Rett Syndrome, MECP2 Duplication Disorder, and Rett- Related Disorders Natural History Protocol
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 1,044
- 试验地点
- 14
- 主要终点
- Clinical and neurobehavioral longitudinal assessments in Rett syndrome (RTT) as the percent of subjects with MECP2 mutations at 5 years
研究概览
简要总结
The purpose of this study is to advance understanding of the natural history of Rett syndrome (RTT), MECP2-duplication disorder (MECP2 Dup), CDKL5, FOXG1, and individuals with MECP2 mutations who do not have RTT including the range of clinical involvement and to correlate genotype-phenotype over a broad spectrum of phenotypes. While much has been learned about RTT, improvements are required in understanding the role of factors such as X chromosome inactivation, genetic background, and others including the environment, on the great variability observed even between individuals with the same MECP2 mutation. These data will be essential to the development and conduct of clinical trials that are anticipated from ongoing studies in animal models for RTT. This study will not include clinical trials, but should set the stage for such trials and other translational research projects (e.g., development of biomarkers).
详细描述
At the present time, effective treatments for RTT, MECP2 Dup, or Rett-related disorders are lacking. Substantial progress has been made in RTT over the past eleven years such that this study represents a narrowing of focus to mutations or duplications of the MECP2 gene and related disorders, including those with phenotypic overlap. Understanding of RTT has advanced remarkably well through the Rett Syndrome Natural History Clinical Protocol (NHS) and correspondingly advancement in the basic science realm has moved forward with equivalent success. Thus, progress in clinical and basic science has led to the establishment of clinical trials and other translational studies that hold promise for additional clinical trials in future. In the process, however, additional MECP2- and RTT-related disorders that were unknown at the time the original proposal have been identified. In addition, substantial clinical variability in individuals with RTT that cannot be explained by differences in mutations alone must be explored further. In fact, variability among individuals with identical mutations has led to the search for additional explanations. At the time of the initial application (2002), just three years after the identification of the gene, MECP2, as the molecular link to RTT, the variation in clinical disorders related to MECP2 mutations or to the related but quite different MECP2 Dup were unknown. Each disorder is characterized by significant neurodevelopmental features related either to alterations in the MECP2 gene or related to phenotypes closely resembling those seen in individuals with RTT. Further, the phenotypic overlap with RTT due to mutations in CDKL5 and FOXG1 was also unexplored. This new study will build on the substantial progress made in understanding both classic and variant RTT and to add these related disorders, MECP2 Dup and the Rett-related disorders including CDKL5, FOXG1, and individuals with MECP2 mutations who do not have RTT. A comprehensive clinical research program will be performed including clinical, neurophysiologic, and molecular and biochemical markers across these different, but related disorders. This protocol will address the natural history components only and will serve as the basis for other study protocols including the neurophysiologic and biomarker studies. Thereby, these studies will represent a continuing pathway to focus and inform not only the ongoing but also the emerging clinical trials.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Individuals of both genders and of all ages, with RTT, MECP2 Dup, and, RTT-related disorders including those with mutations or deletions in CDKL5 and FOXG1 genes, or those with RTT (atypical or typical) who are mutation negative.
排除标准
- •Individuals who do not meet the above criteria will be excluded.
结局指标
主要结局
Clinical and neurobehavioral longitudinal assessments in Rett syndrome (RTT) as the percent of subjects with MECP2 mutations at 5 years
时间窗: at 5 years after enrollment
% of subjects with MECP2 mutations to 5 years
Clinical and neurobehavioral longitudinal assessments in Rett syndrome (RTT) as reported by the mean Clinical Severity Scale (CSS) at 5 years
时间窗: at 5 years after enrollment
The CSS is the clinical severity scale.
Clinical and neurobehavioral longitudinal assessments in Rett syndrome (RTT) as measured by mean change in head circumference over 5 years
时间窗: at 5 years after enrollment
the mean change in head circumference (measured in Centimeters) will be reported
Clinical and neurobehavioral longitudinal assessments in Rett syndrome (RTT) as measured by mean number of stereotypic movements at 5 years
时间窗: at 5 years after enrollment
The mean number of stereotypic movements in a 24 hour period at 5 years.
Clinical and neurobehavioral longitudinal assessments in Rett syndrome (RTT) as the percent of subjects with reported epilepsy at 5 years
时间窗: 5 years after enrollment
The Percent of subjects reporting epilepsy by 5 years
Clinical longitudinal assessments in Rett syndrome (RTT) as measured by mean growth over 5 years.
时间窗: at 5 years after enrollment
subject's height will be measured in inches at baseline and at 5 years. The change will be calculated and then the mean change will be reported.
Clinical and neurobehavioral longitudinal assessments in MECP2 duplication syndrome: mean growth rate over 5 years with subjects having MECP2 duplication syndrome
时间窗: at 5 years after enrollment
subject's height will be measured in inches at baseline and at 5 years. The change will be calculated and then the mean change will be reported.
Clinical and neurobehavioral longitudinal assessments in Rett syndrome (RTT) as the percent of subjects with reported scoliosis at 5 years
时间窗: at 5 years after enrollment
Percent of subjects with reported scoliosis
Clinical and neurobehavioral longitudinal assessments in Rett syndrome (RTT) as measured by the mean Motor Behavioral Assessment (MBA) at 5 years
时间窗: at 5 years after enrollment
the MBA is the motor behavioral (performance) score
Clinical and neurobehavioral longitudinal assessments in MECP2 duplication syndrome: mean number of stereotypic movements in a 24 hour period at 5 years with subjects having MECP2 duplication syndrome
时间窗: at 5 years after enrollment
The mean number of stereotypic movements in a 24 hour period at 5 years.
Clinical and neurobehavioral longitudinal assessments in MECP2 duplication syndrome: percent of subjects surviving at 5 years with subjects having MECP2 duplication syndrome
时间窗: at 5 years after enrollment
Percent of subjects surviving at 5 years after start of study
Clinical and neurobehavioral longitudinal assessments in MECP2 duplication syndrome: the mean CSS score at 5 years with subjects having MECP2 duplication syndrome
时间窗: at 5 years after enrollment
the CSS........
Clinical and neurobehavioral longitudinal assessments in MECP2 duplication syndrome: mean change in head circumference 5 years with subjects having MECP2 duplication syndrome
时间窗: at 5 years after enrollment
the mean change in head circumference (measured in Centimeters) will be reported
Clinical and neurobehavioral longitudinal assessments in MECP2 duplication syndrome: the mean MAB score at 5 years with subjects having MECP2 duplication syndrome
时间窗: at 5 years after enrollment
the MBA........
Clinical and neurobehavioral longitudinal assessments in MECP2 duplication syndrome: percent of subjects reporting scoliosis 5 years with subjects having MECP2 duplication syndrome
时间窗: at 5 years after enrollment
Percent of subjects with reported scoliosis
次要结局
- Quality of Life Measures in RTT(at 5 years post enrollment)
- Quality of Life Measures in RTT-related disorders(at 5 years post enrollment)
- Quality of Life Measures in MECP2 duplication syndrome(at 5 years post enrollment)
- Quality of Life Measures in RTT-related disorders.(at 5 years post enrollment)
研究者
Alan Percy
Principal Investigator
University of Alabama at Birmingham