Evaluation of the Efficacy of CANNABIDIOL on the Pruritus in Children With Hereditary Epidermolysis Bullosa
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Clinically significant decrease of pruritus Visual Analog Scale (VAS) scores
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
研究组 & 干预措施
Cannabidiol (Epidyolex)
干预措施: Cannabidiol (Drug)
结局指标
主要结局
Clinically significant decrease of pruritus Visual Analog Scale (VAS) scores
时间窗: 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). 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.
次要结局
- Clinically significant decrease of chronic pain scores(Day 30)
- Change of pruritus Visual Analog Scale scores(Day 30)
- Systemic passage of CANNABIDIOL(Day 30)
- Evaluation of tolerance of Cannabidiol(Day 48)
- Change of quality of sleep(Day 30)
- Change of chronic pain scores(Day 30)
- Acceptability of CANNABIDIOL(Day 30)
- Change of pruritus Visual Analog Scale score during cares(Day 30)
- Change of acute pain score during cares(Day 30)
- Change of quality of life(Day 30)