Umbilical Cord Serum Versus Conventional Eyedrops

NCT04217785 | Unknown Phase 1

• 2 other identifiers: FF-2019-209GGPM-2018-052
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 3

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. 1.Not many previous clinical trials done related to UCS eye drops.
2. 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. 3.To apply the newer technology of Keratograph® 5M in DED assessment.
4. 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.

Conditions

Dry Eye Syndromes

Keywords

Umbilical Cord Serum Eyedrops; Moderate To Severe Dry Eye

Outcome Measures

Primary Outcomes (12)

• Comparison of change in corneal surface in patients treated with Umbilical Cord Serum eyedrops and conventional AT eyedrops

  Change of non-invasive tear break-up time (s) and Tear Break-up Time (s) of corneal surface from Baseline by using Oculus Keratograph-5 Machine at 4th week of eyedrop instillation.

  At 4th week of treatment

• Comparison of change in corneal surface in patients treated with Umbilical Cord Serum eyedrops and conventional AT eyedrops

  Change of non-invasive tear break-up time (s) and Tear Break-up Time (s) of corneal surface from Baseline by using Oculus Keratograph-5 Machine at 8th week of eyedrop instillation.

  At 8th week of treatment

• Comparison of meniscometry (mm) in patients treated with Umbilical Cord Serum eyedrops and conventional AT eyedrops

  Change in tear meniscus height (mm) of corneal surface from Baseline by using Oculus Keratograph-5 Machine at 4th week of eyedrop instillation.

  At 4th week of treatment

• Comparison of meniscometry (mm) in patients treated with Umbilical Cord Serum eyedrops and conventional AT eyedrops

  Change in tear meniscus height (mm) of corneal surface from Baseline by using Oculus Keratograph-5 Machine at 8th week of eyedrop instillation.

  At 8th week of treatment

• Comparison of change in corneal surface signs in patients treated with Umbilical Cord Serum eyedrops and conventional AT eyedrops

  Change of Corneal surface signs (ie punctate epithelial erosions) from Baseline based on Oxford Scale Eye Grading through slit-lamp examination at 4th week of eyedrop instillation. The grade ranges from 0-5, in which higher scores indicate worse outcome.

  At 4th week of treatment

• Comparison of change in corneal surface signs in patients treated with Umbilical Cord Serum eyedrops and conventional AT eyedrops

  Change of Corneal surface signs (ie punctate epithelial erosions) from Baseline based on Oxford Scale Eye Grading through slit-lamp examination at 8th week of eyedrop instillation. The grade ranges from 0-5, in which higher scores indicate worse outcome.

  At 8th week of treatment

• Comparison of ocular surface redness in patients treated with Umbilical Cord Serum eyedrops and conventional AT eyedrops

  Change of ocular surface redness from Baseline based on Redness Scoring using Oculus Keratograph-5 Machine at 4th week of eyedrop instillation.

  At 4th week of treatment

• Comparison of ocular surface redness in patients treated with Umbilical Cord Serum eyedrops and conventional AT eyedrops

  Change of ocular surface redness from Baseline based on Redness Scoring using Oculus Keratograph-5 Machine at 8th week of eyedrop instillation.

  At 8th week of treatment

• Comparison of change in basal tear production in patients treated with Umbilical Cord Serum eyedrops and conventional AT eyedrops

  Change of basal tear production (mm) from Baseline through Schirmer's test at 4th week of eyedrop instillation.

  At 4th week of treatment

• Comparison of change in basal tear production in patients treated with Umbilical Cord Serum eyedrops and conventional AT eyedrops

  Change of basal tear production (mm) from Baseline through Schirmer's test at 8th week of eyedrop instillation.

  At 8th week of treatment

• Comparison of dry eye symptom improvements in patients treated with Umbilical Cord Serum eyedrops and conventional AT eyedrops

  Change of dry eye symptoms from baseline based on Ocular Surface Disease Index (OSDI) score at 4th week of eyedrop instillation.

