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

Primary Purpose

Hereditary Epidermolysis Bullosa

Status
Recruiting
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Cannabidiol
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hereditary Epidermolysis Bullosa focused on measuring hereditary epidermolysis bullosa, Cannabidiol, Prutitus, Pilot Study

Eligibility Criteria

2 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Hôpital Necker Enfants MaladesRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Cannabidiol (Epidyolex)

Arm Description

Outcomes

Primary Outcome Measures

Clinically significant decrease of pruritus Visual Analog Scale (VAS) scores
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). The Visual Analogue Scale (VAS) is a scale consisting of a 10cm long line and a single question. The scale is scored in a range of 0-10 with 10 representing worst imaginable pruritus.

Secondary Outcome Measures

Change of pruritus Visual Analog Scale scores
Change 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 . The scale is scored in a range of 0-10 with 10 representing worst imaginable pruritus.
Evaluation of tolerance of Cannabidiol
Serious and non-serious side effects
Clinically significant decrease of chronic pain scores
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). The Face, Legs, Activity, Cry, Consolability (FLACC) scale is a measurement used to assess pain for children between the ages of 2 months and 7 years or individuals that are unable to communicate their pain. The scale is scored in a range of 0-10 with 10 representing severe pain. The Visual Analogue Scale (VAS) is a scale consisting of a 10cm long line and a single question. The scale is scored in a range of 0-10 with 10 representing worst imaginable pain.
Change of chronic pain scores
Change of the mean pain scores (Visual Analogue Scale or Face, Legs, Activity, Cry, Consolability scale according to the age of patient) recorded on D27, D28 and D29 compared to the mean pain scores on D-3, D-2 and D-1 The Face, Legs, Activity, Cry, Consolability (FLACC) scale is a measurement used to assess pain for children between the ages of 2 months and 7 years or individuals that are unable to communicate their pain. The scale is scored in a range of 0-10 with 10 representing severe pain. The Visual Analogue Scale (VAS) is a scale consisting of a 10cm long line and a single question. The scale is scored in a range of 0-10 with 10 representing worst imaginable pain.
Change of pruritus Visual Analog Scale score during cares
Change 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. The Visual Analogue Scale (VAS) is a scale consisting of a 10cm long line and a single question. The scale is scored in a range of 0-10 with 10 representing worst imaginable pruritus.
Change of acute pain score during cares
Change 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. The Face, Legs, Activity, Cry, Consolability (FLACC) scale is a measurement used to assess pain for children between the ages of 2 months and 7 years or individuals that are unable to communicate their pain. The scale is scored in a range of 0-10 with 10 representing severe pain. The Visual Analogue Scale (VAS) is a scale consisting of a 10cm long line and a single question. The scale is scored in a range of 0-10 with 10 representing worst imaginable pain.
Change of quality of sleep
Quality of sleep measured by the patient or his family on a scale of 0 to 10, with 10 representing excellent sleep quality, at D30 compared to D0
Change of quality of life
Quality of life measured by the patient or his family via the Dermatology Life Quality Index (DLQI child) at D30 compared to D0. The Dermatology Life Quality Index (DLQI child) is scored in a range of 0-30 with 30 representing extremely important effect on the patient's quality life.
Systemic passage of CANNABIDIOL
Systemic passage measured at D30 by blood test 4 hours after the morning intake and before the midday intake of CANNABIDIOL.
Acceptability of CANNABIDIOL
Measure of acceptability: difficulty of ingesting, difficulty of using the syringe, taste

Full Information

First Posted
December 7, 2022
Last Updated
July 12, 2023
Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
HELEBOR, Fondation Apicil, Lions Club International Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT05651607
Brief Title
Evaluation of the Efficacy of CANNABIDIOL on the Pruritus in Children With Hereditary Epidermolysis Bullosa
Acronym
EBCBD
Official Title
Evaluation of the Efficacy of CANNABIDIOL on the Pruritus in Children With Hereditary Epidermolysis Bullosa
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 6, 2023 (Actual)
Primary Completion Date
January 2024 (Anticipated)
Study Completion Date
January 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
HELEBOR, Fondation Apicil, Lions Club International Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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 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 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hereditary Epidermolysis Bullosa
Keywords
hereditary epidermolysis bullosa, Cannabidiol, Prutitus, Pilot Study

