Clinical trial NCT01874769: Study of Immune Tolerance and Capacity for Wound Healing of Patients With Recessive Dystrophic Epidermolysis Bullosa (RDEB)
Official title: Study of Immune Tolerance and Capacity for Wound Healing of Patients With Recessive Dystrophic Epidermolysis Bullosa (RDEB)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Recessive Dystrophic Epidermolysis Bullosa
Keywords: RDEB
COL7A1
Collagen VII
Lead sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Sponsor class: OTHER_GOV
First posted: 2013-06-11
Enrollment: 30
Sex: ALL
Minimum age (years): 7
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adults and children with RDEB

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).

Detailed description: In the perspective of future therapeutic interventions, which could involve protein, cellular and/or gene therapy, it is essential to investigate RDEB patients with regards to their immune tolerance to type VII collagen and their capacity of their cells for tissue reconstruction.

Eligibility criteria: 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:

  1. Premature termination codon in the noncollagenous (NC1) domain of COL7A1 on both alleles;
  2. 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:

  1. History of current or previous skin cancer (Squamous cell carcinoma or other malignant skin cancer);
  2. Current infectious diseases, including systemic infections and known positive HIV serology (Kaposi's sarcoma), hepatitis B and C;
  3. History of current psychological or psychiatric disease;
  4. Absence of an adequate familial and social support;
  5. History of current or previous organ diabetes mellitus;
  6. Non corrected severe anemia (Hemoglobin level: \< 8 g/ml);
  7. Non corrected iron deficiency;
  8. History of significant allergy to an anaesthetic procedure
  9. Patient currently receiving anticoagulant or anti-aggregation treatment;
  10. Participation in another clinical trial or therapy protocol for RDEB at the time of study inclusion
  11. Positive pregnancy urinary test or lactating women
* Not affiliated to the national social security/health service beneficiary and families with beneficiary children.

Primary outcomes:
measure: Determination of the proliferative capacity of keratinocytes and fibroblasts in characterized RDEB patients
timeFrame: Month 23
Secondary outcomes:
measure: Clinical evaluation and scoring
timeFrame: Month 9
measure: Identification of COL7A1 mutations
timeFrame: Month 9
measure: Assessment of type VII collagen expression and anchoring fibrils formation in the skin
timeFrame: Month 9
Other outcomes:
measure: Identification of circulating antibodies against type VII collagen and quantification of the frequency of reactive T-lymphocytes against type VII collagen
timeFrame: Month 9
measure: Determination of the likelihood for the patient of developing an immune response to type VII collagen
timeFrame: Month 12
Locations:
city: Paris
country: France
facility: Service de dermatologie Necker Hospital for sick children
city: Paris
country: France
facility: Inserm U781 Service de Génétique Necker Hospital for sick children
city: London
country: United Kingdom
facility: Guy's and ST Thomas NHS Foundation trust/Guy's Hospital
Study officials:
affiliation: National Institut of health and medical research
name: Alain Hovnanian, Prof
role: PRINCIPAL_INVESTIGATOR
References: