Placebo Controlled Trial of Dextromethorphan in Rett Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 57
- 试验地点
- 1
- 主要终点
- Change in Mullen; Visual Reception Sub-scale Scores, Pre- and Post-Intervention
研究概览
简要总结
Dr. Sakkubai Naidu, Principal Investigator, is initiating a double blinded placebo controlled clinical drug trial using dextromethorphan (DM) in Rett Syndrome (RTT), at the Pediatric Clinical Research Unit (PCRU) of the Johns Hopkins Hospital/Kennedy Krieger Institute. Funding source , FDA-00PD
It has been shown that receptors for a certain brain chemical called glutamate, in particular the NMDA type, are increased in the brain of young RTT patients (<10 years of age). This chemical and its receptors, when in excess, cause harmful over-stimulation of nerve cells in the brain, contributing in part to the seizures, behavioral problems, and learning disabilities in RTT.
The investigators propose to initiate a specific treatment using DM to counter/block the effects of this brain chemical and its excessive receptors to improve the ill effects of increased glutamate/NMDA receptors, because of DM's identified ability to block NMDA receptors. DM is available for human consumption. Infants and children with respiratory infections and cough, as well as non-ketotic hyperglycinemia, are treated with DM, which has been well tolerated.
详细描述
The study will last for 3 months and will be limited to MECP2 mutation-positive children, one year - 9.99 years of age. This clinical trial, which is a placebo-controlled study, will randomize patients to the drug or placebo to determine the benefits of DM vs placebo on cognition, behavior, or seizures if present.
Your child will stay twice in the Pediatric Clinical Research Unit (PCRU) at Johns Hopkins ICTR, for 3 days during each admission. The first hospital stay will be for 3 days, before she starts the DM or placebo. The follow-up 3-day hospital stay will be 3 months after she starts taking DM or placebo. There will also be two interim follow up evaluations at 2 weeks and 1 month after she starts taking the DM or placebo consisting of a neurological evaluation, EKG, and blood work, which can take place at your local doctor's office or at Johns Hopkins, and will be paid for by this study. Our research nurse or research associate will contact you at least weekly during the first month, and at least monthly thereafter until the end of the 3-month study.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 1 Year 至 10 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •males and females who have classic or atypical RTT with a proven mutation in the MECP2 gene;
- •subjects must be between one year - 10 years of age.
排除标准
- •those without an established mutation in the MECP2 gene;
- •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. MAO inhibitors, SSRI, sibutramine etc. to avoid a serotonin syndrome; quinidine and drugs metabolized by the CYP450 isoform 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;
- •those showing poor compliance with any aspect of the study;
- •foster children.
研究组 & 干预措施
Study drug-dextromethorphan (DM)
MECP2 mutation positive subjects randomized to receive DM
干预措施: dextromethorphan (Drug)
Placebo group
MECP2 positive subjects randomized to the placebo compound
干预措施: placebo (Drug)
结局指标
主要结局
Change in Mullen; Visual Reception Sub-scale Scores, Pre- and Post-Intervention
时间窗: Initial evaluation and at the end of the 3 month trial
The Mullen Scales of Early Learning (MULLEN) Visual reception subscale raw scores range from Minimum=0 to Maximum=50. A higher score is a better outcome. Age equivalents from 1 month to 70 months can be computed for each subscale separately.
Change in Mullen; Fine Motor Sub-scale Scores, Pre- and Post-Intervention
时间窗: Baseline and 3 months
The Mullen Scales of Early Learning (MULLEN) Fine motor scale raw scores range from Minimum=0 to Maximum=49. A higher score is a better outcome. Age equivalents from 1 month to 70 months can be computed for each subscale separately.
Change in Mullen; Receptive Language Subscale Scores, Pre- and Post-Intervention
时间窗: Baseline and 3 months
The Mullen Scales of Early Learning (MULLEN) Receptive Language scale raw scores range from Minimum=0 to Maximum=50. A higher score is a better outcome. Age equivalents from 1 month to 70 months can be computed for each subscale separately.
Change in Mullen, Expressive Language Sub-scale Scores, Pre- and Post-Intervention
时间窗: Baseline and 3 months
The Mullen Scales of Early Learning (MULLEN) Expressive Language scale raw scores range from Minimum=0 to Maximum=50. A higher score is a better outcome. Age equivalents from 1 month to 70 months can be computed for each subscale separately.
次要结局
- Change in VABS: Motor Skills Domain Scores, Pre- and Post-Intervention(Baseline evaluation and at the end of the 3 month study)
- Change in VABS:Daily Living Skills Domain Scores, Pre- and Post-Intervention(Baseline and at the end of the 3 month trial)
- Change in VABS: Socialization Domain Scores, Pre- and Post-Intervention(Baseline and at the end of the 3 month trial)
- Change in VABS:Communication Domain Scores, Pre- and Post-Intervention(Baseline and at the end of the 3 month trial)
- Change in Ghuman-Folstein Screen for Social Interaction (SSI) Score, Pre- and Post-Intervention.(Initial evaluation and at the end of the 3 month study. The test lasts 45 minutes)
- Change in Rett Syndrome Behavior Questionnaire Score, Pre- and Post-Intervention(Initial evaluation and at the end of the 3 month study)
研究者
SakkuBai Naidu, M.D.
Professor of Neurology and Pediatrics
Hugo W. Moser Research Institute at Kennedy Krieger, Inc.