Rett SyndromeNCT02738281
Natural History of Rett Syndrome & Related Disorders
An observational study of Rett Syndrome and MECP2 Duplication dIsorder, run by University of Alabama at Birmingham at 14 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Rett Syndrome, MECP2 Duplication dIsorder, CDKL5 Disorder
- How many people
- 1,044 participants
- Where
- 14 sitesUnited States
- Study dates
- Nov 2015to 31 Jul 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Females and males of all ages must have complete testing for MECP2, FOXG1 and CDKL5 genes mutations AND must meet these requirements: Gene positive for a sequence mutation, duplication or deletion in one of these 3 genes. OR Meet consensus criteria for Rett syndrome (typical or atypical)
Who may be able to join
- 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.
Who cannot join
- Individuals who do not meet the above criteria will be excluded.
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United States14 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Children's Hospital Boston
Boston, Massachusetts, 02115
Rush University Medical Center
Chicago, Illinois, 60612
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Cleveland Clinic
Cleveland, Ohio, 44195
University of Colorado Denver
Denver, Colorado, 80045-2571
Greenwood Genetic Center
Greenwood, South Carolina, 29646
Baylor College of Medicine
Houston, Texas, 77030
Vanderbilt University
Nashville, Tennessee, 37212
UCSF Oakland Benioff Children's Hospital
Oakland, California, 94709
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104-4318
Gillette Children's Specialty Healthcare
Saint Paul, Minnesota, 55101
University of California San Diego
San Diego, California, 92123
Washington University School of Medicine and St. Louis Children's Hospital
St Louis, Missouri, 63110-1093
About this study
Official title: Rett Syndrome, MECP2 Duplication Disorder, and Rett- Related Disorders Natural History Protocol
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).
Read the detailed description
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.
- Medical subject headings
- Rett Syndrome, CDKL5 deficiency disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Rett Syndrome | This is a prospective natural history study examining the phenotypic variations of individuals with mutations in MECP2 or meeting the diagnostic criteria for classic (typical) or variant (atypical) Rett syndrome. The overwhelming majority will be female, but males meeting diagnostic criteria will be included. No interventions are planned. | |
| MECP2 Duplication | This is a prospective natural history study examining the phenotypic variations of individuals with MECP2 duplications. The majority are expected to be males, but females expressing a duplication will be included. No interventions are planned. | |
| RTT related disorders | This is a prospective natural history study examining individuals, both females and males who do not meet criteria for Rett syndrome, but have a mutation in MECP2, CDKL5, or FOXG1. No interventions are planned. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical longitudinal assessments in Rett syndrome (RTT) as measured by mean growth over 5 years.
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.
Measured: at 5 years after enrollment
Clinical and neurobehavioral longitudinal assessments in Rett syndrome (RTT) as measured by mean change in head circumference over 5 years
the mean change in head circumference (measured in Centimeters) will be reported
Measured: at 5 years after enrollment
Clinical and neurobehavioral longitudinal assessments in Rett syndrome (RTT) as measured by mean number of stereotypic movements at 5 years
The mean number of stereotypic movements in a 24 hour period at 5 years.
Measured: at 5 years after enrollment
Clinical and neurobehavioral longitudinal assessments in Rett syndrome (RTT) as the percent of subjects with reported epilepsy at 5 years
The Percent of subjects reporting epilepsy by 5 years
Measured: 5 years after enrollment
Clinical and neurobehavioral longitudinal assessments in Rett syndrome (RTT) as the percent of subjects with reported scoliosis at 5 years
Percent of subjects with reported scoliosis
Measured: at 5 years after enrollment
Clinical and neurobehavioral longitudinal assessments in Rett syndrome (RTT) as the percent of subjects with MECP2 mutations at 5 years
% of subjects with MECP2 mutations to 5 years
Measured: at 5 years after enrollment
Clinical and neurobehavioral longitudinal assessments in Rett syndrome (RTT) as reported by the mean Clinical Severity Scale (CSS) at 5 years
The CSS is the clinical severity scale.
Measured: at 5 years after enrollment
Clinical and neurobehavioral longitudinal assessments in Rett syndrome (RTT) as measured by the mean Motor Behavioral Assessment (MBA) at 5 years
the MBA is the motor behavioral (performance) score
Measured: at 5 years after enrollment
Clinical and neurobehavioral longitudinal assessments in MECP2 duplication syndrome: mean growth rate over 5 years with subjects having MECP2 duplication syndrome
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.
Measured: at 5 years after enrollment
Clinical and neurobehavioral longitudinal assessments in MECP2 duplication syndrome: mean change in head circumference 5 years with subjects having MECP2 duplication syndrome
the mean change in head circumference (measured in Centimeters) will be reported
Measured: at 5 years after enrollment
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
The mean number of stereotypic movements in a 24 hour period at 5 years.
