. We foresee the ability of a clinician to and grow and expand the cells in number and after surgically removing the scar tissue from the wounded eye, apply the cultured limbal stem cells to regenerate healthy, transparent tissue.
Detailed description
This would be a single-center prospective, open labeled, non-randomized interventional study. This study is an Investigator Initiated Study (IIS). The Ethics Committee of the LV Prasad Eye Institute, Hyderabad, would prospectively approve this study. This study would be conducted in strict adherence to the tenets of the Declaration of Helsinki, ICH GCP E6 (R2), Indian GCP Guidelines and New Drugs and Clinical Trial Rules 2019 and associated amendments and current National Ethical Guidelines for Biomedical and Health Research Involving Human Participants and Current National Stem Cell Research Guidelines and New Drugs and Clinical Trial Rules 2019.
Once the participants are found to be suitable for limbal transplant surgery, the patients will be administered written informed consent and audio /visual consent as per regulations. Detailed ophthalmic examination will be done to ensure that the patient is eligible for the trial.
All the screening procedures will be accomplished within 14± 7days. On Day 0 that is the date of surgery a Unique Participant Identification Number (UPIN) will be assigned to each patient and it would be in addition to hospital medical record number. The surgery will be done under local or general anesthesia (depending on age and patient preference).
In this prospective interventional study patients with unilateral superficial corneal scars 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 eligible patients will undergo corneal transplant surgery, when the central corneal epithelium will be removed using a surgical sponge. 0.1ml of stromal cells in a concentration of 0.5x106 cells/µl 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 30, Day 90, Day 180 and Day 360 and 720 Days post-surgery. The primary outcome measure of this study is to note any ocular or systemic adverse effects of this intervention at the various post-operative time points. The secondary outcome measures are visual improvement and change in the density and appearance of the corneal scarring and other pathologies after treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental Group | Experimental | Biological: Ex-vivo cultivated Allogeneic limbal stromal stem cellsThe eligible patients will undergo corneal transplant surgery, when the central corneal epithelium will be removed using a surgical sponge. 0.1ml of stromal cells in a concentration of 0.5x106 cells/µl diluted in the thrombin component of fibrin glue (TISEEL, Baxter) will be applied to the debrided corneal stroma. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Male and female participants who are ≥18 and ≤ 60 years of age.
- Patients having unilateral superficial corneal pathologies (defined as involving the anterior 200µM of the corneal stroma on ASOCT imaging)
- Corneal burns, ulcers and scars
- No prior history of corneal transplantation
- No ongoing and other active ocular pathology
Key exclusion criteria (13 listed)
- Bilateral corneal disease,
- Corneal scars with limbal dysfunction (clinically defined as absent limbal palisades or conjunctivalization of the cornea)
- Ocular surface disease including dry eye disease (defined as a Schirmer's test of less than 10mm at 5 minutes),
- Unknown etiology, post-herpetic eye disease or eyes with active intra-ocular inflammation,
- Children (<18 years of age),
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ex-vivo cultivated Allogeneic limbal stromal stem cellsn this prospective intervention study patients with unilateral superficial corneal scars will undergo a surgical procedure and in the second procedure, the eligible patients will undergo corneal transplant surgery, when the central corneal epithelium will be removed using a surgical sponge. 0.1ml of stromal cells in a concentration of 0.5x10*6 cells/µl 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 30, Day 90, Day 180 and Day 360 and 720 Days post-surgery | Biological | Experimental Group |
Primary outcome
Measurement of any ocular or systemic adverse effects
Time frame: Day 90 post-surgery
The primary outcome measure of this study is to note any ocular or systemic adverse effects
2 secondary outcomes
Measurement of Visual improvement
Time frame: Day 720 post surgery
Change in Corneal light scattering
Time frame: Day 720 post surgery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2021.
- Background: PubMed 25504883Basu 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.
- Results publicationBasu 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
- Results publicationFunderburgh, J., Basu, S., Damala, M., Tavakkoli, F., Sangwan, V., & Singh, V. (2018). Limbal stromal stem cell therapy for acute and chronic superficial corneal pathologies: one-year outcomes. Investigative Ophthalmology & Visual Science, 59(9), 3455-3455
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dr.Vivek Singh, PhD principal investigator
LV Prasad Eye Institute (Hyderabad Eye Research Foundation)
Dr.Sayan Basu, MBBS.MS principal investigator
LV Prasad Eye Institute (Hyderabad Eye Research Foundation)
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Ex-vivo cultivated Allogeneic limbal stromal stem cells in people with Corneal Scars and Opacities, run by L.V. Prasad Eye Institute.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Dr.Sayan Basu, MBBS,MS (040-68102534, sayanbasu@lvpei.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measurement of any ocular or systemic adverse effects (time frame: Day 90 post-surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04932629, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jun 2021.