Clinical trial NCT04217785: Umbilical Cord Serum Versus Conventional Eyedrops
Official title: Umbilical Cord Serum Versus Conventional Eyedrops In Treatment of Moderate To Severe Dry Eye Disease: A Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Dry Eye Syndromes
Keywords: Umbilical Cord Serum Eyedrops
Moderate To Severe Dry Eye
Lead sponsor: National University of Malaysia
Sponsor class: OTHER
First posted: 2020-01-03
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Dry eye disease (DED) is a chronic ocular surface disease and the prevalence of DED has been reported as high as 50%. Recently, The international Dry Eyes Workshop II (DEWS II) defines dry eye as a "multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles". A study done by Yoon et al. on 31 patients with severe DED concluded that UCS eye drops are effective and safe in treating severe DED. Studies found that EGF, TGF-β, VEGF and vitamin A levels were significantly higher in UCS than peripheral blood serum(PBS) whereas IGF content was significantly higher in PBS than in CBS. Yoon et al. then conducted another study whereby he compared UCS to AS in treating both Sjögren syndrome and non- Sjögren syndrome patients with severe dry eyes. They concluded that UCS eye drops were more effective in decreasing symptoms and keratoepitheliopathy in severe dry eye syndrome and increasing goblet cell density in Sjögren syndrome compared with AS drops. Despite proven more effective in treating DED, serum eye drops are not yet widely manufactured due to a few reasons. This study is chosen because

1. Not many previous clinical trials done related to UCS eye drops.
2. There were only two clinical trials done before to compare the use of UCS eye drops versus conventional AT eye drops on Hansen's disease and acute ocular chemical burn injury population.
3. To apply the newer technology of Keratograph® 5M in DED assessment.
4. To initiate a proper standard operating procedure for production as well as delivery of serum eye drops which allowing out-patient treatment with serum eye drops possible.

Detailed description: This is a prospective, single- blinded randomized clinical trial conducted in University Kebangsaan Malaysia Medical Centre (UKMMC). Umbilical cord serum will be provided by Pusat Darah Negara (National Blood Centre), Malaysia. All patients from Ophthalmology Clinic in UKM Medical Centre from December 2019 till December 2021 will be involved in this study. Patients who fulfill the inclusion criteria will be included in this study. Informed consent will be taken and dry eye assessment that includes visual acuity, OSDI score, Schirmer test, NITBUT, corneal fluorescein staining, TMH and conjunctival injection. The patients will be randomised into 2 groups; AT eye drops and UCS eye drops.

Human umbilical cord blood samples will be collected from Maternity Hospital, Hospital Kuala Lumpur with assistance of the nurses from Cord Blood Collection Unit. All maternal blood samples were collected after the written informed consent from respective parents and subjected for virology screening.

National Blood Bank has a procedure for virology screening and all collected maternal umbilical cord bloods will be screened for Hep B Surface Antigen, Anti-HCV Ag/Ab, HIV Ag/Ab, Syphillis and Cytomegalovirus (CMV) IgM in Transfusion Microbiology Laborator (Accredited by ISO 15189 and CSL). Method that has been used in the screening as below:

* Hep B Surface Antigen, Anti-HCV, HIV Ag/Ab: Chemiluminescent Microparticle Immunoassay (CMIA).
* Syphilis : Carbon Antigen (Manual)
* CMV IgM : Electrochemiluminescence Immunoassay (ECLIA)

Whereas, the CB samples are screened for bacteriology screening pre and post processing to ensure sterility of the product. The serum will be discarded if any of the laboratory results are positive or reactive.

The collected cord blood (CB) will then be placed in an incubator at the collection centre until the cord blood samples are sent to National Blood Bank in an ice box with temperature logger. Once the ice box reached National Blood Bank, MLT will check the temperature logger and make sure all the temperature data within range (10-26oC) before starting the UCS serum eye drops production.

CB will be processed in Cord Blood Processing Unit within 24 hours of collection to ensure retrieval of high quality of bioactive molecules. Laboratory temperature room, humidity and oxygen will be monitored twice a day. Upon arrival at the processing laboratory, the CB will then be left at room temperature for about 2 hours to allow the CB to clot completely. After 15 minutes of centrifugation at 3,000 × g, under sterile conditions, the serum fraction will be carefully separated from the cellular fraction. Separated serum is then transferred to a tygon tube by using a sterile docking device and diluted to a 20% dilution with balanced salt solution (BSS) without any antibiotics, and finally sealed into 1-inch segment consisting of approximately 1 ml serum eye drops. The segmented UCS will then be frozen at -20oC for 3 to 6 months or at -80°C for long term storage.

