Ketamine for the Treatment of Rett Syndrome: An Exploratory Trial
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 2
- 主要终点
- Behavioral phenomena requiring intervention
研究概览
简要总结
Rett Syndrome (RTT) is a complex disorder resulting from mutations in a gene encoding the MeCP2 protein. Currently, there are no methods to fix the abnormal gene, however, animal studies suggest that the symptoms of RTT can be treated.
Ketamine is a sedative or anesthetic, depending on the dose. The drug is approved by the US Food and Drug Administration (FDA) and is commonly used in children and adults. Animal studies and case reports in humans suggest that ketamine may reduce the symptoms of Rett syndrome. The purpose of this study is to determine the safety and efficacy of ketamine for treating breathing and behavioral symptoms of RTT.
详细描述
Families will be asked to maintain current prescription medications during the expected three-month duration of the study. However, clinically indicated medication alterations will naturally be permitted and recorded.
Each participant will experience four study days, separated by about a month. On three of the study days participants will be given Ketamine, and on the other day they will be given saline placebo.
Studies will be conducted in the Cleveland Clinic's General Clinical Research Unit which is an NIH-sponsored unit designed for studies such as this. Subjects will be admitted on the first day of each study sequence, and discharged the subsequent day. Study subjects will arrive at approximately 8:00 AM. Age, weight and height will be determined and prescription medications will be recorded. Subjects will be fitted with sensors for recording respiration, heart rate and brain electrical activity (electroencephalogram, or EEG). Treatment administration will start at noon. To avoid potential effects of circadian variation, treatment administration will start at the same time for each study day in each subject. Because the half-life of Ketamine is short (t1/2 = 10-15 minutes for sedation/anesthesia), we expect participating patients to be fully recovered from any potential sedating effects of Ketamine within an hour or two.
Each subject will be randomized to receive 3 of the 5 doses of Ketamine 0.1, 0.5, 1.0, 2.0 or 4.5 mg/kg] plus placebo, for a total of 4 periods (visits). Ordering of the treatments will be randomized, with patients earlier in the study to receive lower doses of Ketamine.
The study drug will be given as a constant infusion at 0.1, 0.5, 1.0, 2.0 or 4.5 mg/kg over the course of 40 minutes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 5 Years 至 25 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Rett syndrome diagnosis based on the 2010 RTT diagnostic criteria, as determined by review of clinical records, and
- •Pathogenic mutation in the MECP2 gene, and
- •Breathing score of 3 or greater on RSBQ, and
- •Age 5-25 years.
排除标准
- •Ongoing clinical regression as determined by review of clinical records and consultation with parents, or
- •Seizure within one week of study session, or
- •Unstable systemic illness other than Rett syndrome, or
- •Clinically important variations in medication use.
研究组 & 干预措施
Placebo
Subjects will receive an intravenous infusion of normal saline over the course of 40 minutes
干预措施: Intravenous infusion (Procedure)
Ketamine
Subjects will receive intravenous infusion of a 0.1, 0.5, 1.0, 2.0 or 4.5 mg/kg dose over the course of 40 minutes
干预措施: Intravenous infusion (Procedure)
结局指标
主要结局
Behavioral phenomena requiring intervention
时间窗: From time of admission until time of discharge during any particular study visit, typically within 36 hours of admission.
Occurrence of agitation, irritability, or worsening of pre-existing symptoms.
次要结局
- Exploratory - Rett Syndrome Behavior Questionnaire (RSBQ)(On the day following study drug infusion at each visit (30 - 36 hours after admission for each visit).)