Back to resultsSafety and Efficacy of Pluripotent Stem Cell-derived Mesenchymal Stem Cell Exosome (PSC-MSC-Exo) Eye Drops Treatment for Dry Eye Diseases Post Refractive Surgery and Associated With Blepharospasm
Primary Purpose
Dry Eye Disease
Status
Not yet recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Pluripotent Stem Cell-derived Mesenchymal Stem Cell Exosome (PSC-MSC-Exo) Eye Drops
Sponsored by
About this trial
This is an interventional treatment trial for Dry Eye Disease focused on measuring dry eye disease; post refractive surgery; blepharospasm; exosomes; mesenchymal stem cell; pluripotent stem cell
Eligibility Criteria
Inclusion Criteria: clinical diagnosis of apparent dry eye symptoms by ophthalmologists. patients experience dry eye symptoms with a definitive history of FS-LASIK or SMILE surgery, or blepharospasm, and previous application of artificial tears for more than 3 months could not relieve the dry eye symptoms. have the following symptoms in at least one eye: dryness, burning sensation, foreign body sensation, discomfort in the ocular surface or visual fatigue; tear secretion test (Schirmer's Test) of either eye ≤ 10 mm / 5 min; the corneal fluorescein staining score (FLCs) was more than 3 and less than 6. Tear break up time (TBUT) is less than 10 seconds. Exclusion Criteria: Those who are allergic to any component of the drug in this study; Pregnant or nursing women; Patients with active fungal, bacterial or viral keratitis or conjunctivitis; have serious heart, lung, liver or kidney diseases; Other incurable ocular diseases before the study; such as glaucoma, uveitis, retinitis pigmentosa. Wearing contact lenses and unwilling to take off in the study; Performed ocular surgery (including cataract surgery) in recent three months; Enrolled in other interventional clinical studies at the same time; Application of eye drops that might affect the clinical study in the past 24 hours; Unable to complete the study according to the investigators' requirements; Application of eye drops other than artificial tears. Application of systemic medication known to reduce tear production, such as anti-anxiety drugs, antipsychotics and steroids. Eyelids or eyelashes anomaly. Serious systemic diseases. Refused to sign the informed consent form to participate in the experiment.
Sites / Locations
- 2nd Affiliated Hospital, School of Medicine, Zhejiang University
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
PSC-MSC-Exo Eye Drops Treatment
Arm Description
Participants will receive artificial tears for 2 weeks to get the normalized baseline, followed by PSC-MSC-Exo eye drop intervention for 12 weeks.
Outcomes
Primary Outcome Measures
Change in Ocular Surface Disease Index (OSDI)
The OSDI questionnaire contains 12 questions to measure dry eye symptoms. OSDI scores range from 0 to 100. The lower the score, the more alleviation of dry eye symptoms. Compared with the baseline, a reduction of more than 10 points indicates improvement.
Secondary Outcome Measures
Tear Secretion Test (Schirmer test)
A paper strip is placed 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. A positive change from baseline indicates an improvement in each eye.
Tear Film Break-up Time
Time required for dry spots to appear on the surface of the eye after blinking was measured in seconds. A positive change from baseline indicates improvement in each eye.
Ocular Surface Staining Score
Damage of the ocular surface was measured by slit-lamp examination after staining with non-toxic fluorescein sodium. 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. A negative change from baseline indicates an improvement in each eye.
Best Corrected Visual Acuity (BCVA)
Whether exosomes affect visual acuity.
Conjunctiva Redness Score
Conjunctival hyperemia was graded in each eye 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. A negative change from baseline indicates an improvement in each eye.
Tear Meniscus Height
The distance between the line of reflection along the top of the tear prism to the edge of the eyelid was measured in millimeters. A positive number change from baseline indicates improvement.
Corneal confocal microscopy
The morphology, distribution and quantity of corneal nerve fibers were recorded by confocal image after LASIK and SMILE.
Meibomian gland expressibility scores
Squeeze the central meibomian glands of the lower eyelid and assess the expressibility of the five central glands, where 0= All glands have meibum extruded, 1= 3-4 glands have meibum extruded, 2=1-2 glands have meibum extruded, 3=no glands have meibum extruded.
Meibomian Glands Photography
The morphology, quantity and blockage of meibomian gland can be assigned a score of 0 to 3 points according to meibomian gland dropout, where 0=normal without dropout; 1=meibomian gland dropout<1/3; 2=meibomian gland dropout 1/3-2/3; 3=meibomian gland dropout >2/3. The total score of upper and lower meibomian glands is 6 points, of which Grade 0=0-1 point; Grade 1=2-3 points; Grade 2=4-5 points; Grade 3=6 points.
