Clinical trial NCT04213248: Effect of UMSCs Derived Exosomes on Dry Eye in Patients With cGVHD
Official title: Effect of Umbilical Mesenchymal Stem Cells Derived Exosomes on Dry Eye in Patients With Chronic Graft Versus Host Diseases
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Dry Eye
Keywords: Dry eye
UMSC
Exosome
cGVHD
Lead sponsor: Zhongshan Ophthalmic Center, Sun Yat-sen University
Sponsor class: OTHER
First posted: 2019-12-30
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Changes in Ocular Surface Disease Index (OSDI) Score
timeFrame: 3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks
Secondary outcomes:
measure: Changes in tear secretion amount by Schirmer's Test
timeFrame: 3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks
measure: Changes in Tear break time
timeFrame: 3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks
measure: Changes in Ocular Surface Staining
timeFrame: 3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks
measure: Changes in best corrected visual acuity (BCVA).
timeFrame: 3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks
measure: Changes in conjunctiva redness score
timeFrame: 3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks
measure: Changes in tear meniscus height
timeFrame: 3 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 12 weeks
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Zhongshan Ophthalmic Center
state: Guangdong
Study officials:
affiliation: Zhongshan Ophthalmic Center, Sun Yat-sen University
name: Xialin Liu, Prof.
role: PRINCIPAL_INVESTIGATOR
References: