Limbal Stem-cell DeficiencyCLET-4-LSCDNCT03884569
Cultivated Limbal Epithelial Transplantation (CLET) for Limbal Stem Cell Deficiency (LSCD)
An observational study of Limbal Stem-cell Deficiency, run by Instituto Universitario de Oftalmobiología Aplicada (Institute of Applied Ophthalmobiology) - IOBA at 1 site in Spain.
Trial summary
CLET is a published treatment for the management of corneal failure due to extensive LSCD. Due to our previous studies on this novel treatment, the regulatory agency of Spain "Agencia Española de Medicamentos y Productos Sanitarios (AEMPS)" authorized our institution (IOBA-University of Valladolid) to perform this… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Limbal Stem-cell Deficiency
- How many people
- 30 participants
- Where
- 1 siteSpain
- Study dates
- Nov 2025to 31 Dec 2025
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients diagnosed with corneal failure due to LSCD who accept and sign the informed written consent treatment to be treated with CLET
Total and/or severe LSCD of any etiology in one or both eyes.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Spain1 site
IOBA
Valladolid, 47011
Margarita Calonge, MD, PhD
Margarita Calonge, MD, PhD
About this study
Official title: Cultivated Limbal Epithelial Transplantation (CLET) for Limbal Stem Cell Deficiency (LSCD): an Observational Study on Safety and Effectiveness
CLET is a published treatment for the management of corneal failure due to extensive LSCD. Due to our previous studies on this novel treatment, the regulatory agency of Spain "Agencia Española de Medicamentos y Productos Sanitarios (AEMPS)" authorized our institution (IOBA-University of Valladolid) to perform this kind of therapy (CLET) in a case-by-case base following the Special Situation Medicines Policy Procedure in Spain. Upon approval of the permanent authorization patients will be included as specified by AEMPS.The objective of this study is to perform a protocolized treatment and follow up so that results can be reported to the scientific community.
- Conditions
- Limbal Stem-cell Deficiency
- Keywords
- limbal stem cell deficiency, corneal failure, limbal epithelial stem cells, ocular surface, corneal blindness
- Medical subject headings
- Limbal Stem Cell Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Patients treated with CLET | Previously treated with CLET patients are included retrospectively, as the follow-up procedure is already stablished in our centre, and patients treated following standard care or through "drugs-in-special-situation" request in Spain prospectively. Patients are not treated to be included in the study, only the follow-up variables are taken into account. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Points of improvement in the Single Item Dry Eye Questionnaire (SIDEQ)
The SIDEQ gives a 0-4 score about the presence of dryness, foreign body sensation, burning/stinging, pain, itching, sensitivity to light, and blurred vision, where higher scores indicate higher intensity of the symptom (maximun score: 28). One of the primary outcomes for this work is the improvement in any of the four questionnaires shown here.
Measured: 6 months
Points of improvement about the Ocular Surface Disease Index (OSDI)
The OSDI evaluates ocular surface symptoms with 12 questions, and scores >12 indicate abnormal symptomatology, and >32 means severe symptoms (maximum score 100). One of the primary outcomes for this work is the improvement in any of the four questionnaires shown here.
Measured: 6 months
Points of improvement in the National Eye Institute 25-item Visual Function Questionnaire (NEI-VFQ25)
The visual function-related aspects of the quality of life were evaluated with the NEI-VFQ25, where higher scores on a 0 to 100 scale indicate better function. One of the primary outcomes for this work is the improvement in any of the four questionnaires shown here.
Measured: 6 months
Points of improvement in the Change in Dry Eye Symptoms Questionnaire (CDES-Q)
The CDES-Q evaluates ocular surface symptoms with two questions, CDES-Q1 and CDES-Q2. CDES-Q1 evaluates the change in symptoms occured since the previous examination (same, better or worse). CDES-Q2 evaluates the magnitude of the change in a scale from 0 to 10, where 0 means "slightly better/worse" and 10 means "extremely better/worse". One of the primary outcomes for this work is the improvement in any of the four questionnaires shown here.
Measured: 6 months
Percentage of improvement in corneal conjunctivalization
Percentage of corneal area with conjunctivalization (superficial opacity and/or superficial neovascularization) will be measured.
