Evaluation of the Efficacy of CANNABIDIOL on the Pruritus in Children With Hereditary Epidermolysis Bullosa
Condition: Hereditary Epidermolysis Bullosa
MeSH terms: Epidermolysis Bullosa; Pruritus
Study type: Interventional
Phase: Phase 2

Summary: 
      Hereditary epidermolysis bullosa (HEB) is a heterogeneous group of rare genetic diseases,
      characterized by fragility of the skin and mucous membranes, which results in the appearance
      of mucocutaneous bullae and erosions during minimal trauma. Pruritus is a neuropathic pain
      mainly related to activation of unmyelinated cutaneous C nerve fibers and is very common in
      patients with HEB. It is the cause of trophic disorders, aggravation of certain wounds,
      appearance of new bubbles. In addition, this chronic pruritus can also have a major
      psychological impact on the patient and his family. However, these therapies used in the
      pruritus of patients with HEB have often proven to be ineffective.

      In order to improve the quality of life of children and their families, research into new
      therapies to limit this chronic pruritus is necessary. Among phytocannabinoids, CANNABIDIOL
      (CBD) should be clearly distinguished from Delta-9-tetrahydrocannabinol (THC). Indeed, CBD is
      an "inverse" agonist of the CB2 receptor, it acts by reducing the effect of this receptor,
      while THC is an agonist of the CB1 and CB2 receptors. Thus, CBD has antipsychotic,
      anxiolytic, antiemetic, anti-inflammatory and anti-epileptic effects, unlike THC which has
      psychotic, relaxation effects, impairs cognitive function and memory. Cannabinoids are
      involved in the physiopathology in pruritus at the level of the peripheral nervous system via
      the CB1 and TRPV1 receptors, and also at the level of the central nervous system thanks to
      the CB1 and CB2 receptors. In addition, inflammation plays an important role in the
      physiopathology of pruritus and this is reduced via the activation of CB2 receptors,
      expressed in immune cells. Various studies with promising results have examined the effect of
      cannabinoids in pruritus. No serious adverse effects have been reported and the rare adverse
      effects that have been observed are reversible upon discontinuation of treatment.

      The research project seeks to estimate the efficacy of CANNABIDIOL in the pruritus of 10
      children with severe hereditary epidermolysis bullosa. Pruritus is assessed before the start
      of treatment, then after one month of taking oral treatment, three times a day. The
      effectiveness of taking the treatment will also be assessed on pain, on the impact on sleep
      and on overall quality of life. The tolerance of CANNABIDIOL will be well monitored. The
      systemic passage of CANNABIDIOL is measured during a routine blood test 1 month after
      treatment.
    

Detailed description: 
      Experimental scheme M-3 to M-1: pre-inclusion Proposal of the study and information of the
      families followed in the dermatology department during a visit as part of the care pathway.
      Explanation of protocol.

      D0: inclusion

      During conventional hospitalization or day hospitalization of the patient in the dermatology
      department for monitoring of hereditary epidermolysis bullosa (EBH) :

        -  Signature of the consent of the legal guardians after verification of the eligibility
           criteria and information given on the protocol

        -  Collection of pruritus and pain scores

        -  Clinical skin examination with measurement of the severity score of epidermolysis
           bullosa EBDASI (Epidermolysis Bullosa Disease Activity and Scarring Index).

        -  List of treatments and medical devices of the patient

        -  Quality of sleep measured by the patient or his family on a scale of 0 to 10

        -  Quality of life measured by the patient or his family via the child DLQI questionnaire

             1. st intake of CANNABIDIOL D0 to D4: 5 mg/kg/day in 3 doses (morning, noon and
                evening). on D5: If efficacy (mean VAS for pruritus <3 on D4), continue at the same
                dosage. If ineffective or partially effective (VAS pruritus ≥3) and in the event of
                good tolerance, increase to 10 mg/kg/day in 3 doses (morning, noon and evening).

      on D10: If efficacy (mean VAS pruritus <3 on D9), continue at the same dosage. If ineffective
      or partially effective (VAS pruritus ≥3), and in the event of good tolerance, increase to 20
      mg/kg/day in 3 doses (morning, noon and evening) if previous dosage at 10 mg/kg/day, or
      increase to 10 mg/kg/day if previous dosage at 5 mg/kg/day.

      In case of intolerance at D5, D10, D14 or D21: decrease to the previous dosage, or
      interruption if the dosage was 5 mg/kg/day.

      D30(+/-2): end of treatment consultation The end-of-treatment consultation takes place D30
      (+/-2) after the start of treatment.

        -  Collection of pruritus and pain scores

        -  Clinical skin examination with measurement of the EBDASI score

        -  Quality of sleep measured by the patient or his family on a scale of 0 to 10

        -  Quality of life measured by the patient or his family via the child DLQI questionnaire

        -  During a systematic blood test, collection of two more tubes for CANNABIDIOL dosage and
           a liver test

      D48 (+2): phone call by the investigating doctor to monitor the occurrence of adverse events
    

Intervention name(s): Cannabidiol
Intervention type(s): Drug
Intervention description(s): Oral solution, taken 3 times a day (morning, noon and evening), 5 mg/kg/day from day D0 to day D4. If not effective and well tolerated, dose increase : 10 mg/kg/day from day D5 to day D9, then 20 mg/kg/day from day D10 to day D29, maximum 800 mg/day
Other intervention name(s): Epidyolex
Intervention MeSH terms: Cannabidiol
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: hereditary epidermolysis bullosa; Cannabidiol; Prutitus; Pilot Study