  At 4th week of treatment

• Comparison of dry eye symptom improvements in patients treated with Umbilical Cord Serum eyedrops and conventional AT eyedrops

  Change of dry eye symptoms from baseline based on Ocular Surface Disease Index (OSDI) score at 8th week of eyedrop instillation.

  At 8th week of treatment

Study Arms (2)

A-AT eye drops

ACTIVE COMPARATOR

Optive Fusion UD eye drops + Genteal lubricant gel

Drug: Optive, Ophthalmic Solution; Drug: Genteal lubricant gel

B-UCS eye drops

ACTIVE COMPARATOR

UCS eye drops + GentTeal lubricant gel

Biological: Umbilical Cord Serum eye drops; Drug: Genteal lubricant gel

Interventions

Optive, Ophthalmic Solution DRUG

6 drops per day, for 8 weeks

Also known as: Optive Fusion UD

A-AT eye drops

Umbilical Cord Serum eye drops BIOLOGICAL

UCS eye drops (6 drops per day, for 8 weeks)

B-UCS eye drops

Genteal lubricant gel DRUG

Genteal lubricant gel (2 drops per day, for 8 weeks)

A-AT eye drops; B-UCS eye drops

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• National University of Malaysia: lead

Study Sites (3)

UKM Medical Centre

Cheras, Kuala Lumpur, 56000, Malaysia

RECRUITING

National Blood Centre, Malaysia

Kuala Lumpur, Kuala Lumpur, 50400, Malaysia

ENROLLING BY INVITATION

Hospital Kuala Lumpur

Kuala Lumpur, Kuala Lumpur, 50586, Malaysia

NOT YET RECRUITING

Related Publications (39)

• Lemp MA. Report of the National Eye Institute/Industry workshop on Clinical Trials in Dry Eyes. CLAO J. 1995 Oct;21(4):221-32. No abstract available.

  PMID: 8565190 BACKGROUND

• Aggarwal S, Kheirkhah A, Cavalcanti BM, Cruzat A, Colon C, Brown E, Borsook D, Pruss H, Hamrah P. Autologous Serum Tears for Treatment of Photoallodynia in Patients with Corneal Neuropathy: Efficacy and Evaluation with In Vivo Confocal Microscopy. Ocul Surf. 2015 Jul;13(3):250-62. doi: 10.1016/j.jtos.2015.01.005. Epub 2015 Feb 20.

  PMID: 26045233 BACKGROUND

• The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007 Apr;5(2):75-92. doi: 10.1016/s1542-0124(12)70081-2.

  PMID: 17508116 BACKGROUND

• Bradley JC, Simoni J, Bradley RH, McCartney DL, Brown SM. Time- and temperature-dependent stability of growth factor peptides in human autologous serum eye drops. Cornea. 2009 Feb;28(2):200-5. doi: 10.1097/ICO.0b013e318186321e.

  PMID: 19158565 BACKGROUND

• Bron AJ, de Paiva CS, Chauhan SK, Bonini S, Gabison EE, Jain S, Knop E, Markoulli M, Ogawa Y, Perez V, Uchino Y, Yokoi N, Zoukhri D, Sullivan DA. TFOS DEWS II pathophysiology report. Ocul Surf. 2017 Jul;15(3):438-510. doi: 10.1016/j.jtos.2017.05.011. Epub 2017 Jul 20.

  PMID: 28736340 BACKGROUND

• Celebi AR, Ulusoy C, Mirza GE. The efficacy of autologous serum eye drops for severe dry eye syndrome: a randomized double-blind crossover study. Graefes Arch Clin Exp Ophthalmol. 2014 Apr;252(4):619-26. doi: 10.1007/s00417-014-2599-1. Epub 2014 Feb 25.

  PMID: 24566903 BACKGROUND

• Chiang CC, Lin JM, Chen WL, Tsai YY. Allogeneic serum eye drops for the treatment of severe dry eye in patients with chronic graft-versus-host disease. Cornea. 2007 Aug;26(7):861-3. doi: 10.1097/ICO.0b013e3180645cd7.