Measured: at 5 years after enrollment
Clinical and neurobehavioral longitudinal assessments in MECP2 duplication syndrome: percent of subjects reporting scoliosis 5 years with subjects having MECP2 duplication syndrome
Percent of subjects with reported scoliosis
Measured: at 5 years after enrollment
Clinical and neurobehavioral longitudinal assessments in MECP2 duplication syndrome: percent of subjects surviving at 5 years with subjects having MECP2 duplication syndrome
Percent of subjects surviving at 5 years after start of study
Measured: at 5 years after enrollment
Clinical and neurobehavioral longitudinal assessments in MECP2 duplication syndrome: the mean CSS score at 5 years with subjects having MECP2 duplication syndrome
the CSS........
Measured: at 5 years after enrollment
Clinical and neurobehavioral longitudinal assessments in MECP2 duplication syndrome: the mean MAB score at 5 years with subjects having MECP2 duplication syndrome
the MBA........
Measured: at 5 years after enrollment
Secondary outcomes (6)
Quality of Life Measures in RTT
Summative data are provided by the quality of life assessments for children (CHQ), the mean score will.be reported
Measured: at 5 years post enrollment
Quality of Life Measures in MECP2 duplication syndrome
Summative data are provided by the quality of life assessments for children (CHQ), the mean scores will be reported.
Measured: at 5 years post enrollment
Quality of Life Measures in RTT-related disorders.
Summative data are provided by the quality of life assessments for children (CHQ), the mean score will be reported.
Measured: at 5 years post enrollment
Quality of Life Measures in RTT
Summative data are provided by the quality of life assessments from the principal caregiver (SF-36), the mean score will be reported.
Measured: at 5 years post enrollment
Quality of Life Measures in MECP2 duplication syndrome
Summative data are provided by the quality of life assessments from the principal caregiver (SF-36), the mean score will be reported.
Measured: at 5 years post enrollment
Quality of Life Measures in RTT-related disorders
Summative data are provided by the quality of life assessments from the principal caregiver (SF-36), the mean score will be reported.
Measured: at 5 years post enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2016 (estimated)
- Study startNov 2015
- Primary completion31 Jul 2021
- Study completion31 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (76)Papers the sponsor has linked to this study.
- Other trials for Rett SyndromeStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,044 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Center for Advancing Translational Sciences (NCATS), Rare Diseases Clinical Research Network, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Principal investigator, Alan Percy, University of Alabama at Birmingham
- Investigators
- Alan K Percy, MD, Principal investigator, University of Alabama at BirminghamJeffrey L Neul, MD, PhD, Study director, Vanderbilt University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02738281
- Sponsor's protocol ID
- RDCRN 5211
- Status last verified
- Aug 2021
- First submitted
- 22 Nov 2015
- Last updated
- 5 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: This consortium will follow the RDCRN agreement to share data. This plan releases data five years after acquisition.
Publications
Hagberg B, Aicardi J, Dias K, Ramos O. A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett's syndrome: report of 35 cases. Ann Neurol. 1983 Oct;14(4):471-9. doi: 10.1002/ana.410140412.
PubMed 6638958Neul JL, Kaufmann WE, Glaze DG, Christodoulou J, Clarke AJ, Bahi-Buisson N, Leonard H, Bailey ME, Schanen NC, Zappella M, Renieri A, Huppke P, Percy AK; RettSearch Consortium. Rett syndrome: revised diagnostic criteria and nomenclature. Ann Neurol. 2010 Dec;68(6):944-50. doi: 10.1002/ana.22124.
PubMed 21154482Nan X, Bird A. The biological functions of the methyl-CpG-binding protein MeCP2 and its implication in Rett syndrome. Brain Dev. 2001 Dec;23 Suppl 1:S32-7. doi: 10.1016/s0387-7604(01)00333-3.
PubMed 11738839Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet. 1999 Oct;23(2):185-8. doi: 10.1038/13810.
PubMed 10508514Wan M, Lee SS, Zhang X, Houwink-Manville I, Song HR, Amir RE, Budden S, Naidu S, Pereira JL, Lo IF, Zoghbi HY, Schanen NC, Francke U. Rett syndrome and beyond: recurrent spontaneous and familial MECP2 mutations at CpG hotspots. Am J Hum Genet. 1999 Dec;65(6):1520-9. doi: 10.1086/302690.
PubMed 10577905Suter B, Treadwell-Deering D, Zoghbi HY, Glaze DG, Neul JL. Brief report: MECP2 mutations in people without Rett syndrome. J Autism Dev Disord. 2014 Mar;44(3):703-11. doi: 10.1007/s10803-013-1902-z.
PubMed 23921973Laurvick CL, de Klerk N, Bower C, Christodoulou J, Ravine D, Ellaway C, Williamson S, Leonard H. Rett syndrome in Australia: a review of the epidemiology. J Pediatr. 2006 Mar;148(3):347-52. doi: 10.1016/j.jpeds.2005.10.037.
PubMed 16615965Kerr AM, Armstrong DD, Prescott RJ, Doyle D, Kearney DL. Rett syndrome: analysis of deaths in the British survey. Eur Child Adolesc Psychiatry. 1997;6 Suppl 1:71-4.
