Effect of UMSCs Derived Exosomes on Dry Eye in Patients With cGVHD

NCT ID: NCT04213248

Last Updated: 2022-02-11

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-21
• Study Completion Date: 2023-12-31

Brief 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).

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

UMSC-exo treatment

Participants will receive artificial tears for 2 weeks to get the normalized baseline, followed by UMSC-exo intervention for 2 weeks.

Group Type: EXPERIMENTAL

Umbilical Mesenchymal Stem Cells derived Exosomes

Intervention Type: DRUG

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.

Interventions

Umbilical Mesenchymal Stem Cells derived Exosomes

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.

Intervention Type: DRUG

Other Intervention Names

UMSC-exo

Eligibility Criteria

Inclusion Criteria

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:

1. have the following symptoms in at least one eye: dryness, burning sensation, foreign body sensation, discomfort in the ocular surface or visual fatigue;

2. tear secretion test (Schirmer's Test) of either eye ≤ 10 mm / 5 min;

3. the corneal fluorescein staining score (CFS) was more than 4;

4. Tear break time (TBUT) is less than 10 seconds.

Exclusion Criteria

1. Those who are allergic to any component of the drug in this study;

2. Pregnant or nursing women;

3. Patients with active fungal, bacterial or viral keratitis or conjunctivitis;

4. have serious heart, lung, liver or kidney diseases;

5. Other incurable ocular diseases before the study; such as glaucoma, uveitis, retinitis pigmentosa.

6. Wearing contact lenses and unwilling to take off in the study;

7. Performed ocular surgery (including cataract surgery) in recent three months;

8. Enrolled in other interventional clinical studies at the same time;

9. Application of eye drops that might affect the clinical study in the past 24 hours;

10. Unable to complete the study according to the investigators' requirements;

11. Serious systemic diseases.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Zhongshan Ophthalmic Center, Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Xialin Liu, Prof.

Role: PRINCIPAL_INVESTIGATOR

Zhongshan Ophthalmic Center, Sun Yat-sen University

Locations

Zhongshan Ophthalmic Center

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Tian Zhou

Role: CONTACT

zhoutian@gzzoc.com

(020)66615460

Facility Contacts

Tian Zhou, phD

Role: primary

zhoutian@gzzoc.com

References

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.

Reference Type: DERIVED

PMID: 39839752 (View on PubMed)

Other Identifiers

2019KYPJ048

Identifier Type: -

Identifier Source: org_study_id