Measured: 6 months
Complete absence of persistent epithelial defects
Corneal fluorescein staining has to rule out epithelial breakdown
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2019
- Study startNov 2025 (estimated)
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Limbal Stem-cell DeficiencyStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Instituto Universitario de Oftalmobiología Aplicada (Institute of Applied Ophthalmobiology) - IOBA
- Sponsor type
- University, hospital or other
- Collaborators
- Citospin, Red de Terapia Celular, University of Valladolid
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03884569
- Sponsor's protocol ID
- IOBA201901
- Acronym
- CLET-4-LSCD
- Status last verified
- May 2025
- First submitted
- 8 Mar 2019
- Last updated
- 16 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Calonge M, Perez I, Galindo S, Nieto-Miguel T, Lopez-Paniagua M, Fernandez I, Alberca M, Garcia-Sancho J, Sanchez A, Herreras JM. A proof-of-concept clinical trial using mesenchymal stem cells for the treatment of corneal epithelial stem cell deficiency. Transl Res. 2019 Apr;206:18-40. doi: 10.1016/j.trsl.2018.11.003. Epub 2018 Nov 22.
PubMed 30578758Galindo S, Herreras JM, Lopez-Paniagua M, Rey E, de la Mata A, Plata-Cordero M, Calonge M, Nieto-Miguel T. Therapeutic Effect of Human Adipose Tissue-Derived Mesenchymal Stem Cells in Experimental Corneal Failure Due to Limbal Stem Cell Niche Damage. Stem Cells. 2017 Oct;35(10):2160-2174. doi: 10.1002/stem.2672. Epub 2017 Aug 10.
PubMed 28758321Lopez-Paniagua M, Nieto-Miguel T, de la Mata A, Galindo S, Herreras JM, Corrales RM, Calonge M. Successful Consecutive Expansion of Limbal Explants Using a Biosafe Culture Medium under Feeder Layer-Free Conditions. Curr Eye Res. 2017 May;42(5):685-695. doi: 10.1080/02713683.2016.1250278. Epub 2016 Dec 2.
PubMed 27911610Lopez-Paniagua M, Nieto-Miguel T, de la Mata A, Dziasko M, Galindo S, Rey E, Herreras JM, Corrales RM, Daniels JT, Calonge M. Comparison of functional limbal epithelial stem cell isolation methods. Exp Eye Res. 2016 May;146:83-94. doi: 10.1016/j.exer.2015.12.002. Epub 2015 Dec 17.
PubMed 26704459Ramirez BE, Sanchez A, Herreras JM, Fernandez I, Garcia-Sancho J, Nieto-Miguel T, Calonge M. Stem Cell Therapy for Corneal Epithelium Regeneration following Good Manufacturing and Clinical Procedures. Biomed Res Int. 2015;2015:408495. doi: 10.1155/2015/408495. Epub 2015 Sep 16.
PubMed 26451369Ramirez BE, Victoria DA, Murillo GM, Herreras JM, Calonge M. In vivo confocal microscopy assessment of the corneoscleral limbal stem cell niche before and after biopsy for cultivated limbal epithelial transplantation to restore corneal epithelium. Histol Histopathol. 2015 Feb;30(2):183-92. doi: 10.14670/HH-30.183. Epub 2014 Jul 30.
PubMed 25075515de la Mata A, Nieto-Miguel T, Lopez-Paniagua M, Galindo S, Aguilar MR, Garcia-Fernandez L, Gonzalo S, Vazquez B, Roman JS, Corrales RM, Calonge M. Chitosan-gelatin biopolymers as carrier substrata for limbal epithelial stem cells. J Mater Sci Mater Med. 2013 Dec;24(12):2819-29. doi: 10.1007/s10856-013-5013-3. Epub 2013 Jul 28.
PubMed 23892486Nieto-Miguel T, Galindo S, Reinoso R, Corell A, Martino M, Perez-Simon JA, Calonge M. In vitro simulation of corneal epithelium microenvironment induces a corneal epithelial-like cell phenotype from human adipose tissue mesenchymal stem cells. Curr Eye Res. 2013 Sep;38(9):933-44. doi: 10.3109/02713683.2013.802809. Epub 2013 Jun 14.
PubMed 23767776Lopez-Paniagua M, Nieto-Miguel T, de la Mata A, Galindo S, Herreras JM, Corrales RM, Calonge M. Consecutive expansion of limbal epithelial stem cells from a single limbal biopsy. Curr Eye Res. 2013 May;38(5):537-49. doi: 10.3109/02713683.2013.767350. Epub 2013 Feb 13.
PubMed 23405945Nieto-Miguel T, Calonge M, de la Mata A, Lopez-Paniagua M, Galindo S, de la Paz MF, Corrales RM. A comparison of stem cell-related gene expression in the progenitor-rich limbal epithelium and the differentiating central corneal epithelium. Mol Vis. 2011;17:2102-17. Epub 2011 Aug 10.
