- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05784519
Therapeutic Effect of Stem Cell Eye Drops on Dry Eye Disease
Clinical Study of Mesenchymal Stem Cell Eye Drops for Treating Dry Eye Disease
The goal of this non-randomized, prospective, open, one-arm clinical study is to learn about the clinical efficacy of stem cell eye drops in patients with dry eye disease (DED) who failed to respond to artificial tear sodium hyaluronate eye drops three times a day for two weeks.
The main question aims to answer are:
- How effective are stem cell eye drops in patients with DED?
- How safe are stem cell eye drops for patients with DED? Participants will be treated with mesenchymal stem cells (MSCs) eye drops, 5×10^5 /50μl in each eye, twice a day for two weeks and they will be followed up for three months after treatment.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Anticipated)
Phase
- Early Phase 1
Contacts and Locations
Study Contact
- Name: kai Hu, doctor
- Phone Number: +86 13951606283
- Email: kai_hu@nju.edu.cn
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- As determined by the investigator, the subject is able to understand and comply with the protocol requirements;
- Subject or subject's legal representative (if applicable) sign and date the written informed consent or any privacy authorization document required prior to the commencement of the study process;
- Age 40-60;
- Female patients;
The subject has received artificial tear sodium hyaluronate treatment with eye drops three times a day, but the treatment has no effect for two weeks, and the clinical examination results are consistent with:
- OSDI score ≥13;
- Schirmer test < 10mm/5min;
- Tear break-up time < 10s;
- Fluorescein sodium staining on the ocular surface was positive.
Exclusion Criteria:
Eye exclusion criteria:
- Subjects with other eye diseases such as glaucoma, cataract, uveitis, optic neuritis, etc.;
- The subjects had undergone eye surgery (e.g., cataract surgery) within the last three months;
- Subjects who wear contact lenses for a long time and are unwilling to remove them in the study;
- The subject has received eye drops in the past 24 hours that may affect the clinical study.
Exclusion criteria related to infectious diseases:
- The subject has fungal, bacterial or viral keratitis or conjunctivitis with evidence of infection;
- The subject has chronic hepatitis B virus (HBV) infection or chronic hepatitis C virus (HCV) infection;
- The subject has any identified congenital or acquired immunodeficiency (e.g., common immunodeficiency, human immunodeficiency HIV infection, organ transplantation);
- The subject has active tuberculosis (TB positive);
- Subjects receive any live vaccine within 30 days prior to screening.
Exclusion criteria for general circumstances:
- The subject is allergic to the stem cell eye drops;
- The subject has any unstable or uncontrolled cardiovascular, pulmonary, liver, kidney, gastrointestinal, urogenital, hematological, clotting, immunological, endocrine/metabolic, or other medical condition that the investigator deems to interfere with the study or endanger the safety of the subject;
- Subjects had had any surgery requiring general anesthesia within 30 days prior to enrollment, or planned to have a larger procedure during the study period surgery;
- Subjects have a history of severe neurological diseases, including stroke, multiple sclerosis, brain tumors, or neurodegenerative diseases;
- The subjects had active psychosis, which the researchers thought might interfere with their compliance with the study process;
- Lactating female subjects, or female subjects with positive serum pregnancy test results during the screening period, or positive urine pregnancy test results prior to study drug administration.
Study Plan
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: experimental group
The MSCs eye drops was administered to enrolled patients with 5×10^5 /50μl in each eye, twice a day for 2 weeks.
|
MSCs were used to prepare single-cell suspension, and 0.9% sodium chloride was added to balance PH value to prepare the effective, safe and stable eye drops.
Giving the patient with 5×10^5 /50μl in each eye, twice a day for 2 weeks.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The change of OSDI score
Time Frame: 1 week
|
OSDI questionnaire: It was divided into 3 dimensions, including ocular symptoms, visual function, and environmental factors.
The total score is less than 13.
|
1 week
|
The change of Schirmer test
Time Frame: 1 week
|
Standard tear test paper was taken and held in the conjunctival sac at 1/3 of the lower eyelid, and the patient was instructed to close the eyes gently.
The results were observed 5 minutes later.
Schirmer test < 10mm/5min was abnormal.
|
1 week
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Tear break-up time
Time Frame: 1 week
|
After staining with 0.25% fluorescein sodium, patients were instructed to close their eyes under the slit lamp microscope.
The tear film rupture time was calculated from the time of eye opening to the appearance of the first burst spot, and the mean value was taken for three consecutive tests.