  PMID: 17667623 BACKGROUND

• Craig JP, Nichols KK, Akpek EK, Caffery B, Dua HS, Joo CK, Liu Z, Nelson JD, Nichols JJ, Tsubota K, Stapleton F. TFOS DEWS II Definition and Classification Report. Ocul Surf. 2017 Jul;15(3):276-283. doi: 10.1016/j.jtos.2017.05.008. Epub 2017 Jul 20.

  PMID: 28736335 BACKGROUND

• Dietrich T, Weisbach V, Seitz B, Jacobi C, Kruse FE, Eckstein R, Cursiefen C. [Manufacture of autologous serum eye drops for out-patient therapy : cooperation between ophthalmic clinic and transfusion medicine department]. Ophthalmologe. 2008 Nov;105(11):1036-8, 1040-2. doi: 10.1007/s00347-008-1692-4. German.

  PMID: 18506408 BACKGROUND

• Esquenazi S, He J, Bazan HE, Bazan NG. Use of autologous serum in corneal epithelial defects post-lamellar surgery. Cornea. 2005 Nov;24(8):992-7. doi: 10.1097/01.ico.0000160967.65953.ea.

  PMID: 16227849 BACKGROUND

• Farrand KF, Fridman M, Stillman IO, Schaumberg DA. Prevalence of Diagnosed Dry Eye Disease in the United States Among Adults Aged 18 Years and Older. Am J Ophthalmol. 2017 Oct;182:90-98. doi: 10.1016/j.ajo.2017.06.033. Epub 2017 Jul 10.

  PMID: 28705660 BACKGROUND

• Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007 May;39(2):175-91. doi: 10.3758/bf03193146.

  PMID: 17695343 BACKGROUND

• Foulks, G., Lemp, M., Jester, J., Sutphin, J., Murube, J. & Novack, G. 2007. Report of the International Dry Eye Workshop (Dews). Ocul Surf 5(2): 65-204.

  BACKGROUND

• Guo B, Lu P, Chen X, Zhang W, Chen R. Prevalence of dry eye disease in Mongolians at high altitude in China: the Henan eye study. Ophthalmic Epidemiol. 2010 Aug;17(4):234-41. doi: 10.3109/09286586.2010.498659.

  PMID: 20642346 BACKGROUND

• Hussain M, Shtein RM, Sugar A, Soong HK, Woodward MA, DeLoss K, Mian SI. Long-term use of autologous serum 50% eye drops for the treatment of dry eye disease. Cornea. 2014 Dec;33(12):1245-51. doi: 10.1097/ICO.0000000000000271.

  PMID: 25299423 BACKGROUND

• Jirsova K, Brejchova K, Krabcova I, Filipec M, Al Fakih A, Palos M, Vesela V. The application of autologous serum eye drops in severe dry eye patients; subjective and objective parameters before and after treatment. Curr Eye Res. 2014 Jan;39(1):21-30. doi: 10.3109/02713683.2013.824987. Epub 2013 Sep 27.

  PMID: 24074049 BACKGROUND

• Jones L, Downie LE, Korb D, Benitez-Del-Castillo JM, Dana R, Deng SX, Dong PN, Geerling G, Hida RY, Liu Y, Seo KY, Tauber J, Wakamatsu TH, Xu J, Wolffsohn JS, Craig JP. TFOS DEWS II Management and Therapy Report. Ocul Surf. 2017 Jul;15(3):575-628. doi: 10.1016/j.jtos.2017.05.006. Epub 2017 Jul 20.

  PMID: 28736343 BACKGROUND

• Kojima T, Ishida R, Dogru M, Goto E, Matsumoto Y, Kaido M, Tsubota K. The effect of autologous serum eyedrops in the treatment of severe dry eye disease: a prospective randomized case-control study. Am J Ophthalmol. 2005 Feb;139(2):242-6. doi: 10.1016/j.ajo.2004.08.040.

  PMID: 15733983 BACKGROUND

• Lemp MA, Crews LA, Bron AJ, Foulks GN, Sullivan BD. Distribution of aqueous-deficient and evaporative dry eye in a clinic-based patient cohort: a retrospective study. Cornea. 2012 May;31(5):472-8. doi: 10.1097/ICO.0b013e318225415a.

