Effect of CBD on the GABAergic System in Patients with Fragile X Syndrome.
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 50
- 主要终点
- Short Intracortical Inhibition
研究概览
简要总结
This proposal focuses on the therapeutic relevance of the endocannabinoid (eCB) system for the treatment of Fragile-X syndrome (FXS), the primary hereditary cause of autism spectrum disorder (ASD). Although most individuals with FXS have moderate to severe intellectual disability (ID), caregivers are mainly concerned about aggressive behavior and anxiety problems, hallmark features of the condition. Concurrent lines of evidence suggest that targeting the endocannabinoid (eCB) system by administration of cannabidiol (CBD) could upregulate GABAergic functions and correct inhibitory deficits presumed responsible for the neuropsychiatric phenotype of FXS. However, the eCB system and its effect on the brain remains unexplored in FXS patients. This clinical trial aims to define the therapeutic relevance of the eCB system for FXS using a multimodal neuroimaging approach to finely characterize the acute effects of oral CBD on the principal inhibitory neurotransmitter system (GABA) in a large cohort of FXS patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Randomization and dispensing of active and control will be conducted by the research center pharmacy.
入排标准
- 年龄范围
- 7 Years 至 55 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Eligibility criteria for FXS participants will include:
- •age between 7 and 55 years, molecular diagnosis of FXS,
- •intelligence quotient (IQ) <70,
- •aberrant behavior questionnaire score (ABC-C) > 20,
- •<3 psychoactive drugs, drug stable for > 3 months.
- •Eligibility criteria for the control group:
- •18 and 55 years old,
- •be in good general health, with no history of neurological or psychiatric disorders.
- •Eligibility Criteria for all Participants:
- •A minimum weight of 60 kg;
- •no history of liver problems (A complete blood profile to measure liver enzyme levels (bilirubin, aspartate aminotransferase (AST), argininosuccinate lyase (ASL), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT)) will be obtained before randomization for all participants).
排除标准
- •The presence of an absolute contraindication to the use of TMS and MRI / MRS (ie presence of metal in the head).
- •Individuals with ALT / ASL levels greater than 3 times the upper normal baseline, or if bilirubin exceeds 2 times the upper baseline,
研究组 & 干预措施
CBD first
A single dose of CBD dose administered followed by a dose of placebo 3 weeks later.
干预措施: Placebo (Drug)
CBD first
A single dose of CBD dose administered followed by a dose of placebo 3 weeks later.
干预措施: CBD Oral Solution (eCBD system Target) (Drug)
Placebo first
A single dose of placebo dose administered followed by a dose of CBD 3 weeks later.
干预措施: CBD Oral Solution (eCBD system Target) (Drug)
Placebo first
A single dose of placebo dose administered followed by a dose of CBD 3 weeks later.
干预措施: Placebo (Drug)
结局指标
主要结局
Short Intracortical Inhibition
时间窗: Comparison between pre and 2 hours post administration of Oral CBD solution and placebo
Transcranial Magnetic Stimulation (TMS)-derived measure of Intracortical inhibition: The degree of decrease of peak-to-peak motor evoked potential (MEP) amplitude induced by the administration of a conditioning stimulus (set at 70% of resting motor threshold) 2-4 ms before the test stimulus (stimulation intensity required to produce an MEP of 1 millivolt (mV), approximately 120% of resting motor threshold)
次要结局
- Intracortical Facilitation(Comparison between pre and 2 hours post administration of Oral CBD solution and placebo)
- Gaba concentration levels(Comparison between pre and 2 hours post administration of Oral CBD solution and placebo)
研究者
Francois Corbin
Full professor, Department of biochemistry
Université de Sherbrooke