Full Information
NCT ID
NCT05738629
First Posted
February 13, 2023
Last Updated
February 21, 2023
Sponsor
Second Affiliated Hospital, School of Medicine, Zhejiang University
Collaborators
Zhejiang University, Hangzhou yuansheng biotechnology Co., Ltd
1. Study Identification
Unique Protocol Identification Number
NCT05738629
Brief Title
Safety and Efficacy of Pluripotent Stem Cell-derived Mesenchymal Stem Cell Exosome (PSC-MSC-Exo) Eye Drops Treatment for Dry Eye Diseases Post Refractive Surgery and Associated With Blepharospasm
Official Title
A Clinical Study of the Safety and Efficacy of Pluripotent Stem Cell-derived Mesenchymal Stem Cell Exosome (PSC-MSC-Exo) Eye Drops Treatment for Dry Eye Diseases Post Refractive Surgery and Associated With Blepharospasm
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
March 2023 (Anticipated)
Primary Completion Date
February 2025 (Anticipated)
Study Completion Date
February 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Second Affiliated Hospital, School of Medicine, Zhejiang University
Collaborators
Zhejiang University, Hangzhou yuansheng biotechnology Co., Ltd
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the preliminary safety and effectiveness of Pluripotent Stem Cell-derived Mesenchymal Stem Cell Exosome (PSC-MSC-Exo) Eye Drops in the treatment of dry eye diseases post refractive surgery and associated with blepharospasm
Detailed Description
Dry eye disease (DED) is a multifactorial disease of the ocular surface characterized by instability of the tear film and the prevalence has been estimated to reach 20%-40%. Especially, dry eye symptoms are common complaints of patients with blepharospasm or refractive surgery history, seriously affecting their quality of life. There are many conventional therapies for DED which include ocular lubricants, oral essential fatty acid supplementation, lid hygiene and warm compresses, punctal occlusion, various treatments to obstructed meibomian glands, topical antibiotics, topical corticosteroids, topical secretagogues, topical non-glucocorticoid immunomodulatory drugs and scleral contact lenses. However, the overall efficacy is still unsatisfactory with apparent side effects, long periods of treatment, and high-costs. Mesenchymal stem cell-derived exosomes (MSC-Exo) are 30-150nm microvesicles secreted by mesenchymal stem cells (MSCs), which can mediate the therapeutic efficacy of mesenchymal stem cells by the encapsulated proteins, miRNAs and other bioactive substances, and showed potential in the treatment of various diseases. This study aims to evaluate the preliminary safety and effectiveness of PSC-MSC-Exo in the treatment of dry eye diseases post refractive surgery and associated with blepharospasm.
This is an open-label, single-arm, before-after study with 12 subjects with dry eye diseases and the history of refractive surgery or blepharospasm. There are 5 visits over the course of 12 weeks. Visit 1: Week-1 Visit 2: Week-2 Visit 3: Week-4 Visit 4: Week-8 Visit 5: Week-12
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dry Eye Disease
Keywords
dry eye disease; post refractive surgery; blepharospasm; exosomes; mesenchymal stem cell; pluripotent stem cell
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
PSC-MSC-Exo Eye Drops Treatment
Arm Type
Experimental
Arm Description
Participants will receive artificial tears for 2 weeks to get the normalized baseline, followed by PSC-MSC-Exo eye drop intervention for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Pluripotent Stem Cell-derived Mesenchymal Stem Cell Exosome (PSC-MSC-Exo) Eye Drops
Intervention Description
Participants will receive artificial tears for 2 weeks to get the normalized baseline, followed by PSC-MSC-Exo eye drops 0.125 ml/single eye/one time, four times a day for 12 weeks. The follow-up visit will be 12 weeks since the administration of PSC-MSC-Exo eye drops.
Primary Outcome Measure Information:
Title
Change in Ocular Surface Disease Index (OSDI)
Description
The OSDI questionnaire contains 12 questions to measure dry eye symptoms. OSDI scores range from 0 to 100. The lower the score, the more alleviation of dry eye symptoms. Compared with the baseline, a reduction of more than 10 points indicates improvement.
Time Frame
1 weeks, 2 weeks, 4 weeks, 8 weeks,12 weeks
Secondary Outcome Measure Information:
Title
Tear Secretion Test (Schirmer test)
Description
A paper strip is placed 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. A positive change from baseline indicates an improvement in each eye.
Time Frame
1 weeks, 2 weeks, 4 weeks, 8 weeks,12 weeks
Title
Tear Film Break-up Time
Description
Time required for dry spots to appear on the surface of the eye after blinking was measured in seconds. A positive change from baseline indicates improvement in each eye.
