Study of Immune Tolerance and Capacity for Wound Healing of Patients With Recessive Dystrophic Epidermolysis Bullosa (RDEB)

NCT01874769 | Completed DMC

• 2 other identifiers: C12-222012-A01051-42
• Study Type: observational
• Target: 30
• Locations: 2 countries
• Sites: 3

Brief Summary

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).

Conditions

Recessive Dystrophic Epidermolysis Bullosa

Keywords

RDEB; COL7A1; Collagen VII

Outcome Measures

Primary Outcomes (1)

• Determination of the proliferative capacity of keratinocytes and fibroblasts in characterized RDEB patients

  Populations of keratinocytes and fibroblasts isolated from punch biopsies will be analyzed for their proliferative capacity.

  Month 23

Secondary Outcomes (3)

• Clinical evaluation and scoring

  Month 9

• Identification of COL7A1 mutations

  Month 9

• Assessment of type VII collagen expression and anchoring fibrils formation in the skin

  Month 9

Other Outcomes (2)

• Identification of circulating antibodies against type VII collagen and quantification of the frequency of reactive T-lymphocytes against type VII collagen

  Month 9

• Determination of the likelihood for the patient of developing an immune response to type VII collagen

  Month 12

Study Arms (1)

Blood collection and skin biopsies

Other: Blood collection; Other: Skin biopsies

Interventions

Blood collection OTHER

* 5 ml of blood on dry tube: Verification of the absence of auto-antibodies to type VII collagen. * 10 ml of blood sample on heparin: Verification of the absence of circulating reactive T-Lymphocytes clones to type VII collagen * 5 ml of Blood samples on ethylenediaminetetraacetic acid (EDTA): HLA genotyping of patient selected on the clinical and molecular criteria.

Blood collection and skin biopsies

Skin biopsies OTHER

* A 5-mm punch skin biopsy in the groin region performed under local anaesthesic will be undertaken during visit 1. * During the second visit, two additional 5-mm punch skin biopsies will be taken to assess stem cells proliferative capacity in 10 shortlisted patients

Blood collection and skin biopsies

Eligibility Criteria

• Age: 7 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adults and children with RDEB

You may qualify if:

• 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.

You may not qualify if:

• 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;
• Positive pregnancy urinary test or lactating women
• Not affiliated to the national social security/health service beneficiary and families with beneficiary children.

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead

Study Sites (3)

Service de dermatologie Necker Hospital for sick children

Paris, 75743 Cedex 15, France

Location

Inserm U781 Service de Génétique Necker Hospital for sick children

Paris, 75743/ Cedex 15, France

Location

Guy's and ST Thomas NHS Foundation trust/Guy's Hospital

London, SE19RT, United Kingdom

Location

Related Publications (1)

• Gaucher S, Lwin SM, Titeux M, Abdul-Wahab A, Pironon N, Izmiryan A, Miskinyte S, Ganier C, Duchatelet S, Mellerio JE, Bourrat E, McGrath JA, Hovnanian A. EBGene trial: patient preselection outcomes for the European GENEGRAFT ex vivo phase I/II gene therapy trial for recessive dystrophic epidermolysis bullosa. Br J Dermatol. 2020 Mar;182(3):794-797. doi: 10.1111/bjd.18559. Epub 2019 Nov 27. No abstract available.

  PMID: 31557321 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

All patients will have a blood sample of 5 ml on EDTA, 10 ml on heparin and 5 ml on dry tube collected for genomic DNA extraction to identify or verify COL7A1 mutations: mutation screening of the patients will be performed to identify COL7A1 mutations on both alleles. 2) HLA genotyping: patients selected on the clinical and molecular criteria will be HLA-genotyped by PCR to determine the likelihood of an immune response to the type VII collagen wild-type protein. A 5-mm punch skin biopsy performed under local anaesthesic will be undertaken during visit 1 for diagnostic purposes .The consequences of COL7A1 mutations on collagen VII protein expression will be determined, if not performed previously. Two additional 5-mm punch skin biopsies will be taken from different areas from up to 10 patients during the second visit. Keratinocytes and fibroblasts will be expanded and stored in vapor-phase liquid-nitrogen.

MeSH Terms

Conditions

Epidermolysis Bullosa Dystrophica

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Epidermolysis Bullosa; Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Collagen Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Skin Diseases, Vesiculobullous

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Alain Hovnanian, Prof

  National Institut of health and medical research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2013
• First Posted: June 11, 2013
• Study Start: August 1, 2013
• Primary Completion: August 1, 2017
• Study Completion: August 1, 2017
• Last Updated: March 3, 2026

Record last verified: 2025-01

Locations

GB (1); FR (2)