- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03064984
Blood Based Eyedrops From Different Sources in the Treatment of Severe Keratopathy
Blood Based Eyedrops From Different Sources in the Treatment of Severe Keratopathy - A Randomized Clinical Trial
Study Overview
Status
Intervention / Treatment
Detailed Description
The rationale for the use of eye drops prepared from the blood as a source is mainly based on their content in growth factors (Growth factors, GF), which play an important role in regulation of many processes involved in normal healing of damaged corneal epithelium . The most used product so far is the eye drop prepared from serum (Autologous Serum, AS) or from platelet-rich plasma (Plasma Rich Platelet, PRP) of peripheral blood taken from the patients themselves. More recently, treatments were introduced by homologous sources that undoubtedly offer advantages as compared to autologous sources. In particular the homologous sources show:
- not invasiveness to the patient, who could in time not like the repeated withdrawals
applicability even in patients with underlying systemic conditions. They may contain in their blood, among others, higher levels of pro-inflammatory factors, with the consequence of poor and inappropriate final product to be prepared and delivered to the eye
- reliability, since the homologous products can be prepared, controlled, also validated under the microbiological profile and standardized advance, then kept frozen until the dispensation
- conceptually unlimited availability of the product to be dispensed
- versatility of therapeutic indications, based on different GF levels which are estimated in advance
The purpose of this study is to evaluate the effect of two products derived from two different blood sources (cord blood collected at birth from placenta umbilical veins and adult subject donor peripheral blood) in the treatment of severe keratopathies.
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Emilio C Campos, MD
- Phone Number: +39 051 2142831
- Email: emilio.campos@unibo.it
Study Contact Backup
- Name: Piera Versura, BSD
- Phone Number: +39 051 2142850
- Email: piera.versura@unibo.it
Study Locations
-
-
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Bologna, Italy, 40138
- Recruiting
- AOU Bologna, Ophthalmology Unit
-
Contact:
- Emilio C Campos, MD
- Phone Number: + 390512142831
- Email: emilio.campos@unibo.it
-
Contact:
- Piera Versura, BSD
- Phone Number: + 390512142850
- Email: piera.versura@unibo.it
-
Sub-Investigator:
- Giuseppe Giannaccare, PhD
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Reggio Emilia, Italy, 42123
- Not yet recruiting
- Ospedale S.Maria Nuova - IRCCS - Ophthalmology Unit
-
Contact:
- Luigi Fontana, MD, PHD
- Phone Number: +393382060005
- Email: luigi.fontana@asmn.re.it
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Rimini, Italy, 47900
- Not yet recruiting
- Ospedale degli Infermi, Ophtalmology Unit
-
Contact:
- Alessandra Brancaleoni, MD
- Phone Number: +390541608692
- Email: alebranca@me.com
-
Contact:
- Stefano Volanti, MD
- Phone Number: +390541608692
- Email: stefanovolanti@libero.it
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- diagnosis of severe dry eye , scored as level severity 3 according to the Dry Eye WorkShop grade (DEWS, Ocular Surf 2007)
- corneal epithelial damage, stained with fluorescein as vital dye, NEI (national Eye Institute) score> 6 (estimated with imageJ software) damage coverage> 25% of total corneal area
- good general health condition
- ability to adhere to treatment and to the procedures provided by the study
Exclusion Criteria:
- concurrent treatment with hypotensive drugs
- ocular surgery in the 12 months preceding enrollment .
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: CBS eyedrops
Eyedrops prepared from CBS (Cord Blood Serum), and administered 1 drop/each eye/8 times per day, for 30 days
|
PBS eyedrops (prepared from adult peripheral blood serum) will be provided as frozen vials containing 0.8 ml of the product and will be administered at a regimen of 1 drop / 8 times day / each eye during the waking period, with the last administration to take before bedtime.
|
Active Comparator: PBS eyedrops
Eyedrops prepared from PBS (Peripheral Blood Serum) from adult donor subjects, administered 1 drop/each eye/8 times per day, for 30 days
|
CBS eyedrops (prepared from umbilical cord blood serum) will be provided as frozen vials containing 0.8 ml of the product and will be administered at a regimen of 1 drop / 8 times day / each eye during the waking period, with the last administration to take before bedtime.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Variation of corneal epithelium damage
Time Frame: 30 days
|
The effect of the treatment(s) will be evaluated by measuring the area of damaged corneal epithelium (calculated as the mm2 of damaged epithelium) after treatment as compared to baseline, and defined as 1. complete healing : no detection of damaged area; 2. Partial healing : reduction of the damaged corneal area after treatment as compared to baseline ; 3. No improvement : same damaged corneal epithelial area in mm2 at baseline and after treatment; 4. Worsening : damaged corneal epithelial area in mm2 after treatment larger than at baseline
|
30 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Variation of subjective sensation of discomfort
Time Frame: 30 days
|
The effect of the treatment(s) will be evaluated by measuring the subjective discomfort (expressed with the OSDI score) after treatment as compared to baseline and defined as 1.
Disappearance of discomfort: OSDI score < 6/100; 2. Reduction of discomfort: reduction of the OSDI score after treatment as compared to baseline ; 3. No improvement : same values for OSDI score after treatment as detected in baseline; 4. Worsening : score for OSDI score after treatment higher than that detected at baseline
|
30 days
|
Collaborators and Investigators
Investigators
- Principal Investigator: Emilio C Campos, MD, AOU Bologna, University of Bologna
Publications and helpful links
General Publications
- van Setten GB, Tervo T, Tervo K, Tarkkanen A. Epidermal growth factor (EGF) in ocular fluids: presence, origin and therapeutical considerations. Acta Ophthalmol Suppl (1985). 1992;(202):54-9. doi: 10.1111/j.1755-3768.1992.tb02169.x. No abstract available.
