A Dose-escalation Tolerability Study of Levodopa/Carbidopa in Angelman Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 2
- 主要终点
- Maximum Dose of Levodopa/Carbidopa That Can be Tolerated (Without Any Dose Limiting Toxicity) by at Least 3 Subjects.
研究概览
简要总结
This study is designed to determine the highest dose of levodopa/carbidopa that can be tolerated without any serious side effects by children with Angelman syndrome.
It has been hypothesized that levodopa may lead to an improvement in the neurodevelopment and abnormal movements (e.g. tremors) in children with Angelman syndrome.
Data from this study will be used to design a phase II trial to determine the efficacy of levodopa in treating children with Angelman syndrome.
详细描述
Levodopa is a prodrug that "delivers" dopamine to the brain. It is usually given with carbidopa, a peripheral decarboxylase inhibitor, to increase the bioavailability of levodopa. Animal studies have suggested that levodopa can reverse the excess phosphorylation of some enzymes involved in synaptic and neuronal function, including calcium/calmodulin-dependent kinase type 2 (CaMKII).
Recently, it was shown that excess phosphorylation of CaMKII may be responsible for some of the neurological deficits seen in Angelman syndrome. Therefore, it is hypothesized that levodopa may lead to an improvement in the neurodevelopment and abnormal movements (e.g. tremors) in children with Angelman syndrome.
Although many children have used levodopa for a variety of medical conditions over the last 30 years, it has not been approved by the Food and Drug Administration (FDA) for use in children, and it has not been formally studied in children with Angelman syndrome, so we do not know what dose of levodopa is most appropriate for children with Angelman syndrome.
Therefore, the purpose of this study is to find out the highest dose of levodopa that children with Angelman syndrome can tolerate without any serious side effects.
Once we know the dose of levodopa that can be tolerated by children with Angelman syndrome, we will conduct a larger follow-up study to find out whether levodopa will lead to an improvement in their development and tremor.
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
- 4 Years 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Angelman syndrome, confirmed by molecular testing
- •Must be willing to come for research visit on 2 days, exactly 1 week apart
排除标准
- •On levodopa, carbidopa, or any dopamine agonists in the 2 weeks prior to participation
- •Other medical conditions that may be associated with developmental or cognitive delays
- •More than 2 clinical seizures per month
- •Used monoamine oxidase (MAO) inhibitors within the last 2 weeks
- •Used phenytoin within the last 2 weeks
- •Used phenothiazines, butyrophenones, and thioxanthenes within last 2 weeks
- •Hypersensitive to levodopa or carbidopa
- •Cardiovascular disease or instability
- •Respiratory diseases, including asthma, emphysema, chronic cough, and shortness of breath
- •Liver disease
- •Stomach or intestinal ulcers
- •Kidney disease
- •Hematological problems, including anemia, leucopenia, and thrombocytopenia
- •Used investigational drugs/interventions within the past three months
结局指标
主要结局
Maximum Dose of Levodopa/Carbidopa That Can be Tolerated (Without Any Dose Limiting Toxicity) by at Least 3 Subjects.
时间窗: 1 week
次要结局
未报告次要终点
研究者
Wen-Hann Tan
Attending Physician in Genetics
Boston Children's Hospital