Cord Blood Serum in the Treatment of Ocular Surface Diseases

Sponsor

IRCCS Azienda Ospedaliero-Universitaria di Bologna (Other)

Overall Status

Completed

CT.gov ID

NCT01234623

Collaborator

(none)

Enrollment

Location

14.9

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Human autologous serum (AS) eye drops have been successfully used in the treatment of severe ocular surface disorders and the enhancement of corneal wound healing, due to their growth factor (GF) content. Umbilical cord serum (UCS) contains even higher GF concentrations and the objective of the study was to prove whether UCS eye drops

are effective in the healing of corneal epithelial defects.
ameliorate the painful subjective symptoms

Condition or Disease	Intervention/Treatment	Phase
Graft vs Host Disease Sjogren's Disease	Other: UCS eyedrops

Detailed Description

The regular collection and banking of cord blood remaining in the placenta after baby's delivery started in the early 1990s and was prompted by the observation that cord blood shows an immunological immaturity which allows to avoid any matching between donor-mother source and patient-recipient, it contains a number of haemopoietic progenitor and stem cells and is therefore potentially and safely useful in the field of regenerative medicine.

Cord blood collection occurs after the umbilical cord has been cut and is extracted from the fetal end of the cord. After collection, the cord blood unit bag is delivered to the lab, processed and then cryopreserved.

The main current clinical use of cord blood is allogeneic transplantation in patients suffering from severe blood diseases but physicians and researchers are making significant progresses evaluating the safety and efficacy of umbilical cord blood stem cells for therapeutic uses far beyond their uses for blood disorders.

Umbilical cord serum (UCS) contains many growth factors and especially EGF and TGF-beta1 concentrations are two-three times higher than in peripheral blood serum and much higher than in tears and is sufficient to prevent squamous metaplasia. In addition, UCS contains anti-inflammatory cytokines with protective effect.

Current therapy for SS-I and GVHD related dry eye depends upon clinical severity of the disease. From mild to progressively severe involvement of corneal epithelial damage , tear substitutes, FANS, steroids, Cyclosporin A, contact lens shields can be topically applied alone or in combination. Autologous serum eyedrops can be an option in severe cases as well, since it supplies epithelial growth factors to the healing process of epithelium.

The use of autologous serum eyedrops, however, is a controversial issues in diseases where inflammatory cytokines are present in peripheral blood, such as GVHD.

The use of cord blood serum based tear substitutes has been recently proposed in the literature for the treatment of ocular surface diseases and neurotrophic keratitis, because it contains growth factors, neurotrophic factors and essential components of tears. Moreover, serum from cord blood is readily available from cord blood banks as quality controlled product and is therefore theoretically attractive for topical use in ophthalmology.

The use of cord blood serum eyedrops as a biological preparation can display in itself efficacy features higher than the other drugs in terms of healing and anti-inflammatory properties in absence of any chemical compound.

In Italy biological products for topical use in ophthalmology to treat corneal epithelial severe defects are not available. The originality of the present study is based on the optimization and standardization of biological eyedrops prepared from cord blood serum. The efficacy and safety of the product for topical use in ocular surface diseases will be evaluated .

For the purpose, the following methods will be applied at baseline and endpoint (28 days of treatment with UCS eyedrops):

Patients' subjective symptoms evaluation by a validated questionnaire for dry eye (OSDI)
Slit Lamp examination and evaluation of Tear Film Break Up Time, corneal fluorescein staining score, conjunctival lissamine green staining score, staining will be recorded with digital photos to estimate the healing area in the follow up
Schirmer I test to evaluate tear production
Corneal sensitivity test (measured with a Cochet-Bonnet esthesiometer)
Tear osmolarity, (TearLab, TearLab S.Diego) an indicator of the ability of the patient to compensate
Tear Clearance Rate, a global indicator of tear production and tear evaporation
Tear Proteomic to evaluate tear protein profile
Corneal and Conjunctival inflammatory marker evaluation on cells collected by imprint and scraping cytology

Data will be statistically evaluated after 28 days treatment and matched vs baseline by using the descriptive statistics for paired data. Statistic outcomes will be analyzed with caution due to the non-randomized study design.

Study Design

Study Type:

Observational

Anticipated Enrollment :

30 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Pilot Phase. Cord Blood Serum in the Treatment of Ocular Surface Diseases

Study Start Date :

Feb 1, 2010

Actual Primary Completion Date :

May 1, 2011

Actual Study Completion Date :

May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
UCB eyedrops, single arm One-centre pilot study, open, non randomized.	Other: UCS eyedrops 1 ml UCS eyedrops/day topically applied 8 times/day 1 drop/eye for 28 days Other Names: no brand names, serial or code numbers

Arm

Intervention/Treatment

UCB eyedrops, single arm

One-centre pilot study, open, non randomized.

Other: UCS eyedrops

1 ml UCS eyedrops/day topically applied 8 times/day 1 drop/eye for 28 days

Other Names:

no brand names, serial or code numbers

Outcome Measures

Primary Outcome Measures

Corneal epithelial damage evaluated by fluorescein staining (micron meter squares) with digital photos [28 days treatment]
Digital photographs taken at the slit lamp will be evaluated by means of an Image Analyzer softare, to determine the area of corneal epithelial damage involved at a given stand point. Reduction of damaged area will be estimated in micron meter squares

Secondary Outcome Measures

Reduction the patients' painful subjective symptoms [28 days treatment]
Subjective symptoms will be evaluated by means of a validated Questionnaire (OSDI, Ocular Surface Disease Index) at the given stand points
Reduction the patients' painful subjective symptoms [15 days treatment]
Subjective symptoms will be evaluated by means of a validated Questionnaire (OSDI, Ocular Surface Disease Index) at the given stand points

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

to suffer from GVHD after bone marrow transplantation or SS-I
presence of permanent or transient corneal epithelial defects scored > 2 , according to DEWS severity classification
to be in a general healthy condition
signature of study consent for participation and personal data treatment.

Exclusion Criteria:

to suffer from glaucoma and being under treatment with antiglaucomatous drugs
to have received refractive surgery over the past year

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ophthalmology Unit, Dept.of Specialistic Surgery and Anesthesiological Sciences	Bologna		Italy	40138

Sponsors and Collaborators

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Investigators

Study Director: Emilio C Campos, MD, Head of Ophthalmology Unit, Dept.of Specialistic Surgery and Anesthesiological Sciences, University of Bologna, Policlinico S. Orsola-Malpighi, Pad 1 Palagi, Via Palagi 9 -40138 Bologna Italy