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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04213248
Recruitment Status : Recruiting
First Posted : December 30, 2019
Last Update Posted : February 21, 2020
Sponsor:
Information provided by (Responsible Party):
Zhongshan Ophthalmic Center, Sun Yat-sen University

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).

Condition or disease Intervention/treatment Phase
Dry Eye Drug: Umbilical Mesenchymal Stem Cells derived Exosomes Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 27 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effect of Umbilical Mesenchymal Stem Cells Derived Exosomes on Dry Eye in Patients With Chronic Graft Versus Host Diseases
Actual Study Start Date : February 18, 2020
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : May 2020


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 Name: UMSC-exo




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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. 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


  4. 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

  5. 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.

  6. 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.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 (FLCs) was less than 6;
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04213248


Contacts
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Contact: Tian Zhou (020)66615460 zhoutian@gzzoc.com

Locations
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China, Guangdong
Zhongshan Ophthalmic Center Recruiting
Guangzhou, Guangdong, China, 510000
Contact: Tian Zhou, phD       zhoutian@gzzoc.com   
Sponsors and Collaborators
Zhongshan Ophthalmic Center, Sun Yat-sen University
Investigators
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Principal Investigator: Xialin Liu, Prof. Zhongshan Ophthalmic Center, Sun Yat-sen University
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Responsible Party: Zhongshan Ophthalmic Center, Sun Yat-sen University
ClinicalTrials.gov Identifier: NCT04213248    
Other Study ID Numbers: 2019KYPJ048
First Posted: December 30, 2019    Key Record Dates
Last Update Posted: February 21, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Zhongshan Ophthalmic Center, Sun Yat-sen University:
Dry eye
UMSC
Exosome
cGVHD
Additional relevant MeSH terms:
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Keratoconjunctivitis Sicca
Dry Eye Syndromes
Keratoconjunctivitis
Conjunctivitis
Conjunctival Diseases
Eye Diseases
Keratitis
Corneal Diseases
Lacrimal Apparatus Diseases