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

Study Overview
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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.

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

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

Intervention / Treatment
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* Other: CBS eyedrops
* Other: PBS eyedrops


Participation Criteria
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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 .

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CBS eyedrops<br>Eyedrops prepared from CBS (Cord Blood Serum), and administered 1 drop/each eye/8 times per day, for 30 days | Other: PBS eyedrops<br>* 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.<br>|
| Active Comparator: PBS eyedrops<br>Eyedrops prepared from PBS (Peripheral Blood Serum) from adult donor subjects, administered 1 drop/each eye/8 times per day, for 30 days | Other: CBS eyedrops<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |