Clinical trial NCT06700655: A Clinical Study on Co-transplantation of Autologous Limbal Stem Cells and Corneal Stromal Stem Cells to Repair Corneal Injury
Official title: A Clinical Study on Co-transplantation of Autologous Limbal Stem Cells and Corneal Stromal Stem Cells to Repair Corneal Injury: an Open-label, Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Limbal Stem Cells Deficiency
Keywords: Limbal stem cell
Limbal stem cells deficiency
Corneal stromal stem cells
Corneal transplantation
Lead sponsor: Zhongshan Ophthalmic Center, Sun Yat-sen University
Sponsor class: OTHER
First posted: 2024-11-22
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study aims to: 1) verify the feasibility of treating limbal stem cell deficiency (LSCD) caused by chemical injury with autologous limbal stem cell transplantation combined with corneal stromal stem cell transplantation; 2) evaluate the corneal healing patterns following autologous stem cell transplantation; and 3) establish a clinical intervention protocol based on autologous corneal stem cell transplantation. Sixty cases of single-eye LSCD were included.

Detailed description: Limbal Stem Cells (LSCs) are the sole source of corneal epithelial self-renewal and play a critical role in maintaining corneal transparency. Chemical or physical injury to the eye and inflammation can lead to limbal stem cell deficiency (LSCD), accompanied by a series of pathological changes, such as irreversible fibrosis of corneal stromal cells and neovascularization, ultimately resulting in blindness. The fundamental solution for such diseases is the replenishment of LSCs to reconstruct a functional cornea. However, traditional treatment methods, such as corneal transplantation, face bottlenecks, including a severe shortage of corneal donors and the risk of immune rejection. Additionally, donor corneas do not contain LSCs, making it impossible to reconstruct the patient's limbal region, resulting in poor long-term efficacy.

In 2015, autologous LSCs were approved by the European Union as a commercial stem cell product for treating patients with chemically induced LSCD. However, LSCD patients are often accompanied by damage to the corneal stroma; while LSC transplantation can restore the limbal region and corneal epithelium, it cannot repair stromal opacities. Research indicates that transplantation of corneal stromal stem cells can reconstruct organized collagen structures and restore stromal transparency. Over the past decade, clinical studies using LSCs and corneal stromal stem cells to treat LSCD patients have been conducted in multiple countries, demonstrating the safety and efficacy of these stem cell therapies for corneal blindness.

Based on these findings above, the investigators have established a serum-free, carrier-free culture system that enables efficient and uniform in vitro expansion of functional LSCs and corneal stromal stem cells. By obtaining a 2 x 5 mm limbal tissue sample from the healthy eye of the patient, the investigators can acquire a sufficient number of cells for transplantation. Preclinical studies have confirmed that the expanded cells are effective and safe for treating LSCD animal models. This study aims to use autologous LSCs combined with corneal stromal stem cell transplantation to treat patients with unilateral LSCD, restoring their corneal transparency and visual function. This approach provides a novel treatment method for patients and promotes the application of stem cell regenerative medicine for the treatment of corneal blindness in China.

Eligibility criteria: Inclusion Criteria:

* Chemical injury from acid or alkali exposure
* Extensive limbal stem cell deficiency (greater than 180 degrees), with corneal stromal opacity not exceeding a depth of 250 μm
* Corneal epithelial conjunctivalization and fibrosis, with neovascularization extending into more than half of the quadrants
* Unilateral ocular involvement, with normal limbal stem cell function in the contralateral healthy eye
* No significant improvement in ocular surface signs and symptoms after pharmacological or surgical interventions, stable for over three months

Exclusion Criteria:

* Bilateral corneal stem cell deficiency, such as in Stevens-Johnson syndrome, ocular cicatricial pemphigoid, or congenital aniridia
* Subclinical limbal stem cell deficiency in the contralateral eye
* Signs of corneal endothelial decompensation, such as corneal bullae or corneal edema
* Presence of infectious inflammation on the ocular surface
* Severe dry eye
* Eyelid abnormalities requiring corrective surgery to restore normal anatomical structure
* Presence of chronic dacryocystitis, cataracts, uveitis, diabetic retinopathy, retinal detachment, or other ocular diseases
* Patients who have undergone cataract surgery or other intraocular procedures
* Glaucoma patients requiring long-term topical ocular medications
* History of corneal perforation in the affected eye
* Severe primary cardiovascular, hepatic, renal, endocrine, or hematologic disorders, diabetes, or immune deficiency in the medical history
* Pregnant or lactating women
* Positive screening for infectious diseases (HIV, HBV, HTLV, EBV, CMV, or syphilis)
* Other vision-impairing diseases present
* Allergy to bovine serum products
* History of multiple drug allergies or hypersensitive constitution
* Concurrent participation in other drug clinical trials
* History of mental health disorders affecting the ability to comply with study requirements
* Judged unsuitable for participation by the investigator