PubMed 21850186de la Mata A, Mateos-Timoneda MA, Nieto-Miguel T, Galindo S, Lopez-Paniagua M, Planell JA, Engel E, Calonge M. Poly-l/dl-lactic acid films functionalized with collagen IV as carrier substrata for corneal epithelial stem cells. Colloids Surf B Biointerfaces. 2019 May 1;177:121-129. doi: 10.1016/j.colsurfb.2019.01.054. Epub 2019 Jan 28.
PubMed 30716697
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cultivated Limbal Epithelial Transplantation (CLET) for Limbal Stem Cell Deficiency (LSCD): an Observational Study on Safety and Effectiveness
- ClinicalTrials.gov ID
- NCT03884569
- Acronym / sponsor ID
- CLET-4-LSCD / IOBA201901
- Conditions
- Limbal Stem-cell Deficiency
- Keywords
- limbal stem cell deficiency, corneal failure, limbal epithelial stem cells, ocular surface, corneal blindness
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Instituto Universitario de Oftalmobiología Aplicada (Institute of Applied Ophthalmobiology) - IOBAUniversity, hospital or other
- Collaborators
- Citospin, Red de Terapia Celular, University of Valladolid
- Study start
- Nov 2025 (estimated)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 21 Mar 2019 (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.
CLET is a published treatment for the management of corneal failure due to extensive LSCD. Due to our previous studies on this novel treatment, the regulatory agency of Spain "Agencia Española de Medicamentos y Productos Sanitarios (AEMPS)" authorized our institution (IOBA-University of Valladolid) to perform this kind of therapy (CLET) in a case-by-case base following the Special Situation Medicines Policy Procedure in Spain. Upon approval of the permanent authorization patients will be included as specified by AEMPS.The objective of this study is to perform a protocolized treatment and follow up so that results can be reported to the scientific community.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients treated with CLET | – | –Previously treated with CLET patients are included retrospectively, as the follow-up procedure is already stablished in our centre, and patients treated following standard care or through "drugs-in-special-situation" request in Spain prospectively. Patients are not treated to be included in the study, only the follow-up variables are taken into account. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients diagnosed with corneal failure due to LSCD who accept and sign the informed written consent treatment to be treated with CLET
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Points of improvement in the Single Item Dry Eye Questionnaire (SIDEQ)
Time frame: 6 months
The SIDEQ gives a 0-4 score about the presence of dryness, foreign body sensation, burning/stinging, pain, itching, sensitivity to light, and blurred vision, where higher scores indicate higher intensity of the symptom (maximun score: 28). One of the primary outcomes for this work is the improvement in any of the four questionnaires shown here.
Points of improvement about the Ocular Surface Disease Index (OSDI)
Time frame: 6 months
The OSDI evaluates ocular surface symptoms with 12 questions, and scores >12 indicate abnormal symptomatology, and >32 means severe symptoms (maximum score 100). One of the primary outcomes for this work is the improvement in any of the four questionnaires shown here.
Points of improvement in the National Eye Institute 25-item Visual Function Questionnaire (NEI-VFQ25)
Time frame: 6 months
The visual function-related aspects of the quality of life were evaluated with the NEI-VFQ25, where higher scores on a 0 to 100 scale indicate better function. One of the primary outcomes for this work is the improvement in any of the four questionnaires shown here.
Points of improvement in the Change in Dry Eye Symptoms Questionnaire (CDES-Q)
Time frame: 6 months
The CDES-Q evaluates ocular surface symptoms with two questions, CDES-Q1 and CDES-Q2. CDES-Q1 evaluates the change in symptoms occured since the previous examination (same, better or worse). CDES-Q2 evaluates the magnitude of the change in a scale from 0 to 10, where 0 means "slightly better/worse" and 10 means "extremely better/worse". One of the primary outcomes for this work is the improvement in any of the four questionnaires shown here.
Percentage of improvement in corneal conjunctivalization
Time frame: 6 months
Percentage of corneal area with conjunctivalization (superficial opacity and/or superficial neovascularization) will be measured.
Complete absence of persistent epithelial defects
Time frame: 6 months
Corneal fluorescein staining has to rule out epithelial breakdown
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2025.
- Results publication: PubMed 30578758Calonge M, Perez I, Galindo S, Nieto-Miguel T, Lopez-Paniagua M, Fernandez I, Alberca M, Garcia-Sancho J, Sanchez A, Herreras JM. A proof-of-concept clinical trial using mesenchymal stem cells for the treatment of corneal epithelial stem cell deficiency. Transl Res. 2019 Apr;206:18-40. doi: 10.1016/j.trsl.2018.11.003. Epub 2018 Nov 22.
