Cannabidiol in Children With Refractory Epileptic Encephalopathy: A Phase 1 Open Label Dose Escalation Study (CARE-E)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 20
- 试验地点
- 8
- 主要终点
- Albumin (g/L)
研究概览
简要总结
This study will assess the safety and tolerability of a cannabidiol-enriched Cannabis Herbal Extract in a small group of children with refractory epileptic encephalopathy. The dosage of Cannabis Herbal Extract will be gradually increased over a four month time period.
详细描述
Epileptic Encephalopathies are a group of epilepsies that develop in children. These epilepsies can cause frequent and difficult to control seizures. Because of the ongoing seizures, these epilepsies can also cause cognitive impairment and neurological impairment.
In many children with these Epileptic Encephalopathies, seizures are difficult to control with medical treatment, such as anti-convulsants or non-drug treatments like the ketogenic diet (a high fat, adequate-protein, low-carbohydrate diet). This has resulted in a need to find therapies that are effective and better tolerated for children with epileptic encephalopathies.
There is very limited data regarding the use of cannabis products in children, in particular cannabidiol-enriched cannabis oil in children with epilepsy. However, hemp oil products with high cannabidiol and low tetrahydrocannabinol ratios have been reported to provide seizure relief and cognitive improvement in children who take them.
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
- 1 Year 至 10 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 1-10 years
- •Epileptic Encephalopathy
- •A minimum of at least 1 major seizure per week or 4 major seizures per month. For the purposes of this research study, a major seizure would include atonic, tonic, clonic, tonic-clonic, major myoclonic, myoclonic astatic seizures and epileptic spasms (including infantile spasms)
- •Refractory to anticonvulsant medication as per the International League Against Epilepsy (ILAE) Definition of failing 2 appropriate anticonvulsants at therapeutic doses
- •The ability to attend appointments regularly
- •Negative pregnancy test at screening for females who have reached menarche
排除标准
- •Recent (<1 month) change in anticonvulsant therapies including anticonvulsant medications, ketogenic diet or settings on Vagal Nerve Stimulator
- •Recent (<6 months) change in intravenous immunoglobulin (IVIG) treatment
- •Initiation of ketogenic diet within 6 months (Patients must be on the ketogenic diet for at least 6 months to prevent any delayed response from the ketogenic diet affecting study results)
- •Implantation and activation of Vagal Nerve Stimulator within 12 months (Patients may have a vagal nerve stimulator for at least one year once again to prevent delayed response from the vagal nerve stimulator affecting study results)
- •Use of cannabis-based therapy within 2 months (Participants who have previously used a cannabis based therapy may be included if they have a 2 month period without use of cannabis based therapy prior to enrolment in the study)
- •Use of selective serotonin reuptake inhibitor (SSRI), tricyclic antidepressant or atypical neuroleptic medication in last month
- •Concomitant regular use of narcotics (Use of narcotics in emergency situations and supervised by a physician is allowed)
- •Initiation or dosage change of oral or injected steroids within 3 months
- •Allergy or known intolerance to any of the compounds within the study preparation
- •Inability of study participants to attend assessments on a monthly basis
- •Clinically significant cardiac, renal or hepatic disease (as assessed by the site investigator)
结局指标
主要结局
Albumin (g/L)
时间窗: Up to 6 months
Total Cholesterol and Triglyceride (mmol/L)
时间窗: Up to 6 months
Sodium, potassium, chloride, calcium, magnesium, phosphate and carbon dioxide (mmol/L)
时间窗: Up to 6 months
Clobazam and Norclobazam Levels (umol/L)
时间窗: Up to 6 months
For participants taking clobazam who become excessively sedated
Clonazepam Level (umol/L)
时间窗: Up to 6 months
For participants taking clonazepam who become excessively sedated
Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Gamma-glutamyl transferase (GGT) and Lipase (U/L)
时间窗: Up to 6 months
Weight
时间窗: Up to 6 months
Blood Urea Nitrogen (mmol/L)
时间窗: Up to 6 months
Trough Level of Concomitant Anti-Convulsants
时间窗: Up to 7 months
Measure interactions with any anti-convulsants participants may be already on
2-hour Electroencephalogram (EEG) Recording
时间窗: Up to 6 months
Blood Pressure
时间窗: Up to 6 months
Complete Blood Count (CBC) and Differential
时间窗: Up to 6 months
Urine Ketones
时间窗: Up to 6 months
For participants on the ketogenic diet
Adverse Events
时间窗: Through study completion, up to 7 months
Side effect rating scale, includes items related to sleepiness/lethargy, irritability, nausea/vomiting and diarrhea
Heart Rate
时间窗: Up to 6 months
Creatinine (umol/L)
时间窗: Up to 6 months
Total and Direct Bilirubin (umol/L)
时间窗: Up to 6 months
次要结局
- 11-nor-9-carboxy-tetrahydrocannabinol (11-nor-9-Carboxy-THC) (ng/mL)(Up to 7 months)
- Seizure Frequency Log Book(Through study completion, up to 7 months)
- Cannabidiol (CBD) (ng/mL)(Up to 7 months)
- Tetrahydrocannabinol (Δ9-THC) (ng/mL)(Up to 7 months)
- Modified Quality of Life in Children with Epilepsy Questionnaire (QOLCE)(Through study completion, up to 7 months)
研究者
Richard Huntsman
MD
University of Saskatchewan