The tear film rupture time < 10s is abnormal
|
1 week
|
Fluorescein sodium staining of the ocular surface.
Time Frame: 1 week
|
After staining with 0.25% fluorescein sodium, defect staining was observed under slit lamp microscope.
Cornea was scored in 3 areas (FIG. 1) : top, center and bottom.
Each area was scored according to 0 points (without any staining), 1 points (partial staining), 2 points (staining of more than half of the area) and 3 points (staining of the whole area), and the total was divided into the sum of 3 areas.
A higher score indicates more severe ocular surface damage.
|
1 week
|
Collaborators and Investigators
Publications and helpful links
General Publications
- Dana R, Bradley JL, Guerin A, Pivneva I, Stillman IO, Evans AM, Schaumberg DA. Estimated Prevalence and Incidence of Dry Eye Disease Based on Coding Analysis of a Large, All-age United States Health Care System. Am J Ophthalmol. 2019 Jun;202:47-54. doi: 10.1016/j.ajo.2019.01.026. Epub 2019 Feb 2.
- Stapleton F, Alves M, Bunya VY, Jalbert I, Lekhanont K, Malet F, Na KS, Schaumberg D, Uchino M, Vehof J, Viso E, Vitale S, Jones L. TFOS DEWS II Epidemiology Report. Ocul Surf. 2017 Jul;15(3):334-365. doi: 10.1016/j.jtos.2017.05.003. Epub 2017 Jul 20.
- Pflugfelder SC, de Paiva CS. The Pathophysiology of Dry Eye Disease: What We Know and Future Directions for Research. Ophthalmology. 2017 Nov;124(11S):S4-S13. doi: 10.1016/j.ophtha.2017.07.010.
- Oguz H. Ocular surface disease and quality of life in patients with glaucoma. Am J Ophthalmol. 2012 May;153(5):1003; author reply 1003-4. doi: 10.1016/j.ajo.2012.01.017. No abstract available.
- Baudouin C. Detrimental effect of preservatives in eyedrops: implications for the treatment of glaucoma. Acta Ophthalmol. 2008 Nov;86(7):716-26. doi: 10.1111/j.1755-3768.2008.01250.x. Epub 2008 Jun 3.
- Yamaguchi T. Inflammatory Response in Dry Eye. Invest Ophthalmol Vis Sci. 2018 Nov 1;59(14):DES192-DES199. doi: 10.1167/iovs.17-23651.
- Luo L, Li DQ, Doshi A, Farley W, Corrales RM, Pflugfelder SC. Experimental dry eye stimulates production of inflammatory cytokines and MMP-9 and activates MAPK signaling pathways on the ocular surface. Invest Ophthalmol Vis Sci. 2004 Dec;45(12):4293-301. doi: 10.1167/iovs.03-1145.
- Fan NW, Dohlman TH, Foulsham W, McSoley M, Singh RB, Chen Y, Dana R. The role of Th17 immunity in chronic ocular surface disorders. Ocul Surf. 2021 Jan;19:157-168. doi: 10.1016/j.jtos.2020.05.009. Epub 2020 May 26.
- Dohlman TH, Chauhan SK, Kodati S, Hua J, Chen Y, Omoto M, Sadrai Z, Dana R. The CCR6/CCL20 axis mediates Th17 cell migration to the ocular surface in dry eye disease. Invest Ophthalmol Vis Sci. 2013 Jun 12;54(6):4081-91. doi: 10.1167/iovs.12-11216.
- De Paiva CS, Chotikavanich S, Pangelinan SB, Pitcher JD 3rd, Fang B, Zheng X, Ma P, Farley WJ, Siemasko KF, Niederkorn JY, Stern ME, Li DQ, Pflugfelder SC. IL-17 disrupts corneal barrier following desiccating stress. Mucosal Immunol. 2009 May;2(3):243-53. doi: 10.1038/mi.2009.5. Epub 2009 Feb 25.
- Subbarayal B, Chauhan SK, Di Zazzo A, Dana R. IL-17 Augments B Cell Activation in Ocular Surface Autoimmunity. J Immunol. 2016 Nov 1;197(9):3464-3470. doi: 10.4049/jimmunol.1502641. Epub 2016 Sep 21.
