Dry EyePhase 1/2NCT04213248
Effect of UMSCs Derived Exosomes on Dry Eye in Patients With cGVHD
A Phase 1/2 study testing Umbilical Mesenchymal Stem Cells derived Exosomes in people with Dry Eye, run by Zhongshan Ophthalmic Center, Sun Yat-sen University at 1 site in China.
Trial summary
The purpose of this study is to determine whether Umbilical Mesenchymal Stem Cells (UMSCs) derived Exosomes could alleviate dry eye symptoms in patients with chronic Graft Versus Host Diseases (cGVHD). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Dry Eye
- What is being tested?
- Umbilical Mesenchymal Stem Cells derived Exosomes
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteChina
- Study dates
- 21 Feb 2020to Dec 2023
- Phase
- Phase 1/2
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosed cGVHD with apparent dry eye symptoms by intern specialists and ophthalmologists, and previous application of artificial tears could not relieve the dry eye symptoms.
- And meet the following standards:
- have the following symptoms in at least one eye: dryness, burning sensation, foreign body sensation, discomfort in the ocular surface or visual fatigue;
- tear secretion test (Schirmer's Test) of either eye ≤ 10 mm / 5 min;
- the corneal fluorescein staining score (CFS) was more than 4;
- Tear break time (TBUT) is less than 10 seconds.
Who cannot join
- Those who are allergic to any component of the drug in this study;
- Pregnant or nursing women;
- Patients with active fungal, bacterial or viral keratitis or conjunctivitis;
- have serious heart, lung, liver or kidney diseases;
- Other incurable ocular diseases before the study; such as glaucoma, uveitis, retinitis pigmentosa.
- Wearing contact lenses and unwilling to take off in the study;
Show all 11Show fewer
- Performed ocular surgery (including cataract surgery) in recent three months;
- Enrolled in other interventional clinical studies at the same time;
- Application of eye drops that might affect the clinical study in the past 24 hours;
- Unable to complete the study according to the investigators' requirements;
- Serious systemic diseases.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Zhongshan Ophthalmic Center
Guangzhou, Guangdong, 510000
Tian Zhou, phD, zhoutian@gzzoc.com
About this study
Official title: Effect of Umbilical Mesenchymal Stem Cells Derived Exosomes on Dry Eye in Patients With Chronic Graft Versus Host Diseases
The purpose of this study is to determine whether Umbilical Mesenchymal Stem Cells (UMSCs) derived Exosomes could alleviate dry eye symptoms in patients with chronic Graft Versus Host Diseases (cGVHD).
Read the detailed description
Among patients with cGVHD, 60% - 90% are affected by dry eye symptoms, presenting as progressive development of dryness, foreign body sensation, photophobia, pain and even blindness, which seriously affect their life quality. At present, the standard first-line treatment of cGVHD is still hormone or combined with immunosuppressant of cyclosporine. The dry eyes related to cGVHD are treated with artificial tears, lacrimal punctum embolization, local immunosuppressant or even blepharoplasty to reduce dry eye symptoms. Although a variety of new immunosuppressants and monoclonal antibodies have been used in clinic, the overall efficacy is still unsatisfactory with apparent side effects, and the period of treatment is long with high-costs. Therefore, it is an urgent task for clinicians to explore new methods of cGVHD related dry eye therapy and improve the survival rate and quality of life of patients.
Exosomes are a kind of membrane vesicles secreted by parental cells, which can mediate the transfer of RNA, protein, DNA and other functional molecules between cells and regulate the function of target cells. The therapeutic potential of UMSC exosomes has been widely studied in diseases of liver, kidney, skin and so on. Previously, we found that UMSC exosomes can significantly alleviate the symptoms of dry eye in the dry eye animal model. At present, we plan to clarify its efficacy in clinical research.
