Trial of Dextromethorphan in Rett Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- Difference in EEG Spike Counts at Six Months Compared to Baseline for Each Treatment Arm.
研究概览
简要总结
Increased brain glutamate and its N-methyl-D-aspartate (NMDA) receptors found in the brain of younger Rett syndrome (RTT) patients cause toxic damage to neurons (the brain's nerve cells), and contributing to EEG spikes. Dextromethorphan (DM) acts by blocking NMDA/glutamate receptors. This study is being done to determine if DM will prevent the harmful over-stimulation of the neurons thereby reducing EEG spike activity. Treatment with DM consists of one of 3 different doses (0.25 mg/kg per day; or 2.5 mg/kg/day; or 5mg/kg/day), and aims to find out which dose if any will help improve EEG abnormalities, behavior, cognition, and reduce seizures, as well as improve breathing abnormalities, motor capabilities, bone density, and GI dysfunction.
The study will include 90 females and males with RTT, 2 years-14.99 years of age, with a mutation in the methyl CpG binding protein 2 (MECP2) gene, and spikes on EEG, with or without clinical seizures.
详细描述
Patients meeting eligibility criteria(mutation +ve and having EEG spikes), will be admitted to the Pediatric Clinical Research Unit at Johns Hopkins Hospital and will have pharmacokinetics of DM determined to establish that they are rapid metabolizers of the drug. The baseline studies on initial admission include neurological, neuropsychology,EEG, gastroenterology, Occupational and Physical therapy evaluations. If the subject is a rapid metabolizer they will be randomized to one of the three drug doses. They are contacted by telephone, weekly in the first month, and monthly thereafter. They will be examined by a neurologist at 2 weeks,1 month, and 3 months during the drug trial. At each of these visits they will also be monitored for changes in complete blood count (CBC), electrolytes, and EKG. At the end of the 6 month drug trial the patients will be readmitted to Johns Hopkins Hospital when all baseline studies are repeated. Cost of travel, hospitalization and interim tests are free to participants.
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
- None
入排标准
- 年龄范围
- 2 Years 至 15 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •those who have classic or atypical RTT with a proven mutation in the MeCP2 gene;
- •those with documented EEG evidence of spike activity who may or may not have clinical seizures;
- •subjects must be between 2years -14.99 years of age.
排除标准
- •those without an established mutation in the MeCP2 gene;
- •those who do not have EEG evidence of spike activity;
- •those with mutations in the MeCP2 gene but who have had brain resection or surgical intervention; for example, tumor, hydrocephalus, severe head trauma; or, an associated severe medical illnesses such as vasculopathies, malignancies, diabetes, thyroid dysfunction, etc;
- •those on medications that could interact with DM, e.g. monoamine oxidase (MAO) inhibitors, selective serotonin reuptake inhibitor (SSRI), sibutramine etc. to avoid a serotonin syndrome; quinidine and drugs metabolized by the Cytochrome P450 (CYP450) isoform cytochrome P450 2D6 (CYP2D6) (e.g. amiodarone, haloperidol, propafenone, thioridazine);
- •those proven to be intermediate or slow metabolizers of DM;
- •those with reported adverse reactions to DM;
- •those whose pregnancy test is positive; and,
- •those showing poor compliance with any aspect of the study;
- •foster children
研究组 & 干预措施
DM1( 0.25 mg/kg /day)
Dextromethorphan 0.25 mg/kg per day
干预措施: Dextromethorphan (Drug)
DM2 (2.5 mg/kg/day)
Dextromethorphan 2.5 mg/kg/day
干预措施: Dextromethorphan (Drug)
DM3 (5mg/kg/day)
Dextromethorphan 5mg/kg/day
干预措施: Dextromethorphan (Drug)
结局指标
主要结局
Difference in EEG Spike Counts at Six Months Compared to Baseline for Each Treatment Arm.
时间窗: Initial and 6-month post-treatment
Difference in EEG spike count means pre and 6 months post-treatment in each of three treatment groups.
次要结局
- Improvement in Receptive Language as Measured by the Mullen Scale.(Change in mean between Initial and 6-month follow-up)
- Difference in SSI Mean Score at Six Months Compared to Baseline for Each Treatment Arm.(Initial and 6 month followup)
- Mean SSI Score for Total Subjects at Baseline and 6 Months(0-6 months)
研究者
SakkuBai Naidu, M.D.
Professor of Neurology and Pediatrics
Hugo W. Moser Research Institute at Kennedy Krieger, Inc.