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

Sjogren's Syndrome Clinical Trial

Official title:

Blood Based Eyedrops From Different Sources in the Treatment of Severe Keratopathy - A Randomized Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03064984
• Other study ID #: 100/2016/O/Sper
• Status: Recruiting
• Phase: N/A
• First received: February 15, 2017
• Last updated: February 22, 2017
• Start date: January 30, 2017
• Est. completion date: September 30, 2017

Study information

• Verified date: February 2017
• Source: Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi
• Contact: Emilio C Campos, MD
• Phone: +39 051 2142831
• Email: emilio.campos[@]unibo.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: September 30, 2017
• Est. primary completion date: June 30, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 .

Related Conditions & MeSH terms

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

Intervention

Other:
• 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.
• 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.

Locations

Country	Name	City	State
Italy	AOU Bologna, Ophthalmology Unit	Bologna
Italy	Ospedale S.Maria Nuova - IRCCS - Ophthalmology Unit	Reggio Emilia
Italy	Ospedale degli Infermi, Ophtalmology Unit	Rimini

Sponsors (4)

Lead Sponsor	Collaborator
Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi	Centro Nazionale Sangue, Regione Emilia-Romagna, University of Bologna

Country where clinical trial is conducted

Italy, 

References & Publications (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. — View Citation

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. Review. — View Citation

Harritshøj 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. — View Citation

López-Plandolit S, Morales MC, Freire V, Etxebarría J, Durán 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Tsubota K, Goto E, Fujita H, Ono M, Inoue H, Saito I, Shimmura S. Treatment of dry eye by autologous serum application in Sjögren's syndrome. Br J Ophthalmol. 1999 Apr;83(4):390-5. — View Citation

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. Review. — View Citation

van Setten GB, Tervo T, Tervo K, Tarkkanen A. Epidermal growth factor (EGF) in ocular fluids: presence, origin and therapeutical considerations. Acta Ophthalmol Suppl. 1992;(202):54-9. Review. — View Citation

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:s44-50. doi: 10.2450/2013.0115-13. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Variation of corneal epithelium damage	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	Variation of subjective sensation of discomfort	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