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cannabidiol (Epidyolex)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Cannabidiol
Other Intervention Name(s)
Epidyolex
Intervention Description
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
Primary Outcome Measure Information:
Title
Clinically significant decrease of pruritus Visual Analog Scale (VAS) scores
Description
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). The Visual Analogue Scale (VAS) is a scale consisting of a 10cm long line and a single question. The scale is scored in a range of 0-10 with 10 representing worst imaginable pruritus.
Time Frame
Day 30
Secondary Outcome Measure Information:
Title
Change of pruritus Visual Analog Scale scores
Description
Change 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 . The scale is scored in a range of 0-10 with 10 representing worst imaginable pruritus.
Time Frame
Day 30
Title
Evaluation of tolerance of Cannabidiol
Description
Serious and non-serious side effects
Time Frame
Day 48
Title
Clinically significant decrease of chronic pain scores
Description
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). The Face, Legs, Activity, Cry, Consolability (FLACC) scale is a measurement used to assess pain for children between the ages of 2 months and 7 years or individuals that are unable to communicate their pain. The scale is scored in a range of 0-10 with 10 representing severe pain. The Visual Analogue Scale (VAS) is a scale consisting of a 10cm long line and a single question. The scale is scored in a range of 0-10 with 10 representing worst imaginable pain.
Time Frame
Day 30
Title
Change of chronic pain scores
Description
Change of the mean pain scores (Visual Analogue Scale or Face, Legs, Activity, Cry, Consolability scale according to the age of patient) recorded on D27, D28 and D29 compared to the mean pain scores on D-3, D-2 and D-1 The Face, Legs, Activity, Cry, Consolability (FLACC) scale is a measurement used to assess pain for children between the ages of 2 months and 7 years or individuals that are unable to communicate their pain. The scale is scored in a range of 0-10 with 10 representing severe pain. The Visual Analogue Scale (VAS) is a scale consisting of a 10cm long line and a single question. The scale is scored in a range of 0-10 with 10 representing worst imaginable pain.
Time Frame
Day 30
Title
Change of pruritus Visual Analog Scale score during cares
Description
Change 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. The Visual Analogue Scale (VAS) is a scale consisting of a 10cm long line and a single question. The scale is scored in a range of 0-10 with 10 representing worst imaginable pruritus.
Time Frame
Day 30
Title
Change of acute pain score during cares
Description
Change 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. The Face, Legs, Activity, Cry, Consolability (FLACC) scale is a measurement used to assess pain for children between the ages of 2 months and 7 years or individuals that are unable to communicate their pain. The scale is scored in a range of 0-10 with 10 representing severe pain. The Visual Analogue Scale (VAS) is a scale consisting of a 10cm long line and a single question. The scale is scored in a range of 0-10 with 10 representing worst imaginable pain.
Time Frame
Day 30
Title
Change of quality of sleep
Description
Quality of sleep measured by the patient or his family on a scale of 0 to 10, with 10 representing excellent sleep quality, at D30 compared to D0
Time Frame
Day 30
Title
Change of quality of life
Description
Quality of life measured by the patient or his family via the Dermatology Life Quality Index (DLQI child) at D30 compared to D0. The Dermatology Life Quality Index (DLQI child) is scored in a range of 0-30 with 30 representing extremely important effect on the patient's quality life.
Time Frame
Day 30
Title
Systemic passage of CANNABIDIOL
Description
Systemic passage measured at D30 by blood test 4 hours after the morning intake and before the midday intake of CANNABIDIOL.
Time Frame
Day 30
Title
Acceptability of CANNABIDIOL
Description
Measure of acceptability: difficulty of ingesting, difficulty of using the syringe, taste
Time Frame
Day 30

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Céline Gréco, MD, PhD
Phone
: +33 1 42 19 27 28
Email
celine.greco@aphp.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Nelly BRIAND, PhD
Phone
01 44 38 18 62
Email
nelly.briand@aphp.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christine BODEMER, MD, PhD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Lara MAYRAND, Resident
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Céline GRECO, MD, PhD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Necker Enfants Malades
City
Paris
ZIP/Postal Code
75015
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lara MAYRAND, Résident
Phone
01 44 49 40 00
Email
lara.mayrand@aphp.fr
First Name & Middle Initial & Last Name & Degree
Christine BODEMER, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35199092
Citation
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Citation
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Results Reference
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PubMed Identifier
30142706
Citation
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.
Results Reference
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PubMed Identifier
31987788
Citation
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PubMed Identifier
16874533
Citation
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.
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PubMed Identifier
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Citation
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.
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Evaluation of the Efficacy of CANNABIDIOL on the Pruritus in Children With Hereditary Epidermolysis Bullosa

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