For safety and quality interest, frozen segments will be transported to UKMMC blood bank using a transportation box filled with dry ice to ensure UCS are at frozen state and to maintain the quality of the product until they reach destination. From UKMMC blood bank, participants will need to bring the frozen UCS eye drops home by transporting them in a cooler box with ice packs. At home, the frozen UCS eye drops will need to be kept in domestic freezer. The frozen UCS eye drops must be thawed at room temperature prior to usage and thereafter stored in the refrigerator at 2-8°C for a maximum of 24 hours. A short instruction sheet will be provided to participants on UCS usage. There will be no porcine/bovine materials involved in the whole process.

Statistical analysis will be performed using Statistical Package for Social Science, version 20.0 (SPSS, Inc., Chicago, III., USA) for Windows. Mean value comparisons between study groups can be performed with the Student's T-test using 2 sided-analysis. Mean value comparisons for follow up can be analysed with ANOVA. Categorical characteristics can be analyzed using a Chi-square. Differences are considered statistically significant at P\<0.05.

Eligibility criteria: Inclusion Criteria:

* Moderate to severe Dry Eye Disease based on OSDI score or DED severity grading scheme
* Patients willing to participate in this study and able to provide consent
* Patients with domestic freezer at home

Exclusion Criteria:

* Infective cases
* Cases with limbal stem cells deficiency
* Patients with lid abnormalities
* Allergic to study eye drops component

Primary outcomes:
measure: Comparison of change in corneal surface in patients treated with Umbilical Cord Serum eyedrops and conventional AT eyedrops
timeFrame: At 4th week of treatment
measure: Comparison of change in corneal surface in patients treated with Umbilical Cord Serum eyedrops and conventional AT eyedrops
timeFrame: At 8th week of treatment
measure: Comparison of meniscometry (mm) in patients treated with Umbilical Cord Serum eyedrops and conventional AT eyedrops
timeFrame: At 4th week of treatment
measure: Comparison of meniscometry (mm) in patients treated with Umbilical Cord Serum eyedrops and conventional AT eyedrops
timeFrame: At 8th week of treatment
measure: Comparison of change in corneal surface signs in patients treated with Umbilical Cord Serum eyedrops and conventional AT eyedrops
timeFrame: At 4th week of treatment
measure: Comparison of change in corneal surface signs in patients treated with Umbilical Cord Serum eyedrops and conventional AT eyedrops
timeFrame: At 8th week of treatment
measure: Comparison of ocular surface redness in patients treated with Umbilical Cord Serum eyedrops and conventional AT eyedrops
timeFrame: At 4th week of treatment
measure: Comparison of ocular surface redness in patients treated with Umbilical Cord Serum eyedrops and conventional AT eyedrops
timeFrame: At 8th week of treatment
measure: Comparison of change in basal tear production in patients treated with Umbilical Cord Serum eyedrops and conventional AT eyedrops
timeFrame: At 4th week of treatment
measure: Comparison of change in basal tear production in patients treated with Umbilical Cord Serum eyedrops and conventional AT eyedrops
timeFrame: At 8th week of treatment
measure: Comparison of dry eye symptom improvements in patients treated with Umbilical Cord Serum eyedrops and conventional AT eyedrops
timeFrame: At 4th week of treatment
measure: Comparison of dry eye symptom improvements in patients treated with Umbilical Cord Serum eyedrops and conventional AT eyedrops
timeFrame: At 8th week of treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Cheras
country: Malaysia
facility: UKM Medical Centre
state: Kuala Lumpur
city: Kuala Lumpur
country: Malaysia
facility: National Blood Centre, Malaysia
state: Wilayah Persekutuan
city: Kuala Lumpur
country: Malaysia
facility: Hospital Kuala Lumpur
state: Wilayah Persekutuan
Study officials:
affiliation: National University of Malaysia
name: Wan Haslina Wan Abdul Halim, M.D(UKM)
role: STUDY_CHAIR
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