- Melnikov S, Mayan H, Uchida S, Holtzman EJ, Farfel Z. Cyclosporine metabolic side effects: association with the WNK4 system. Eur J Clin Invest. 2011 Oct;41(10):1113-20. doi: 10.1111/j.1365-2362.2011.02517.x. Epub 2011 Mar 24.
- Park B, Lee IS, Hyun SW, Jo K, Lee TG, Kim JS, Kim CS. The Protective Effect of Polygonum cuspidatum (PCE) Aqueous Extract in a Dry Eye Model. Nutrients. 2018 Oct 19;10(10):1550. doi: 10.3390/nu10101550.
- Perry HD, Solomon R, Donnenfeld ED, Perry AR, Wittpenn JR, Greenman HE, Savage HE. Evaluation of topical cyclosporine for the treatment of dry eye disease. Arch Ophthalmol. 2008 Aug;126(8):1046-50. doi: 10.1001/archopht.126.8.1046.
- de Paiva CS, Pflugfelder SC, Ng SM, Akpek EK. Topical cyclosporine A therapy for dry eye syndrome. Cochrane Database Syst Rev. 2019 Sep 13;9(9):CD010051. doi: 10.1002/14651858.CD010051.pub2.
- Holland EJ, Darvish M, Nichols KK, Jones L, Karpecki PM. Efficacy of topical ophthalmic drugs in the treatment of dry eye disease: A systematic literature review. Ocul Surf. 2019 Jul;17(3):412-423. doi: 10.1016/j.jtos.2019.02.012. Epub 2019 Mar 4.
- Prockop DJ, Kota DJ, Bazhanov N, Reger RL. Evolving paradigms for repair of tissues by adult stem/progenitor cells (MSCs). J Cell Mol Med. 2010 Sep;14(9):2190-9. doi: 10.1111/j.1582-4934.2010.01151.x.
- Han Y, Yang J, Fang J, Zhou Y, Candi E, Wang J, Hua D, Shao C, Shi Y. The secretion profile of mesenchymal stem cells and potential applications in treating human diseases. Signal Transduct Target Ther. 2022 Mar 21;7(1):92. doi: 10.1038/s41392-022-00932-0.
- Prockop DJ, Oh JY. Mesenchymal stem/stromal cells (MSCs): role as guardians of inflammation. Mol Ther. 2012 Jan;20(1):14-20. doi: 10.1038/mt.2011.211. Epub 2011 Oct 18.
- Yao G, Qi J, Liang J, Shi B, Chen W, Li W, Tang X, Wang D, Lu L, Chen W, Shi S, Hou Y, Sun L. Mesenchymal stem cell transplantation alleviates experimental Sjogren's syndrome through IFN-beta/IL-27 signaling axis. Theranostics. 2019 Oct 21;9(26):8253-8265. doi: 10.7150/thno.37351. eCollection 2019.
- Li Y, Ma K, Zhang L, Xu H, Zhang N. Human Umbilical Cord Blood Derived-Mesenchymal Stem Cells Alleviate Dextran Sulfate Sodium-Induced Colitis by Increasing Regulatory T Cells in Mice. Front Cell Dev Biol. 2020 Nov 24;8:604021. doi: 10.3389/fcell.2020.604021. eCollection 2020.
- Lee MJ, Ko AY, Ko JH, Lee HJ, Kim MK, Wee WR, Khwarg SI, Oh JY. Mesenchymal stem/stromal cells protect the ocular surface by suppressing inflammation in an experimental dry eye. Mol Ther. 2015 Jan;23(1):139-46. doi: 10.1038/mt.2014.159. Epub 2014 Aug 25.
- Villatoro AJ, Fernandez V, Claros S, Rico-Llanos GA, Becerra J, Andrades JA. Use of adipose-derived mesenchymal stem cells in keratoconjunctivitis sicca in a canine model. Biomed Res Int. 2015;2015:527926. doi: 10.1155/2015/527926. Epub 2015 Feb 23.
- Sgrignoli MR, Silva DA, Nascimento FF, Sgrignoli DAM, Nai GA, da Silva MG, de Barros MA, Bittencourt MKW, de Morais BP, Dinallo HR, Foglia BTD, Cabrera WB, Fares EC, Andrade SF. Reduction in the inflammatory markers CD4, IL-1, IL-6 and TNFalpha in dogs with keratoconjunctivitis sicca treated topically with mesenchymal stem cells. Stem Cell Res. 2019 Aug;39:101525. doi: 10.1016/j.scr.2019.101525. Epub 2019 Jul 31.
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- SC202200102
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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.
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