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

February 10, 2022 updated by: Zhongshan Ophthalmic Center, Sun Yat-sen University

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

27

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510000
        • Recruiting
        • Zhongshan Ophthalmic Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 66 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: UMSC-exo treatment
Participants will receive artificial tears for 2 weeks to get the normalized baseline, followed by UMSC-exo intervention for 2 weeks.
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.
Other Names:
  • UMSC-exo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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
Changes in Tear break time
Time Frame: 3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks
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
Changes in Ocular Surface Staining
Time Frame: 3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks

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
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
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
Changes in conjunctiva redness score
Time Frame: 3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks
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
Changes in tear meniscus height
Time Frame: 3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Zhongshan Ophthalmic Center, Sun Yat-sen University

Investigators

  • Principal Investigator: Xialin Liu, Prof., Zhongshan Ophthalmic Center, Sun Yat-sen University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 21, 2020

Primary Completion (Anticipated)

May 18, 2023

Study Completion (Anticipated)

December 1, 2023

Study Registration Dates

First Submitted

December 25, 2019

First Submitted That Met QC Criteria

December 25, 2019

First Posted (Actual)

December 30, 2019

Study Record Updates

Last Update Posted (Actual)

February 11, 2022

Last Update Submitted That Met QC Criteria

February 10, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2019KYPJ048

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Dry Eye

Clinical Trials on Umbilical Mesenchymal Stem Cells derived Exosomes

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Belarus

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe