Clinical Trial: Natural History of Rett Syndrome & Related Disorders
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational
Official Title: Rett Syndrome, MECP2 Duplication Disorder, and Rett- Related Disorders Natural History Protocol
Brief Summary: The purpose of this study is to advance understanding of the natural history of Rett syndrome (RTT), MECP2-duplication disorder (MECP2 Dup), RTT-related disorders including 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).
Detailed Summary: 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 clinic
Sponsor: University of Alabama at Birmingham
Current Primary Outcome:
- Clinical longitudinal assessments in Rett syndrome (RTT) as measured by mean growth over 5 years. [ Time Frame: 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 measured by mean change in head circumference over 5 years [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 5 years after enrollment ]The Percent of subjects reporting epilepsy by 5 years
- Clinical and neurobehavioral longitudinal assessments in Rett syndrome (RTT) as the percent of subjects with reported scoliosis at 5 years [ Time Frame: at 5 years after enrollment ]Percent of subjects with reported scoliosis
- Clinical and neurobehavioral longitudinal assessments in Rett syndrome (RTT) as the percent of subjects with MECP2 mutations at 5 yea
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Quality of Life Measures in RTT [ Time Frame: at 5 years post enrollment ]Summative data are provided by the quality of life assessments for children (CHQ), the mean score will.be reported
- Quality of Life Measures in MECP2 duplication syndrome [ Time Frame: at 5 years post enrollment ]Summative data are provided by the quality of life assessments for children (CHQ), the mean scores will be reported.
- Quality of Life Measures in RTT-related disorders. [ Time Frame: at 5 years post enrollment ]Summative data are provided by the quality of life assessments for children (CHQ), the mean score will be reported.
- Quality of Life Measures in RTT [ Time Frame: at 5 years post enrollment ]Summative data are provided by the quality of life assessments from the principal caregiver (SF-36), the mean score will be reported.
- Quality of Life Measures in MECP2 duplication syndrome [ Time Frame: at 5 years post enrollment ]Summative data are provided by the quality of life assessments from the principal caregiver (SF-36), the mean score will be reported.
- Quality of Life Measures in RTT-related disorders [ Time Frame: at 5 years post enrollment ]Summative data are provided by the quality of life assessments from the principal caregiver (SF-36), the mean score will be reported.
Original Secondary Outcome:
- Quality of Life Measures in RTT [ Time Frame: at 5 years post enrollment ]Summative data are provided by the quality of life assessments for children (CHQ) and the principal caregiver (SF-36).
- Quality of Life Measures in MECP2 duplication syndrome [ Time Frame: at 5 years post enrollment ]Summative data are provided by the quality of life assessments for children (CHQ) and the principal caregiver (SF-36).
- Mean Quality of Life Measures in RTT-related disorders: mean score of Childrens Health Questionnaire [ Time Frame: at 5 years post enrollment ]Summative data are provided by the quality of life assessments for children (CHQ) the mean score will be reported
- Mean Quality of Life Measures in RTT-related disorders: care giver mean score (SF-36 [ Time Frame: at 5 years post enrollment ]Summative data are provided by the quality of life assessments from the principal caregiver (SF-36). the mean score will be reported
Information By: University of Alabama at Birmingham
Dates:
Date Received: November 22, 2015
Date Started: November 2015
Date Completion: December 2019
Last Updated: May 18, 2017
Last Verified: May 2017
- Quality of Life Measures in RTT [ Time Frame: at 5 years post enrollment ]