  PMID: 22378109 BACKGROUND

• Lopez-Garcia JS, Garcia-Lozano I, Rivas L, Gimenez C, Acera A, Suarez-Cortes T. Effects of Autologous Serum Eye Drops on Conjunctival Expression of MUC5AC in Patients With Ocular Surface Disorders. Cornea. 2016 Mar;35(3):336-41. doi: 10.1097/ICO.0000000000000726.

  PMID: 26785302 BACKGROUND

• Moh, M. O. H. M. 2009. Keputusan Muzakarah Jawatankuasa Fatwa Majlis Kebangsaan Bagi Hal Ehwal Agama Islam Malaysia Berkaitan Pengklonan Dan Art. 2nd Edition Malaysian Guidelines for Stem Cell Research and Therapy

  BACKGROUND

• Noble BA, Loh RS, MacLennan S, Pesudovs K, Reynolds A, Bridges LR, Burr J, Stewart O, Quereshi S. Comparison of autologous serum eye drops with conventional therapy in a randomised controlled crossover trial for ocular surface disease. Br J Ophthalmol. 2004 May;88(5):647-52. doi: 10.1136/bjo.2003.026211.

  PMID: 15090417 BACKGROUND

• Noda-Tsuruya T, Asano-Kato N, Toda I, Tsubota K. Autologous serum eye drops for dry eye after LASIK. J Refract Surg. 2006 Jan-Feb;22(1):61-6. doi: 10.3928/1081-597X-20060101-13.

  PMID: 16447938 BACKGROUND

• Rahman, A. a. A., Badarudin, N. E., Azemin, M. Z. C. & Ariffin, A. E. 2017. Development of a Bahasa Melayu Version of Ocular Surface Disease Index (Osdi). INTERNATIONAL JOURNAL OF ALLIED HEALTH SCIENCES 1(1):

  BACKGROUND

• Ralph RA, Doane MG, Dohlman CH. Clinical experience with a mobile ocular perfusion pump. Arch Ophthalmol. 1975 Oct;93(10):1039-43. doi: 10.1001/archopht.1975.01010020815015.

  PMID: 1180750 BACKGROUND

• Uchino M, Schaumberg DA. Dry Eye Disease: Impact on Quality of Life and Vision. Curr Ophthalmol Rep. 2013 Jun;1(2):51-57. doi: 10.1007/s40135-013-0009-1.

  PMID: 23710423 BACKGROUND

• Urzua CA, Vasquez DH, Huidobro A, Hernandez H, Alfaro J. Randomized double-blind clinical trial of autologous serum versus artificial tears in dry eye syndrome. Curr Eye Res. 2012 Aug;37(8):684-8. doi: 10.3109/02713683.2012.674609. Epub 2012 Jun 6.

  PMID: 22670856 BACKGROUND

• Wolffsohn JS, Arita R, Chalmers R, Djalilian A, Dogru M, Dumbleton K, Gupta PK, Karpecki P, Lazreg S, Pult H, Sullivan BD, Tomlinson A, Tong L, Villani E, Yoon KC, Jones L, Craig JP. TFOS DEWS II Diagnostic Methodology report. Ocul Surf. 2017 Jul;15(3):539-574. doi: 10.1016/j.jtos.2017.05.001. Epub 2017 Jul 20.

  PMID: 28736342 BACKGROUND

• Jeong, S. & Lee, S. B. 2016. Reliability of a New Non-Invasive Tear Film Break-up Time Measurement Using a Keratograph. Journal of the Korean Ophthalmological Society 57(9): 1354-1360.

  RESULT

• Mukhopadhyay S, Sen S, Datta H. Comparative role of 20% cord blood serum and 20% autologous serum in dry eye associated with Hansen's disease: a tear proteomic study. Br J Ophthalmol. 2015 Jan;99(1):108-12. doi: 10.1136/bjophthalmol-2013-304801. Epub 2014 Aug 19.