The main objective of this study is to assess the alleviation of dry eye symptoms in patients with cGVHD after UMSC-exo treatment by measuring Ocular Surface Index Score (OSDI), and the second objective include the measurement of tear secretion amount, tear break time, the areas stained by fluorescent, ocular redness, tear meniscus and best corrected visual acuity.
Approximately 27 study subjects will be recruited. The treatment group will receive artificial tears for 2 weeks to normalize the baseline, followed by intervention of UMSC-exo 10ug/drop, four times a day for 14 days. The follow-up visit will be 12-week, progression of dry eye will be measured.
- Conditions
- Dry Eye
- Being tested
- Umbilical Mesenchymal Stem Cells derived Exosomes
- Keywords
- Dry eye, UMSC, Exosome, cGVHD
- Medical subject headings
- Dry Eye Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Umbilical Mesenchymal Stem Cells derived ExosomesDrug
Also called UMSC-exo
Participants will receive artificial tears for 2 weeks to get the normalized baseline, followed by UMSC-exo 10ug/drop, four times a day for 14 days. The follow-up visit will be 12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| UMSC-exo treatment | Experimental | Participants will receive artificial tears for 2 weeks to get the normalized baseline, followed by UMSC-exo intervention for 2 weeks. Receives: Drug: Umbilical Mesenchymal Stem Cells derived Exosomes |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Ocular Surface Disease Index (OSDI) Score
The OSDI is a 12-question validated questionnaire used to measure dry eye symptoms. The OSDI scoring scale ranges from 0 to 100. The lower the score, the more symptomatic relief from dry eye symptoms a patient experiences. Baseline-adjusted scores were tabulated; a decrease over 10 scores from baseline indicates an improvement.
Measured: 3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks
Secondary outcomes (6)
Changes in tear secretion amount by Schirmer's Test
The investigator placed a paper strip on the eye under the lower lid for a specified time period. The length of the strip wetted by the tears was measured in millimeters. Baseline-adjusted values were tabulated; a positive number change from baseline indicates an improvement in each eye individually.
Measured: 3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks
Changes in Tear break time
time required for dry spots to appear on the surface of the eye after blinking was measured in seconds. Baseline-adjusted scores were tabulated; a positive number change from baseline indicates improvement in each eye individually
Measured: 3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks
Changes in Ocular Surface Staining
Damage to the ocular surface was assessed using non-toxic ophthalmic dye during slit-lamp review. Corneal and conjunctival staining were graded as per the National Eye Institute (NEI) pictorial scale. The lower the score, the less signs of dry eye disease a patient exhibits. Baseline-adjusted scores were tabulated; a negative number change from baseline indicates an improvement in each eye individually
Damage to the ocular surface was assessed using non-toxic ophthalmic dye during slit-lamp review. Corneal and conjunctival staining were graded as per the National Eye Institute (NEI) pictorial scale. The lower the score, the less signs of dry eye disease a patient exhibits. Baseline-adjusted scores were tabulated; a negative number change from baseline indicates an improvement in each eye individually
Measured: 3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks
Changes in best corrected visual acuity (BCVA).
to understand the effect of exosomes on visual acuity
Measured: 3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks
Changes in conjunctiva redness score
Description: to explore the effect of exosomes on conjunctiva. Nasal and temporal bulbar conjunctival hyperemia were graded separately in each eye by the investigator under slit-lamp magnification by assigning a score of 0 to 4 for each quadrant based on comparison to the Allergan Dry Eye Redness Scale with photographic reference where: 0=Normal, vessels of bulbar conjunctiva are easily observed; 1=Trace redness; 2=Mild redness; 3=Moderate redness; 4=Severe redness, and each score is associated with a reference photo.
Measured: 3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks
Changes in tear meniscus height
Description: to reflect the effect of exosomes on tear production. the distance between the line of reflection along the top of the tear prism to the edge of the eyelid was measured in millimeters. Baseline-adjusted scores were tabulated; a positive number change from baseline indicates improvement. Each eye was assessed individually. Both eyes contributed to the mean.
