A Double-Blind, Placebo-Controlled, Parallel-Group Study of Cannabidiol Plus Tetrahydrocannabinol (CBD+THC) Given as Adjunctive Therapy in Patients With Refractory Seizures
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 17
- 试验地点
- 2
- 主要终点
- Frequency of convulsive seizures
研究概览
简要总结
The purpose of this study is to examine whether a low dose of CBD+THC will decrease the frequency of convulsive seizures in adults with drug-resistant epilepsy, when used in addition to standard anti-epileptic drugs (AEDs). This study will also study the genes associated with epilepsy and whether different epileptic syndromes respond to treatment with CBD+THC.
详细描述
Background: Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are the two major compounds found in the cannabis plant. Reports from patients, families, and the scientific community suggest that CBD (when used as an add-on therapy) decreases the number of convulsive seizures in children and adults with Dravet syndrome, Lennox-Gastaut syndrome, and Tuberous sclerosis complex.
Trial design: Phase III, double-blind, randomized, placebo-controlled, parallel-group trial, followed by an open phase where treatment allocation will be revealed and all participants will either continue or begin receiving the active study drug.
Participants: Adults (18 years of age and older) with drug-resistant epilepsy, including patients with Dravet and Lennox Gastaut syndromes, and patients with frequent convulsive seizures (e.g., tonic, tonic-clonic, atonic, drop attacks, and focal motor seizures).
Interventions: Capsules containing a ratio of 16 CBD: 1 THC oil at a maximum total daily dose of approximately 300 mg of CBD per day, divided into equal doses in the morning and evening.
Comparator: Placebo capsules containing high-oleic sunflower oil and no active or medicinal ingredients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of epilepsy according to the ILAE classification.
- •At least 4 motor seizures per month at the start of the study, despite treatment with at least two different anti-epileptic drugs (given concurrently or sequentially) for at least one year.
- •At least 4 motor seizures per month during the prospective baseline phase (4 weeks) with no 21-day seizure free periods.
- •Stable dose(s) of the same AED(s) for one month prior to screening.
- •Agrees not to take any cannabinoids during the study or any other investigational compound for one month before the study or outside cannabinoids during the study.
- •Is planning to stay in Canada for the duration of the trial.
- •Is able to travel to one of the study sites for in-person visits with the study physicians and to a local lab for blood collection.
- •Has access to telephone, computer, and internet for regular correspondence and to complete the study questionnaires.
排除标准
- •Participation in a study involving administration of an investigational compound within one month of Visit
- •Evidence of clinically significant non-epileptic disease (cardiac, respiratory, gastrointestinal, hepatic, hematologic, or renal disease, etc.) that in the opinion of the investigators could affect the patient's safety or trial conduct.
- •Progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors.
- •Occurrence of psychogenic seizures in the previous year.
- •History of drug misuse/abuse (other than cannabinoids). Consideration may be given to allowing inclusion of subjects with remote history of drug abuse (within a defined relevant time period).
- •Multiple drug allergies (dermatological, hematological, or organ toxicity) or more than one severe drug reaction(s).
- •Pregnancy, breastfeeding.
- •Known or suspected hypersensitivity to cannabinoids, or any of the excipients of the investigational medicinal product.
- •Patients with a history of major depression, suicidal ideation or attempted suicide, schizophrenia or any other psychotic disorder, patients with a family history of schizophrenia.
研究组 & 干预措施
Medical cannabis
Capsules containing cannabis extract, dissolved in high-oleic sunflower oil, and CBD/THC in a 16:1 ratio.
干预措施: Medical Cannabis (Drug)
Placebo Control
Capsules containing a high-oleic sunflower oil, calorie-equated to the active treatment. There will be no active compounds in the placebo treatment.
Following treatment with placebo, all participants in this group will begin treatment with medical cannabis.
干预措施: Placebo (Drug)
结局指标
主要结局
Frequency of convulsive seizures
时间窗: 0 - 10 weeks
次要结局
- Changes in quality of life from baseline to end of treatment as assessed by the Quality of Life in Epilepsy Inventory (QOLIE-31) questionnaire(0 - 10 weeks)
- Changes in blood levels of AEDs from baseline to end of treatment(0 - 10 weeks)
- Changes in blood levels of liver enzymes AST, ALT, and GGT from baseline to end of treatment(0 - 10 weeks)
- Changes in quality of life from baseline to end of treatment as assessed by the Quality of Life Childhood Epilepsy (QOLCE) questionnaire(0 - 10 weeks)
- Change in caregiver's impression of change from baseline to end of treatment as assessed by the Caregiver's Global Impression of Change (CGIC) scale(0 - 10 weeks)
- Changes in blood levels of CBD and THC from baseline to end of treatment(0 - 10 weeks)
- Number of participants with treatment-related adverse events as assessed by the adverse events questionnaire(0- 10 weeks)
- Changes in functional impairment from baseline to end of treatment as assessed by the Sheehan Disability Scale (SDS)(0 - 10 weeks)
- Changes in quality of life from baseline to end of treatment as assessed by the World Health Organization Quality of Life-BREF (WHOQOL-BREF) questionnaire(0 - 10 weeks)
- Changes in symptoms of depression from baseline to end of treatment as assessed by the Quick Inventory of Depressive Symptoms (QIDS)(0 - 10 weeks)
- Change in quality of sleep from baseline to end of treatment as assessed by the Pittsburgh Sleep Quality Index (PSQI)(0 - 10 weeks)
- Changes in psychological symptoms from baseline to end of treatment as assessed by the Brief Symptom Inventory (BSI-53)(0 - 10 weeks)
- Changes in symptoms of depression from baseline to end of treatment as assessed by the Neurological Disorder Depression Inventory for Epilepsy (NDDI-E)(0 - 10 weeks)
- Changes in symptoms of anxiety from baseline to end of treatment as assessed by the Generalized Anxiety Disorder 7-item (GAD-7)(0 - 10 weeks)
- Change in overall severity of epilepsy from baseline to end of treatment as assessed by the Global Analysis of Severity of Epilepsy Scale (GASE)(0 - 10 weeks)
- Change in participant's impression of change from baseline to end of treatment as assessed by the Patients' Global Impression of Change (PGIC) scale(0 - 10 weeks)