Graft vs Host DiseaseNCT01234623
Cord Blood Serum in the Treatment of Ocular Surface Diseases
An observational study of Graft vs Host Disease and Sjogren's Disease, run by IRCCS Azienda Ospedaliero-Universitaria di Bologna at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Graft vs Host Disease, Sjogren's Disease
- What is being tested?
- UCS eyedrops
- How many people
- 30 participants
- Where
- 1 siteItaly
- Study dates
- Feb 2010to May 2011
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adult outpatients suffering from ocular surface discomfort and recurrent or permanent corneal epithelial defects
Who may be able to join
- 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.
Who cannot join
- to suffer from glaucoma and being under treatment with antiglaucomatous drugs
- to have received refractive surgery over the past year
Trial locations and contacts
1 site in 1 country.
Italy1 site
Ophthalmology Unit, Dept.of Specialistic Surgery and Anesthesiological Sciences
Bologna, Bologna, 40138
About this study
Official title: Pilot Phase. Cord Blood Serum in the Treatment of Ocular Surface Diseases
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
Read the 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.
- Conditions
- Graft vs Host Disease, Sjogren's Disease
- Being tested
- UCS eyedrops
- Keywords
- Umbilical cord serum, eyedrops, GVHD, SS-I, corneal healing
- Medical subject headings
- Graft vs Host Disease, Sjogren's Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UCS eyedropsOther
Also called no brand names, serial or code numbers
1 ml UCS eyedrops/day topically applied 8 times/day 1 drop/eye for 28 days
| Study group | Role | What they receive |
|---|---|---|
| UCB eyedrops, single arm | One-centre pilot study, open, non randomized. Receives: Other: UCS eyedrops |
What is being measured
The primary outcome is the main question the study is designed to answer.
Corneal epithelial damage evaluated by fluorescein staining (micron meter squares) with digital photos
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
Measured: 28 days treatment
Secondary outcomes (2)
Reduction the patients' painful subjective symptoms
Subjective symptoms will be evaluated by means of a validated Questionnaire (OSDI, Ocular Surface Disease Index) at the given stand points
Measured: 28 days treatment
Reduction the patients' painful subjective symptoms
Subjective symptoms will be evaluated by means of a validated Questionnaire (OSDI, Ocular Surface Disease Index) at the given stand points
Measured: 15 days treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2010 (estimated)
- Study startFeb 2010
- Primary completionMay 2011
- Study completionMay 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Graft vs Host DiseaseStudies of the same condition, open and under way.
- More trials run by IRCCS Azienda Ospedaliero-Universitaria di BolognaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Investigators
- Emilio C Campos, MD, Study director, 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
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01234623
- Sponsor's protocol ID
- EudraCT: 2008-005757-38
- Status last verified
- Apr 2011
- First submitted
- 12 Oct 2010
- Last updated
- 26 May 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Buzzi M, Versura P, Vaselli C, Coslovi C, Terzi A, Bontadini A, Campos EC. Fattori di crescita epiteliali nel sangue cordonale. SIES 2008, Bari 24-26 settembre 2008, abstract
P. Versura, V. Profazio, L. Foroni, M. Buzzi, A. Stancari, EC Campos. Cord blood serum eye drops in the treatment of ocular surface diseases in GVHD patients. A pilot study. 6th International Conference on the Tear Film & Ocular Surface: Basic Science and Clinical Relevance, Florence , September 22-25, 2010 Abstract
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.
PubMed 22955120
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Phase. Cord Blood Serum in the Treatment of Ocular Surface Diseases
- ClinicalTrials.gov ID
- NCT01234623
- Acronym / sponsor ID
- EudraCT: 2008-005757-38
- Conditions
- Graft vs Host Disease, Sjogren's Disease
- Keywords
- Umbilical cord serum, eyedrops, GVHD, SS-I, corneal healing
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- IRCCS Azienda Ospedaliero-Universitaria di BolognaUniversity, hospital or other
- Study start
- Feb 2010
- Primary completion
- May 2011 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 4 Nov 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| UCB eyedrops, single arm | – | Other: UCS eyedropsOne-centre pilot study, open, non randomized. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adult outpatients suffering from ocular surface discomfort and recurrent or permanent corneal epithelial defects
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (2 listed)
- to suffer from glaucoma and being under treatment with antiglaucomatous drugs
- to have received refractive surgery over the past year
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| UCS eyedropsAlso: no brand names, serial or code numbers1 ml UCS eyedrops/day topically applied 8 times/day 1 drop/eye for 28 days | Other | UCB eyedrops, single arm |
Primary outcome
Corneal epithelial damage evaluated by fluorescein staining (micron meter squares) with digital photos
Time frame: 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
2 secondary outcomes
Reduction the patients' painful subjective symptoms
Time frame: 28 days treatment
Reduction the patients' painful subjective symptoms
Time frame: 15 days treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 May 2011.
- BackgroundBuzzi M, Versura P, Vaselli C, Coslovi C, Terzi A, Bontadini A, Campos EC. Fattori di crescita epiteliali nel sangue cordonale. SIES 2008, Bari 24-26 settembre 2008, abstract
- Results publicationP. Versura, V. Profazio, L. Foroni, M. Buzzi, A. Stancari, EC Campos. Cord blood serum eye drops in the treatment of ocular surface diseases in GVHD patients. A pilot study. 6th International Conference on the Tear Film & Ocular Surface: Basic Science and Clinical Relevance, Florence , September 22-25, 2010 Abstract
- Derived from this study: PubMed 22955120Versura 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Emilio C Campos, MD study director
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
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Graft vs Host Disease and Sjogren's Disease, run by IRCCS Azienda Ospedaliero-Universitaria di Bologna at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 May 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Corneal epithelial damage evaluated by fluorescein staining (micron meter squares) with digital photos (time frame: 28 days treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01234623, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 May 2011.