Measured: 3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2019
- Study start21 Feb 2020
- Primary completion18 May 2023 (estimated)
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Dry EyeStudies of the same condition, open and under way.
- More trials run by Zhongshan Ophthalmic Center, Sun Yat-sen UniversityThe sponsor's other registered studies.
- 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
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Xialin Liu, Prof., Principal investigator, Zhongshan Ophthalmic Center, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04213248
- Sponsor's protocol ID
- 2019KYPJ048
- Status last verified
- Feb 2022
- First submitted
- 25 Dec 2019
- Last updated
- 11 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Randall Harrell C, Djonov V, Volarevic A, Arsenijevic A, Volarevic V. Mesenchymal Stem Cell-Sourced Exosomes as Potentially Novel Remedies for Severe Dry Eye Disease. J Ophthalmol. 2025 Jan 10;2025:5552374. doi: 10.1155/joph/5552374. eCollection 2025.
PubMed 39839752
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Umbilical Mesenchymal Stem Cells Derived Exosomes on Dry Eye in Patients With Chronic Graft Versus Host Diseases
- ClinicalTrials.gov ID
- NCT04213248
- Acronym / sponsor ID
- 2019KYPJ048
- Conditions
- Dry Eye
- Keywords
- Dry eye, UMSC, Exosome, cGVHD
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 27 participants (estimated)
- Lead sponsor
- Zhongshan Ophthalmic Center, Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 21 Feb 2020 (actual)
- Primary completion
- 18 May 2023 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 30 Dec 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.
The purpose of this study is to determine whether Umbilical Mesenchymal Stem Cells (UMSCs) derived Exosomes could alleviate dry eye symptoms in patients with chronic Graft Versus Host Diseases (cGVHD).
Detailed description
Among patients with cGVHD, 60% - 90% are affected by dry eye symptoms, presenting as progressive development of dryness, foreign body sensation, photophobia, pain and even blindness, which seriously affect their life quality. At present, the standard first-line treatment of cGVHD is still hormone or combined with immunosuppressant of cyclosporine. The dry eyes related to cGVHD are treated with artificial tears, lacrimal punctum embolization, local immunosuppressant or even blepharoplasty to reduce dry eye symptoms. Although a variety of new immunosuppressants and monoclonal antibodies have been used in clinic, the overall efficacy is still unsatisfactory with apparent side effects, and the period of treatment is long with high-costs. Therefore, it is an urgent task for clinicians to explore new methods of cGVHD related dry eye therapy and improve the survival rate and quality of life of patients.
Exosomes are a kind of membrane vesicles secreted by parental cells, which can mediate the transfer of RNA, protein, DNA and other functional molecules between cells and regulate the function of target cells. The therapeutic potential of UMSC exosomes has been widely studied in diseases of liver, kidney, skin and so on. Previously, we found that UMSC exosomes can significantly alleviate the symptoms of dry eye in the dry eye animal model. At present, we plan to clarify its efficacy in clinical research.
The main objective of this study is to assess the alleviation of dry eye symptoms in patients with cGVHD after UMSC-exo treatment by measuring Ocular Surface Index Score (OSDI), and the second objective include the measurement of tear secretion amount, tear break time, the areas stained by fluorescent, ocular redness, tear meniscus and best corrected visual acuity.
Approximately 27 study subjects will be recruited. The treatment group will receive artificial tears for 2 weeks to normalize the baseline, followed by intervention of UMSC-exo 10ug/drop, four times a day for 14 days. The follow-up visit will be 12-week, progression of dry eye will be measured.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| UMSC-exo treatment | Experimental | Drug: Umbilical Mesenchymal Stem Cells derived ExosomesParticipants will receive artificial tears for 2 weeks to get the normalized baseline, followed by UMSC-exo intervention for 2 weeks. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Diagnosed cGVHD with apparent dry eye symptoms by intern specialists and ophthalmologists, and previous application of artificial tears could not relieve the dry eye symptoms.