  PMID: 25138758 RESULT

• Rauz S, Koay SY, Foot B, Kaye SB, Figueiredo F, Burdon MA, Dancey E, Chandrasekar A, Lomas R. The Royal College of Ophthalmologists guidelines on serum eye drops for the treatment of severe ocular surface disease: full report. Eye (Lond). 2017 Nov 17. doi: 10.1038/eye.2017.209. Online ahead of print. No abstract available.

  PMID: 29148532 RESULT

• Rauz S, Saw VP. Serum eye drops, amniotic membrane and limbal epithelial stem cells--tools in the treatment of ocular surface disease. Cell Tissue Bank. 2010 Feb;11(1):13-27. doi: 10.1007/s10561-009-9128-1. Epub 2009 Apr 22.

  PMID: 19387867 RESULT

• Schiffman RM, Christianson MD, Jacobsen G, Hirsch JD, Reis BL. Reliability and validity of the Ocular Surface Disease Index. Arch Ophthalmol. 2000 May;118(5):615-21. doi: 10.1001/archopht.118.5.615.

  PMID: 10815152 RESULT

• Sharma N, Goel M, Velpandian T, Titiyal JS, Tandon R, Vajpayee RB. Evaluation of umbilical cord serum therapy in acute ocular chemical burns. Invest Ophthalmol Vis Sci. 2011 Feb 25;52(2):1087-92. doi: 10.1167/iovs.09-4170.

  PMID: 20538982 RESULT

• Simmons PA, Liu H, Carlisle-Wilcox C, Vehige JG. Efficacy and safety of two new formulations of artificial tears in subjects with dry eye disease: a 3-month, multicenter, active-controlled, randomized trial. Clin Ophthalmol. 2015 Apr 15;9:665-75. doi: 10.2147/OPTH.S78184. eCollection 2015.

  PMID: 25931807 RESULT

• Vajpayee RB, Mukerji N, Tandon R, Sharma N, Pandey RM, Biswas NR, Malhotra N, Melki SA. Evaluation of umbilical cord serum therapy for persistent corneal epithelial defects. Br J Ophthalmol. 2003 Nov;87(11):1312-6. doi: 10.1136/bjo.87.11.1312.

  PMID: 14609821 RESULT

• Versura P, Buzzi M, Giannaccare G, Terzi A, Fresina M, Velati C, Campos EC. Targeting growth factor supply in keratopathy treatment: comparison between maternal peripheral blood and cord blood as sources for the preparation of topical eye drops. Blood Transfus. 2016 Mar;14(2):145-51. doi: 10.2450/2015.0020-15. Epub 2015 Jul 9.

  PMID: 26192781 RESULT

• Yoon KC, Heo H, Im SK, You IC, Kim YH, Park YG. Comparison of autologous serum and umbilical cord serum eye drops for dry eye syndrome. Am J Ophthalmol. 2007 Jul;144(1):86-92. doi: 10.1016/j.ajo.2007.03.016. Epub 2007 May 9.

  PMID: 17493572 RESULT

• Yoon KC, Im SK, Park YG, Jung YD, Yang SY, Choi J. Application of umbilical cord serum eyedrops for the treatment of dry eye syndrome. Cornea. 2006 Apr;25(3):268-72. doi: 10.1097/01.ico.0000183484.85636.b6.

  PMID: 16633024 RESULT

MeSH Terms

Conditions

Dry Eye Syndromes

Interventions

Ophthalmic Solutions

Condition Hierarchy (Ancestors)

Lacrimal Apparatus Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutical Solutions; Solutions; Pharmaceutical Preparations; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Specialty Uses of Chemicals

Study Officials

• Wan Haslina Wan Abdul Halim, M.D(UKM)

  National University of Malaysia

  STUDY CHAIR

Central Study Contacts

Wan Haslina Wan Abdul Halim, M.D(UKM)

CONTACT

+6019-6679633; afifiyad@yahoo.co.uk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant Ophthalmologist-Cornea And Anterior Segment

Study Record Dates

• First Submitted: December 23, 2019
• First Posted: January 3, 2020
• Study Start: January 20, 2020
• Primary Completion: December 1, 2020
• Study Completion: May 1, 2021
• Last Updated: September 21, 2020

Record last verified: 2020-09

Locations

MY (3)