- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01874769
Study of Immune Tolerance and Capacity for Wound Healing of Patients With Recessive Dystrophic Epidermolysis Bullosa (RDEB) (RDEB)
Recessive Dystrophic Epidermolysis Bullosa (RDEB) is one of the most severe rare inherited skin disorders affecting children and adults. Current medical care protocols for RDEB patients are limited to palliative procedures to treat blistering and erosive lesions, wounds, and severe local and systemic complications such as fusion and contracture of the digits, skin cancer, esophageal stricture, severe anemia, infections, malnutrition and growth retardation. However, current medical treatments still cannot prevent the recurrence of the lesions arising from defective expression of type VII collagen (COL7A1), the main constituent of anchoring fibrils which form essential structures for dermal-epidermal adherence.
The purpose of this study is to investigate the capacity of keratinocytes and fibroblasts to repair skin wounds in patients suffering from Recessive Dystrophic Epidermolysis Bullosa (RDEB).
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Alain Hovnanian, Prof
- Phone Number: +33 1 71 19 63 95
- Email: alain.hovnanian@inserm.fr
Study Locations
-
-
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Paris, France, 75743 Cedex 15
- Recruiting
- Service de dermatologie Necker Hospital for sick children
-
Contact:
- Christine Bodemer, Prof
-
Principal Investigator:
- Alain Hovnanian, Prof, MD, PhD
-
Paris, France, 75743/ Cedex 15
- Recruiting
- Inserm U781 Service de Génétique Necker Hospital for sick children
-
Principal Investigator:
- Alain Hovnanian, Prof, MD, PhD
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-
-
-
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London, United Kingdom, SE19RT
- Recruiting
- Guy's and ST Thomas NHS Foundation trust/Guy's Hospital
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Principal Investigator:
- John McGrath, Prof, MD, PhD
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- Confirmed molecular diagnosis of recessive dystrophic epidermolysis bullosa, established for both alleles;
- Non severe generalized clinical form of RDEB;
- Presence of type VII collagen on skin biopsy and/or western-blot analysis detected with a set of specific antibodies;
- Presence of intact skin areas without blisters, infection or erosion;
- Absence of hospitalization related to EB condition;
- Patients and their parents when applicable should be able and willing to return for follow up;
- Patients should be able and willing to give signed informed consent. For patients who are minor, informed consent will be signed by a legally authorized representative, as well as an assent form by the minor patient.
- Ability to undergo local anesthesia.
Exclusion Criteria:
Severity of disease and presence of ill-prognostic features:
- Premature termination codon in the noncollagenous (NC1) domain of COL7A1 on both alleles;
- Absence of detectable type VII collagen expression on skin biopsy and Western blot analysis from cultured cells;
Underlying conditions, diseases or active infections likely to increase the risk of complications or to interfere with the biological investigations:
- History of current or previous skin cancer (Squamous cell carcinoma or other malignant skin cancer);
- Current infectious diseases, including systemic infections and known positive HIV serology (Kaposi's sarcoma), hepatitis B and C;
- History of current psychological or psychiatric disease;
- Absence of an adequate familial and social support;
- History of current or previous organ diabetes mellitus;
- Non corrected severe anemia (Hemoglobin level: < 8 g/ml);
- Non corrected iron deficiency;
- History of significant allergy to an anaesthetic procedure
- Patient currently receiving anticoagulant or anti-aggregation treatment;
- Participation in another clinical trial or therapy protocol for RDEB at the time of study inclusion
- Positive pregnancy urinary test or lactating women
- Not affiliated to the national social security/health service beneficiary and families with beneficiary children.
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Blood collection and skin biopsies
|
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Determination of the proliferative capacity of keratinocytes and fibroblasts in characterized RDEB patients
Time Frame: Month 23
|
Populations of keratinocytes and fibroblasts isolated from punch biopsies will be analyzed for their proliferative capacity.
|
Month 23
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical evaluation and scoring
Time Frame: Month 9
|
Clinical evaluation and scoring will be assessed using The Birmingham Epidermolysis Bullosa Severity score.
|
Month 9
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Identification of COL7A1 mutations
Time Frame: Month 9
|
COL7A1 mutations will be screened by direct sequencing of peripheral blood DNA using a set of primers designed to sequence the 118 COL7A1 exons and their intronic junctions.
|
Month 9
|
Assessment of type VII collagen expression and anchoring fibrils formation in the skin
Time Frame: Month 9
|
Punch biopsies of the patient skin will be taken and processed for cell culture (keratinocytes and fibroblasts) and for histological and ultrastructural analyses.
|
Month 9
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Identification of circulating antibodies against type VII collagen and quantification of the frequency of reactive T-lymphocytes against type VII collagen
Time Frame: Month 9
|
Humoral and cytotoxic immune response against full-length type VII collagen will be assessed by ELISA and ELISPOT assays respectively.
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Month 9
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Determination of the likelihood for the patient of developing an immune response to type VII collagen
Time Frame: Month 12
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High resolution HLA genotyping will be performed from patient's DNA.
Patient prediction of non-self epitopes on WT collagen VII, based on the patient's COL7A1 mutations and their HLA typing will be performed in silico.
|
Month 12
|
Collaborators and Investigators
Investigators
- Principal Investigator: Alain Hovnanian, Prof, National Institut of health and medical research
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- C12-22
- 2012-A01051-42 (Registry Identifier: IDRCB)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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