- have the following symptoms in at least one eye: dryness, burning sensation, foreign body sensation, discomfort in the ocular surface or visual fatigue;
- tear secretion test (Schirmer's Test) of either eye ≤ 10 mm / 5 min;
- the corneal fluorescein staining score (CFS) was more than 4;
- Tear break time (TBUT) is less than 10 seconds.
Key exclusion criteria (11 listed)
- Those who are allergic to any component of the drug in this study;
- Pregnant or nursing women;
- Patients with active fungal, bacterial or viral keratitis or conjunctivitis;
- have serious heart, lung, liver or kidney diseases;
- Other incurable ocular diseases before the study; such as glaucoma, uveitis, retinitis pigmentosa.
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 |
|---|---|---|
| Umbilical Mesenchymal Stem Cells derived ExosomesAlso: UMSC-exoParticipants will receive artificial tears for 2 weeks to get the normalized baseline, followed by UMSC-exo 10ug/drop, four times a day for 14 days. The follow-up visit will be 12 weeks. | Drug | UMSC-exo treatment |
Primary outcome
Changes in Ocular Surface Disease Index (OSDI) Score
Time frame: 3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks
The OSDI is a 12-question validated questionnaire used to measure dry eye symptoms. The OSDI scoring scale ranges from 0 to 100. The lower the score, the more symptomatic relief from dry eye symptoms a patient experiences. Baseline-adjusted scores were tabulated; a decrease over 10 scores from baseline indicates an improvement.
6 secondary outcomes
Changes in tear secretion amount by Schirmer's Test
Time frame: 3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks
Changes in Tear break time
Time frame: 3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks
Changes in Ocular Surface Staining
Time frame: 3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks
Changes in best corrected visual acuity (BCVA).
Time frame: 3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks
Changes in conjunctiva redness score
Time frame: 3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks
Changes in tear meniscus height
Time frame: 3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2022.
- Derived from this study: PubMed 39839752Randall Harrell C, Djonov V, Volarevic A, Arsenijevic A, Volarevic V. Mesenchymal Stem Cell-Sourced Exosomes as Potentially Novel Remedies for Severe Dry Eye Disease. J Ophthalmol. 2025 Jan 10;2025:5552374. doi: 10.1155/joph/5552374. eCollection 2025.
- Individual participant dataSharing planned: No
Related trials for Dry Eye
Not yet recruitingPhase 1
R-2487 in Patients With Sjogren's Syndrome (SjD)
Sjogren's Syndrome, Sjögren
RecruitingPhase 1
A Trial in Healthy Adult Participants and Adults With Autoimmune Diseases to Test How HBM7020 is Tolerated and How it Behaves in the Body
Rheumatoid Arthritis, Systemic Lupus Erythematosus
RecruitingObservational study
Pain Phenotyping of Rheumatic Diseases - An Observational Study
Rheumatic Diseases, Lupus Erythematosus, Systemic
RecruitingPhase 1/2
Autologous Transplantation of Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium for Geographic Atrophy Associated With Age-Related Macular Degeneration
Dry Age-Related Macular Degeneration, Geographic Atrophy
RecruitingObservational study
The Pathogenesis and Natural History of Sjogren's Disease
Sjogren's Syndrome, Salivary Gland
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.
Xialin Liu, Prof. principal investigator
Zhongshan Ophthalmic Center, Sun Yat-sen University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Umbilical Mesenchymal Stem Cells derived Exosomes in people with Dry Eye, run by Zhongshan Ophthalmic Center, Sun Yat-sen University at 1 site in China.
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 6 inclusion and 11 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 11 Feb 2022. 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 China. 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.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Tian Zhou ((020)66615460, zhoutian@gzzoc.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in Ocular Surface Disease Index (OSDI) Score (time frame: 3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks). 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 NCT04213248, which also lists 1 linked publication.
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 11 Feb 2022.