- Results publication: PubMed 28758321Galindo S, Herreras JM, Lopez-Paniagua M, Rey E, de la Mata A, Plata-Cordero M, Calonge M, Nieto-Miguel T. Therapeutic Effect of Human Adipose Tissue-Derived Mesenchymal Stem Cells in Experimental Corneal Failure Due to Limbal Stem Cell Niche Damage. Stem Cells. 2017 Oct;35(10):2160-2174. doi: 10.1002/stem.2672. Epub 2017 Aug 10.
- Results publication: PubMed 27911610Lopez-Paniagua M, Nieto-Miguel T, de la Mata A, Galindo S, Herreras JM, Corrales RM, Calonge M. Successful Consecutive Expansion of Limbal Explants Using a Biosafe Culture Medium under Feeder Layer-Free Conditions. Curr Eye Res. 2017 May;42(5):685-695. doi: 10.1080/02713683.2016.1250278. Epub 2016 Dec 2.
- Results publication: PubMed 26704459Lopez-Paniagua M, Nieto-Miguel T, de la Mata A, Dziasko M, Galindo S, Rey E, Herreras JM, Corrales RM, Daniels JT, Calonge M. Comparison of functional limbal epithelial stem cell isolation methods. Exp Eye Res. 2016 May;146:83-94. doi: 10.1016/j.exer.2015.12.002. Epub 2015 Dec 17.
- Results publication: PubMed 26451369Ramirez BE, Sanchez A, Herreras JM, Fernandez I, Garcia-Sancho J, Nieto-Miguel T, Calonge M. Stem Cell Therapy for Corneal Epithelium Regeneration following Good Manufacturing and Clinical Procedures. Biomed Res Int. 2015;2015:408495. doi: 10.1155/2015/408495. Epub 2015 Sep 16.
- Results publication: PubMed 25075515Ramirez BE, Victoria DA, Murillo GM, Herreras JM, Calonge M. In vivo confocal microscopy assessment of the corneoscleral limbal stem cell niche before and after biopsy for cultivated limbal epithelial transplantation to restore corneal epithelium. Histol Histopathol. 2015 Feb;30(2):183-92. doi: 10.14670/HH-30.183. Epub 2014 Jul 30.
- Results publication: PubMed 23892486de la Mata A, Nieto-Miguel T, Lopez-Paniagua M, Galindo S, Aguilar MR, Garcia-Fernandez L, Gonzalo S, Vazquez B, Roman JS, Corrales RM, Calonge M. Chitosan-gelatin biopolymers as carrier substrata for limbal epithelial stem cells. J Mater Sci Mater Med. 2013 Dec;24(12):2819-29. doi: 10.1007/s10856-013-5013-3. Epub 2013 Jul 28.
- Results publication: PubMed 23767776Nieto-Miguel T, Galindo S, Reinoso R, Corell A, Martino M, Perez-Simon JA, Calonge M. In vitro simulation of corneal epithelium microenvironment induces a corneal epithelial-like cell phenotype from human adipose tissue mesenchymal stem cells. Curr Eye Res. 2013 Sep;38(9):933-44. doi: 10.3109/02713683.2013.802809. Epub 2013 Jun 14.
- Results publication: PubMed 23405945Lopez-Paniagua M, Nieto-Miguel T, de la Mata A, Galindo S, Herreras JM, Corrales RM, Calonge M. Consecutive expansion of limbal epithelial stem cells from a single limbal biopsy. Curr Eye Res. 2013 May;38(5):537-49. doi: 10.3109/02713683.2013.767350. Epub 2013 Feb 13.
- Results publication: PubMed 21850186Nieto-Miguel T, Calonge M, de la Mata A, Lopez-Paniagua M, Galindo S, de la Paz MF, Corrales RM. A comparison of stem cell-related gene expression in the progenitor-rich limbal epithelium and the differentiating central corneal epithelium. Mol Vis. 2011;17:2102-17. Epub 2011 Aug 10.
- Results publication: PubMed 30716697de la Mata A, Mateos-Timoneda MA, Nieto-Miguel T, Galindo S, Lopez-Paniagua M, Planell JA, Engel E, Calonge M. Poly-l/dl-lactic acid films functionalized with collagen IV as carrier substrata for corneal epithelial stem cells. Colloids Surf B Biointerfaces. 2019 May 1;177:121-129. doi: 10.1016/j.colsurfb.2019.01.054. Epub 2019 Jan 28.
- 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Limbal Stem-cell Deficiency, run by Instituto Universitario de Oftalmobiología Aplicada (Institute of Applied Ophthalmobiology) - IOBA at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 16 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Margarita Calonge, MD, PhD (34983184750, calonge@ioba.med.uva.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Points of improvement in the Single Item Dry Eye Questionnaire (SIDEQ) (time frame: 6 months). The study lists 6 primary outcomes in all. 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 NCT03884569, which also lists 11 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 16 May 2025.