- Marquez De Aracena Del Cid R, Montero De Espinosa Escoriaza I. Subconjunctival application of regenerative factor-rich plasma for the treatment of ocular alkali burns. Eur J Ophthalmol. 2009 Nov-Dec;19(6):909-15. doi: 10.1177/112067210901900603.
- Ogawa Y, Okamoto S, Mori T, Yamada M, Mashima Y, Watanabe R, Kuwana M, Tsubota K, Ikeda Y, Oguchi Y. Autologous serum eye drops for the treatment of severe dry eye in patients with chronic graft-versus-host disease. Bone Marrow Transplant. 2003 Apr;31(7):579-83. doi: 10.1038/sj.bmt.1703862.
- Tsubota K, Goto E, Fujita H, Ono M, Inoue H, Saito I, Shimmura S. Treatment of dry eye by autologous serum application in Sjogren's syndrome. Br J Ophthalmol. 1999 Apr;83(4):390-5. doi: 10.1136/bjo.83.4.390.
- Lopez-Plandolit S, Morales MC, Freire V, Etxebarria J, Duran JA. Plasma rich in growth factors as a therapeutic agent for persistent corneal epithelial defects. Cornea. 2010 Aug;29(8):843-8. doi: 10.1097/ICO.0b013e3181a81820.
- 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.
- Yoon KC, You IC, Im SK, Jeong TS, Park YG, Choi J. Application of umbilical cord serum eyedrops for the treatment of neurotrophic keratitis. Ophthalmology. 2007 Sep;114(9):1637-42. doi: 10.1016/j.ophtha.2006.12.014. Epub 2007 Mar 26.
- Yoon KC, Choi W, You IC, Choi J. Application of umbilical cord serum eyedrops for recurrent corneal erosions. Cornea. 2011 Jul;30(7):744-8. doi: 10.1097/ICO.0b013e31820d850f.
- 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.
- Versura P, Profazio V, Buzzi M, Stancari A, Arpinati M, Malavolta N, Campos EC. Efficacy of standardized and quality-controlled cord blood serum eye drop therapy in the healing of severe corneal epithelial damage in dry eye. Cornea. 2013 Apr;32(4):412-8. doi: 10.1097/ICO.0b013e3182580762.
- Versura P, Buzzi M, Giannaccare G, Grillini M, Terzi A, Pagliaro P, Campos EC. Cord blood serum-based eye drops: the impact of donor haematological and obstetric factors on the variability of epidermal growth factor levels. Blood Transfus. 2014 Jan;12 Suppl 1(Suppl 1):s44-50. doi: 10.2450/2013.0115-13. Epub 2013 Oct 3.
- 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.
- van der Meer PF, Seghatchian J, de Korte D. Autologous and allogeneic serum eye drops. The Dutch perspective. Transfus Apher Sci. 2015 Aug;53(1):99-100. doi: 10.1016/j.transci.2015.05.017. Epub 2015 Jun 9.
- Espinosa A, Hjorth-Hansen H, Aasly K, Teigum I, Sivertsen G, Seghatchian J. Implementation of a standardised method for the production of allogeneic serum eye drops from regular blood donors in a Norwegian University Hospital: Some methodological aspects and clinical considerations. Transfus Apher Sci. 2015 Aug;53(1):88-91. doi: 10.1016/j.transci.2015.05.014. Epub 2015 May 19.
- Harritshoj LH, Nielsen C, Ullum H, Hansen MB, Julian HO. Ready-made allogeneic ABO-specific serum eye drops: production from regular male blood donors, clinical routine, safety and efficacy. Acta Ophthalmol. 2014 Dec;92(8):783-6. doi: 10.1111/aos.12386. Epub 2014 Mar 16.
- Adelman SF, Howett MK, Rapp F. Protease inhibitors suppress fibrinolytic activity of herpesvirus-transformed cells. J Gen Virol. 1982 May;60(Pt 1):15-24. doi: 10.1099/0022-1317-60-1-15.
- Campos E, Versura P, Buzzi M, Fontana L, Giannaccare G, Pellegrini M, Lanconelli N, Brancaleoni A, Moscardelli F, Sebastiani S, Vaselli C, Randi V. Blood derived treatment from two allogeneic sources for severe dry eye associated to keratopathy: a multicentre randomised cross over clinical trial. Br J Ophthalmol. 2020 Aug;104(8):1142-1147. doi: 10.1136/bjophthalmol-2019-314859. Epub 2019 Nov 19.
Study record dates
Study Major Dates
Study Start (Actual)
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
- Immune System Diseases
- Autoimmune Diseases
- Eye Diseases
- Joint Diseases
- Musculoskeletal Diseases
- Rheumatic Diseases
- Connective Tissue Diseases
- Arthritis
- Stomatognathic Diseases
- Mouth Diseases
- Lacrimal Apparatus Diseases
- Arthritis, Rheumatoid
- Xerostomia
- Salivary Gland Diseases
- Dry Eye Syndromes
- Sjogren's Syndrome
- Graft vs Host Disease
- Pharmaceutical Solutions
- Ophthalmic Solutions
Other Study ID Numbers
- 100/2016/O/Sper
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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