Blood Based Eyedrops From Different Sources in the Treatment of Severe Keratopathy

NCT ID: NCT03064984

Last Updated: 2017-02-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-01-30

Study Completion Date

2017-09-30

Brief Summary

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Topical preparations (eye drops) derived from the blood have become a relatively common treatment for more advanced forms of keratopathy. The purpose of this study is to evaluate the effect of two blood components from donors (serum cord blood and serum from adult subject donor peripheral blood) in the treatment of severe keratopathies.

Detailed Description

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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.

Conditions

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Keratopathy Sjogren's Syndrome GVHD - Graft-Versus-Host Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This is a double-blind, interventional clinical study, randomized, multicenter. The treatments under study comprise topical products prepared from two different sources: umbilical cord blood collected at birth and adult subject donor peripheral blood. The products are prepared, standardized, controlled and sealed in anonymous frozen vials in the Transfusional Service, partner in the study.

The study consists of two phases: Phase 1 is runned for one month treatment. The assignment of the treatment in Phase 1 is performed through a computer based randomization process, blind to the patient and the clinician, only known to the Transfusion Service personnel. The patient enter Phase 2 only in case of a corneal epithelial damage relapse taking place within two months after the end of Phase 1, and the treatment assigned belongs to the remaining arm. In this case also, the treatment is only known to the Transfusion Service personnel, trained to keep data aside.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
The products under study are prepared, standardized, controlled and sealed in anonymous frozen vials in the Transfusional Service of the S.Orsola-Malpighi Hospital, our partner and collaborator in the study. The products have same physical and colour characteristics and cannot be visually recognized. Boxes containing the vials report a code of assignement only known by the Transfusion service personnel.

Study Groups

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CBS eyedrops

Eyedrops prepared from CBS (Cord Blood Serum), and administered 1 drop/each eye/8 times per day, for 30 days

Group Type ACTIVE_COMPARATOR

PBS eyedrops

Intervention Type OTHER

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.

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

Group Type ACTIVE_COMPARATOR

CBS eyedrops

Intervention Type OTHER

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.

Interventions

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CBS eyedrops

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.

Intervention Type OTHER

PBS eyedrops

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.

Intervention Type OTHER

Eligibility Criteria

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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 .
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Bologna

OTHER

Sponsor Role collaborator

Regione Emilia-Romagna

OTHER

Sponsor Role collaborator

Centro Nazionale Sangue

OTHER_GOV

Sponsor Role collaborator

IRCCS Azienda Ospedaliero-Universitaria di Bologna

OTHER

Sponsor Role lead

Responsible Party

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Emilio C Campos

Full Professor of Ophthalmology, Head Ophthalmology Unit, University of Bologna

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Emilio C Campos, MD

Role: PRINCIPAL_INVESTIGATOR

AOU Bologna, University of Bologna

Locations

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AOU Bologna, Ophthalmology Unit

Bologna, Bologna, Italy

Site Status RECRUITING

Ospedale S.Maria Nuova - IRCCS - Ophthalmology Unit

Reggio Emilia, Reggio Emilia, Italy

Site Status NOT_YET_RECRUITING

Ospedale degli Infermi, Ophtalmology Unit

Rimini, Rimini, Italy

Site Status NOT_YET_RECRUITING

Countries

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Italy

Central Contacts

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Emilio C Campos, MD

Role: CONTACT

+39 051 2142831

Piera Versura, BSD

Role: CONTACT

+39 051 2142850

Facility Contacts

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Emilio C Campos, MD

Role: primary

+ 390512142831

Piera Versura, BSD

Role: backup

+ 390512142850

Luigi Fontana, MD, PHD

Role: primary

+393382060005

Alessandra Brancaleoni, MD

Role: primary

+390541608692

Stefano Volanti, MD

Role: backup

+390541608692

References

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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.

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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.

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PMID: 19882589 (View on PubMed)

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.

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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.

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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.

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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.

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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.

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Reference Type BACKGROUND
PMID: 20538982 (View on PubMed)

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.

Reference Type BACKGROUND
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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.

Reference Type BACKGROUND
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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.

Reference Type BACKGROUND
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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.

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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.

Reference Type BACKGROUND
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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.

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Reference Type BACKGROUND
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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.

Reference Type DERIVED
PMID: 31744796 (View on PubMed)

Other Identifiers

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100/2016/O/Sper

Identifier Type: -

Identifier Source: org_study_id

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