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

NCT ID: NCT05651607

Last Updated: 2025-10-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-07
• Study Completion Date: 2023-11-17

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 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

Conditions

Hereditary Epidermolysis Bullosa

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cannabidiol (Epidyolex)

Group Type: EXPERIMENTAL

Cannabidiol

Intervention Type: DRUG

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

Interventions

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 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

Intervention Type: DRUG

Other Intervention Names

Epidyolex

Eligibility Criteria

Inclusion Criteria

• Minor patient between 2 and 17 years and 10 months
• Suffering from distrophic recessive epidermolysis bullosa
• Patient weight less than or equal to 40 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)
• Consumption of cannabis or cannabidiol
• 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
• with clinically or ultrasound sign(s) of moderate to severe cardiac insufficiency, 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
• Patient deprived of their liberty by decision of a judicial or administrative authority (Article L. 1121-6 of the Public Health Code)

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

HELEBOR

UNKNOWN

Sponsor Role: collaborator

Fondation Apicil

OTHER

Sponsor Role: collaborator

Lions Club International Foundation

OTHER

Sponsor Role: collaborator

URC-CIC Paris Descartes Necker Cochin

OTHER

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christine BODEMER, MD, PhD

Role: STUDY_DIRECTOR

Assistance Publique - Hôpitaux de Paris

Lara MAYRAND, Resident

Role: STUDY_CHAIR

Assistance Publique - Hôpitaux de Paris

Céline GRECO, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Hôpital Necker Enfants Malades

Paris, , France

Countries

France

References

Sivesind TE, Maghfour J, Rietcheck H, Kamel K, Malik AS, Dellavalle RP. Cannabinoids for the Treatment of Dermatologic Conditions. JID Innov. 2022 Jan 13;2(2):100095. doi: 10.1016/j.xjidi.2022.100095. eCollection 2022 Mar.

Reference Type: BACKGROUND

PMID: 35199092 (View on PubMed)

Sheriff T, Lin MJ, Dubin D, Khorasani H. The potential role of cannabinoids in dermatology. J Dermatolog Treat. 2020 Dec;31(8):839-845. doi: 10.1080/09546634.2019.1675854. Epub 2019 Oct 10.

Reference Type: BACKGROUND

PMID: 31599175 (View on PubMed)

Eagleston LRM, Kalani NK, Patel RR, Flaten HK, Dunnick CA, Dellavalle RP. Cannabinoids in dermatology: a scoping review. Dermatol Online J. 2018 Jun 15;24(6):13030/qt7pn8c0sb.

Reference Type: BACKGROUND

PMID: 30142706 (View on PubMed)

Avila C, Massick S, Kaffenberger BH, Kwatra SG, Bechtel M. Cannabinoids for the treatment of chronic pruritus: A review. J Am Acad Dermatol. 2020 May;82(5):1205-1212. doi: 10.1016/j.jaad.2020.01.036. Epub 2020 Jan 25.

Reference Type: BACKGROUND

PMID: 31987788 (View on PubMed)

Stander S, Reinhardt HW, Luger TA. [Topical cannabinoid agonists. An effective new possibility for treating chronic pruritus]. Hautarzt. 2006 Sep;57(9):801-7. doi: 10.1007/s00105-006-1180-1. German.

Reference Type: BACKGROUND

PMID: 16874533 (View on PubMed)

Okusanya BO, Asaolu IO, Ehiri JE, Kimaru LJ, Okechukwu A, Rosales C. Medical cannabis for the reduction of opioid dosage in the treatment of non-cancer chronic pain: a systematic review. Syst Rev. 2020 Jul 28;9(1):167. doi: 10.1186/s13643-020-01425-3.

Reference Type: BACKGROUND

PMID: 32723354 (View on PubMed)

Schrader NHB, Gorell ES, Stewart RE, Duipmans JC, Harris N, Perez VA, Tang JY, Wolff AP, Bolling MC. Cannabinoid use and effects in patients with epidermolysis bullosa: an international cross-sectional survey study. Orphanet J Rare Dis. 2021 Sep 6;16(1):377. doi: 10.1186/s13023-021-02010-0.

Reference Type: BACKGROUND

PMID: 34488820 (View on PubMed)

Chelliah MP, Zinn Z, Khuu P, Teng JMC. Self-initiated use of topical cannabidiol oil for epidermolysis bullosa. Pediatr Dermatol. 2018 Jul;35(4):e224-e227. doi: 10.1111/pde.13545. Epub 2018 May 22.

Reference Type: BACKGROUND

PMID: 29786144 (View on PubMed)

Schrader NHB, Duipmans JC, Molenbuur B, Wolff AP, Jonkman MF. Combined tetrahydrocannabinol and cannabidiol to treat pain in epidermolysis bullosa: a report of three cases. Br J Dermatol. 2019 Apr;180(4):922-924. doi: 10.1111/bjd.17341. Epub 2018 Nov 14.

Reference Type: BACKGROUND

PMID: 30347109 (View on PubMed)

Welponer T, Diem A, Nahler G, Laimer M. Purified oral cannabidiol for pain management in severe recessive dystrophic epidermolysis bullosa. Indian J Dermatol Venereol Leprol. 2022 May-Jun;88(4):551-552. doi: 10.25259/IJDVL_71_2021. No abstract available.

Reference Type: BACKGROUND

PMID: 35593277 (View on PubMed)

Other Identifiers

2022-003411-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

APHP220741

Identifier Type: -

Identifier Source: org_study_id