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

Dry Eye Clinical Trial

Official title:

Effect of Umbilical Mesenchymal Stem Cells Derived Exosomes on Dry Eye in Patients With Chronic Graft Versus Host Diseases

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04213248
• Other study ID #: 2019KYPJ048
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 21, 2020
• Est. completion date: December 2023

Study information

• Verified date: February 2022
• Source: Zhongshan Ophthalmic Center, Sun Yat-sen University
• Contact: Tian Zhou
• Phone: (020)66615460
• Email: zhoutian[@]gzzoc.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 27
• Est. completion date: December 2023
• Est. primary completion date: May 18, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Dry Eye
• Dry Eye Syndromes
• Keratoconjunctivitis Sicca

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
China	Zhongshan Ophthalmic Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Zhongshan Ophthalmic Center, Sun Yat-sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks
Secondary	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.	3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks
Secondary	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	3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks
Secondary	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	3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks
Secondary	Changes in best corrected visual acuity (BCVA).	to understand the effect of exosomes on visual acuity	3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks
Secondary	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.	3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks
Secondary	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.	3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks