EBCBD: Evaluation of the Efficacy of CANNABIDIOL on the Pruritus in Children With Hereditary Epidermolysis Bullosa

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05651607

Collaborator

HELEBOR (Other), Fondation Apicil (Other), Lions Club International Foundation (Other)

Enrollment

Location

Arm

5.9

Anticipated Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief 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 evaluate the efficacy of CANNABIDIOL in the pruritus of 10 children with 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.

Condition or Disease	Intervention/Treatment	Phase
Hereditary Epidermolysis Bullosa	Drug: Cannabidiol	Phase 2

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

st intake of CANNABIDIOL D0 to D4: 5 mg/kg/day in 3 doses (morning, noon and evening). D5 to D9: 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).

D10 to D30: 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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Evaluation of the Efficacy of CANNABIDIOL on the Pruritus in Children With Hereditary Epidermolysis Bullosa

Anticipated Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cannabidiol (Epidyolex)	Drug: Cannabidiol Oral solution, taken 3 times a day (morning, noon and evening), 5 mg/kg/day from day D0 to day D4. If not effective, dose increase : 10 mg/kg/day from day D5 to day D9, then 20 mg/kg/day from day D10 to day D29, maximum 400 mg/day Other Names: Epidyolex

Arm

Intervention/Treatment

Experimental: Cannabidiol (Epidyolex)

Drug: Cannabidiol

Oral solution, taken 3 times a day (morning, noon and evening), 5 mg/kg/day from day D0 to day D4. If not effective, dose increase : 10 mg/kg/day from day D5 to day D9, then 20 mg/kg/day from day D10 to day D29, maximum 400 mg/day

Other Names:

Epidyolex

Outcome Measures

Primary Outcome Measures

Clinically significant decrease of pruritus VAS scores [Day 30]
Loss of at least 2 points on the mean pruritus VAS scores recorded on D27, D28 and D29 compared to the mean pruritus scores recorded on D-3, D-2 and D-1 (D0 = inclusion and start of treatment).

Secondary Outcome Measures

Decrease of pruritus VAS scores [Day 30]
Decrease of the mean pruritus VAS scores recorded on D27, D28 and D29 compared to the mean pruritus VAS scores on D-3, D-2 and D-1
Evaluation of tolerance of Cannabidiol [Day 48]
Serious and non-serious side effects
Clinically significant decrease of chronic pain scores [Day 30]
Loss of at least 2 points on the mean pain scores (VAS or FLACC according to the age of patient) recorded on D27, D28 and D29 compared to the mean pain scores recorded on D-3, D-2 and D-1 (D0 = inclusion and start of treatment).
Decrease of chronic pain scores [Day 30]
Decrease of the mean pain scores recorded on D27, D28 and D29 compared to the mean pain scores on D-3, D-2 and D-1
Decrease of pruritus VAS score during cares [Day 30]
Decrease of the mean of maximum pruritus VAS scores recorded during the last two cares before D30 compared to the mean of maximum pruritus VAS scores recorded during the last two cares before D0
Decrease of acute pain score during cares [Day 30]
Decrease of the mean of maximum acute pain scores (VAS or FLACC according to the age of patient) recorded during the last two cares before D30 compared to the mean of maximum acute pain scores recorded during the last two cares before D0
Change of quality of sleep [Day 30]
Quality of sleep measured by the patient or his family on a scale of 0 to 10 at D30 compared to D0
systemic passage of CANNABIDIOL [Day 30]
Systemic passage measured at D30 by blood test 4 hours after the morning intake and before the midday intake of CANNABIDIOL.

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Minor patient between 2 and 17 years and 10 months suffering from hereditary epidermolysis bullosa
Patient weight less than or equal to 20 kg
With pruritus not relieved by conventional treatments with mean VAS greater than or equal to 4/10 the 3 days preceding inclusion
No change in treatment or care for at least one month
Consent of parents
Affiliated to social security

Exclusion Criteria:

Hypersensitivity to the active substance or to any of the excipients (Refined sesame oil, anhydrous ethanol, sucralose, strawberry flavor, includes benzyl alcohol)
Severe renal impairment defined by GFR less than 29 ml/min
Moderate to severe hepatic impairment defined by a Child-Pugh B or C score or an AST and/or ALT level greater than 3 times normal and/or bilirubin more than 2 times normal
Known moderate to severe heart failure, defined by LVEF less than 45% and stage II to IV of the NYHA classification
Taking a tricyclic antidepressant treatment with anti-H4 antihistamine action or a neurokinin-1 receptor antagonist in the previous month
Participating to an interventional research (category 1 or 2)
Modification of at least one background treatment in the previous month
Proven pregnancy or breastfeeding patient

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hôpital Necker Enfants Malades	Paris		France	75015

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris
HELEBOR
Fondation Apicil
Lions Club International Foundation

Investigators

Study Director: Christine BODEMER, MD, PhD, Assistance Publique - Hôpitaux de Paris
Study Chair: Lara MAYRAND, Resident, Assistance Publique - Hôpitaux de Paris
Principal Investigator: Céline GRECO, MD, PhD, Assistance Publique - Hôpitaux de Paris