Time Frame
1 weeks, 2 weeks, 4 weeks, 8 weeks,12 weeks
Title
Ocular Surface Staining Score
Description
Damage of the ocular surface was measured by slit-lamp examination after staining with non-toxic fluorescein sodium. 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. A negative change from baseline indicates an improvement in each eye.
Time Frame
1 weeks, 2 weeks, 4 weeks, 8 weeks,12 weeks
Title
Best Corrected Visual Acuity (BCVA)
Description
Whether exosomes affect visual acuity.
Time Frame
1 weeks, 2 weeks, 4 weeks, 8 weeks,12 weeks
Title
Conjunctiva Redness Score
Description
Conjunctival hyperemia was graded in each eye 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. A negative change from baseline indicates an improvement in each eye.
Time Frame
1 weeks, 2 weeks, 4 weeks, 8 weeks,12 weeks
Title
Tear Meniscus Height
Description
The distance between the line of reflection along the top of the tear prism to the edge of the eyelid was measured in millimeters. A positive number change from baseline indicates improvement.
Time Frame
1 weeks, 2 weeks, 4 weeks, 8 weeks,12 weeks
Title
Corneal confocal microscopy
Description
The morphology, distribution and quantity of corneal nerve fibers were recorded by confocal image after LASIK and SMILE.
Time Frame
1 weeks, 2 weeks, 4 weeks, 8 weeks,12 weeks
Title
Meibomian gland expressibility scores
Description
Squeeze the central meibomian glands of the lower eyelid and assess the expressibility of the five central glands, where 0= All glands have meibum extruded, 1= 3-4 glands have meibum extruded, 2=1-2 glands have meibum extruded, 3=no glands have meibum extruded.
Time Frame
1 weeks, 2 weeks, 4 weeks, 8 weeks,12 weeks
Title
Meibomian Glands Photography
Description
The morphology, quantity and blockage of meibomian gland can be assigned a score of 0 to 3 points according to meibomian gland dropout, where 0=normal without dropout; 1=meibomian gland dropout<1/3; 2=meibomian gland dropout 1/3-2/3; 3=meibomian gland dropout >2/3. The total score of upper and lower meibomian glands is 6 points, of which Grade 0=0-1 point; Grade 1=2-3 points; Grade 2=4-5 points; Grade 3=6 points.
Time Frame
1 weeks, 2 weeks, 4 weeks, 8 weeks,12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
clinical diagnosis of apparent dry eye symptoms by ophthalmologists.
patients experience dry eye symptoms with a definitive history of FS-LASIK or SMILE surgery, or blepharospasm, and previous application of artificial tears for more than 3 months could not relieve the dry eye symptoms.
have the following symptoms in at least one eye: dryness, burning sensation, foreign body sensation, discomfort in the ocular surface or visual fatigue;
tear secretion test (Schirmer's Test) of either eye ≤ 10 mm / 5 min;
the corneal fluorescein staining score (FLCs) was more than 3 and less than 6.
Tear break up time (TBUT) is less than 10 seconds.
Exclusion Criteria:
Those who are allergic to any component of the drug in this study;
Pregnant or nursing women;
Patients with active fungal, bacterial or viral keratitis or conjunctivitis;
have serious heart, lung, liver or kidney diseases;
Other incurable ocular diseases before the study; such as glaucoma, uveitis, retinitis pigmentosa.
Wearing contact lenses and unwilling to take off in the study;
Performed ocular surgery (including cataract surgery) in recent three months;
Enrolled in other interventional clinical studies at the same time;
Application of eye drops that might affect the clinical study in the past 24 hours;
Unable to complete the study according to the investigators' requirements;
Application of eye drops other than artificial tears.
Application of systemic medication known to reduce tear production, such as anti-anxiety drugs, antipsychotics and steroids.
Eyelids or eyelashes anomaly.
Serious systemic diseases.
Refused to sign the informed consent form to participate in the experiment.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Qi Gao, Doc.
Phone
86-15088774002
Email
gaoqi8977@zju.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Juan Ye, Doc.
Organizational Affiliation
2nd Affiliated Hospital, School of Medicine, Zhejiang University
Official's Role
Study Chair
Facility Information:
Facility Name
2nd Affiliated Hospital, School of Medicine, Zhejiang University
City
Hanzhou
State/Province
Zhejiang
ZIP/Postal Code
310000
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Qi Gao, Doc
Phone
86-15088774002
12. IPD Sharing Statement
Learn more about this trial
Safety and Efficacy of Pluripotent Stem Cell-derived Mesenchymal Stem Cell Exosome (PSC-MSC-Exo) Eye Drops Treatment for Dry Eye Diseases Post Refractive Surgery and Associated With Blepharospasm
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