Primary outcomes:
measure: Vision
timeFrame: [set the tissue sampling date at the begin] Enrollment, before the transplantation, First follow-up (Day 32), Second follow-up (Day 48), Third follow-up (Day 108), Fourth follow-up (6 months), Fifth follow-up (1 year), Sixth follow-up (2 years)
Secondary outcomes:
measure: Efficacy Scoring
timeFrame: [set the corneal limbal tissue sampling date at the begin] First follow-up (Day 32), Second follow-up (Day 48), Third follow-up (Day 108), Fourth follow-up (6 months), Fifth follow-up (1 year), Sixth follow-up (2 years)
measure: Ocular adverse event evaluation
timeFrame: [set the corneal limbal tissue sampling date at the begin] before the transplantation, First follow-up (Day 32), Second follow-up (Day 48), Third follow-up (Day 108), Fourth follow-up (6 months), Fifth follow-up (1 year), Sixth follow-up (2 years)
measure: ophthalmic examination（slit-lamp）
timeFrame: [set the tissue sampling date at the begin] Enrollment, before the transplantation, First follow-up (Day 32), Second follow-up (Day 48), Third follow-up (Day 108), Fourth follow-up (6 months), Fifth follow-up (1 year), Sixth follow-up (2 years)
measure: cornea confocal
timeFrame: [set the tissue sampling date at the begin] Enrollment, before the transplantation, Second follow-up (Day 48), Third follow-up (Day 108), Fourth follow-up (6 months), Fifth follow-up (1 year), Sixth follow-up (2 years)
measure: corneal topography
timeFrame: [set the tissue sampling date at the begin] Enrollment, before the transplantation, First follow-up (Day 32), Second follow-up (Day 48), Third follow-up (Day 108), Fourth follow-up (6 months), Fifth follow-up (1 year), Sixth follow-up (2 years)
measure: Optical Coherence Tomography
timeFrame: [set the tissue sampling date at the begin] Enrollment, before the transplantation, First follow-up (Day 32), Second follow-up (Day 48), Third follow-up (Day 108), Fourth follow-up (6 months), Fifth follow-up (1 year), Sixth follow-up (2 years)
measure: anterior segment photography
timeFrame: [set the tissue sampling date at the begin] Enrollment, before the transplantation, First follow-up (Day 32), Second follow-up (Day 48), Third follow-up (Day 108), Fourth follow-up (6 months), Fifth follow-up (1 year), Sixth follow-up (2 years)
measure: VFQ-25 questionnaire
timeFrame: [set the tissue sampling date at the begin] Enrollment, before the transplantation, Second follow-up (Day 48), Third follow-up (Day 108), Fourth follow-up (6 months), Fifth follow-up (1 year), Sixth follow-up (2 years)
Other outcomes:
measure: Lung Condition
timeFrame: [set the tissue sampling date at the begin] Enrollment, Sixth follow-up (2 years)
measure: Cardiac Function
timeFrame: [set the tissue sampling date at the begin] Enrollment, Sixth follow-up (2 years)
measure: Number of participants with abnormal hematologic parameters as assessed by standard criteria (the normal scale on the report)
timeFrame: [set the tissue sampling date at the begin] Enrollment, before the transplantation, Second follow-up (Day 48), Third follow-up (Day 108), Fifth follow-up (1 year), Sixth follow-up (2 years)
measure: urine test
timeFrame: [set the tissue sampling date at the begin] Enrollment, First follow-up (Day 32), Fifth follow-up (1 year), Sixth follow-up (2 years)
measure: Head abnormalities in general physical condition as assessed by clinical examination
timeFrame: [set the tissue sampling date at the begin] Enrollment, First follow-up (Day 32), Fifth follow-up (1 year), Sixth follow-up (2 years)
measure: Neck abnormalities in general physical condition as assessed by clinical examination
timeFrame: [set the tissue sampling date at the begin] Enrollment, First follow-up (Day 32), Fifth follow-up (1 year), Sixth follow-up (2 years)
measure: Lymph Node abnormalities in general physical condition as assessed by clinical examination
timeFrame: [set the tissue sampling date at the begin] Enrollment, First follow-up (Day 32), Fifth follow-up (1 year), Sixth follow-up (2 years)
measure: Spinal and Limb abnormalities in general physical condition as assessed by clinical examination
timeFrame: [set the tissue sampling date at the begin] Enrollment, First follow-up (Day 32), Fifth follow-up (1 year), Sixth follow-up (2 years)
measure: Abdominal abnormalities in general physical condition as assessed by clinical examination
timeFrame: [set the tissue sampling date at the begin] Enrollment, First follow-up (Day 32), Fifth follow-up (1 year), Sixth follow-up (2 years)
measure: Neurological abnormalities in general physical condition as assessed by clinical examination
timeFrame: [set the tissue sampling date at the begin] Enrollment, First follow-up (Day 32), Fifth follow-up (1 year), Sixth follow-up (2 years)
measure: Skin abnormalities in general physical condition as assessed by clinical examination
timeFrame: [set the tissue sampling date at the begin] Enrollment, First follow-up (Day 32), Fifth follow-up (1 year), Sixth follow-up (2 years)
Locations:
Study officials:
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