PubMed 9452925Guy J, Gan J, Selfridge J, Cobb S, Bird A. Reversal of neurological defects in a mouse model of Rett syndrome. Science. 2007 Feb 23;315(5815):1143-7. doi: 10.1126/science.1138389. Epub 2007 Feb 8.
PubMed 17289941Garg SK, Lioy DT, Cheval H, McGann JC, Bissonnette JM, Murtha MJ, Foust KD, Kaspar BK, Bird A, Mandel G. Systemic delivery of MeCP2 rescues behavioral and cellular deficits in female mouse models of Rett syndrome. J Neurosci. 2013 Aug 21;33(34):13612-20. doi: 10.1523/JNEUROSCI.1854-13.2013.
PubMed 23966684Chang Q, Khare G, Dani V, Nelson S, Jaenisch R. The disease progression of Mecp2 mutant mice is affected by the level of BDNF expression. Neuron. 2006 Feb 2;49(3):341-8. doi: 10.1016/j.neuron.2005.12.027.
PubMed 16446138Tropea D, Giacometti E, Wilson NR, Beard C, McCurry C, Fu DD, Flannery R, Jaenisch R, Sur M. Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice. Proc Natl Acad Sci U S A. 2009 Feb 10;106(6):2029-34. doi: 10.1073/pnas.0812394106.
PubMed 19208815Archer H, Evans J, Leonard H, Colvin L, Ravine D, Christodoulou J, Williamson S, Charman T, Bailey ME, Sampson J, de Klerk N, Clarke A. Correlation between clinical severity in patients with Rett syndrome with a p.R168X or p.T158M MECP2 mutation, and the direction and degree of skewing of X-chromosome inactivation. J Med Genet. 2007 Feb;44(2):148-52. doi: 10.1136/jmg.2006.045260. Epub 2006 Aug 11.
PubMed 16905679Leonard H, Bower C. Is the girl with Rett syndrome normal at birth? Dev Med Child Neurol. 1998 Feb;40(2):115-21.
PubMed 9489500Kerr AM. Early clinical signs in the Rett disorder. Neuropediatrics. 1995 Apr;26(2):67-71. doi: 10.1055/s-2007-979725.
PubMed 7566455
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rett Syndrome, MECP2 Duplication Disorder, and Rett- Related Disorders Natural History Protocol
- ClinicalTrials.gov ID
- NCT02738281
- Acronym / sponsor ID
- RDCRN 5211
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,044 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Center for Advancing Translational Sciences (NCATS), Rare Diseases Clinical Research Network, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Nov 2015
- Primary completion
- 31 Jul 2021 (actual)
- Study completion
- 31 Jul 2021 (actual)
- First posted
- 14 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Rett Syndrome | – | –This is a prospective natural history study examining the phenotypic variations of individuals with mutations in MECP2 or meeting the diagnostic criteria for classic (typical) or variant (atypical) Rett syndrome. The overwhelming majority will be female, but males meeting diagnostic criteria will be included. No interventions are planned. |
| MECP2 Duplication | – | –This is a prospective natural history study examining the phenotypic variations of individuals with MECP2 duplications. The majority are expected to be males, but females expressing a duplication will be included. No interventions are planned. |
| RTT related disorders | – | –This is a prospective natural history study examining individuals, both females and males who do not meet criteria for Rett syndrome, but have a mutation in MECP2, CDKL5, or FOXG1. No interventions are planned. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Females and males of all ages must have complete testing for MECP2, FOXG1 and CDKL5 genes mutations AND must meet these requirements: Gene positive for a sequence mutation, duplication or deletion in one of these 3 genes. OR Meet consensus criteria for Rett syndrome (typical or atypical)
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- Individuals who do not meet the above criteria will be excluded.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
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 years
Time frame: 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
Time frame: at 5 years after enrollment
The CSS is the clinical severity scale.
Clinical and neurobehavioral longitudinal assessments in Rett syndrome (RTT) as measured by the mean Motor Behavioral Assessment (MBA) at 5 years
Time frame: at 5 years after enrollment
the MBA is the motor behavioral (performance) score
Clinical and neurobehavioral longitudinal assessments in MECP2 duplication syndrome: mean growth rate over 5 years with subjects having MECP2 duplication syndrome
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 MECP2 duplication syndrome: mean change in head circumference 5 years with subjects having MECP2 duplication syndrome
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 MECP2 duplication syndrome: mean number of stereotypic movements in a 24 hour period at 5 years with subjects having MECP2 duplication syndrome
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 MECP2 duplication syndrome: percent of subjects reporting scoliosis 5 years with subjects having MECP2 duplication syndrome
Time frame: at 5 years after enrollment
Percent of subjects with reported scoliosis
Clinical and neurobehavioral longitudinal assessments in MECP2 duplication syndrome: percent of subjects surviving at 5 years with subjects having MECP2 duplication syndrome
Time frame: 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
Time frame: at 5 years after enrollment
the CSS........
Clinical and neurobehavioral longitudinal assessments in MECP2 duplication syndrome: the mean MAB score at 5 years with subjects having MECP2 duplication syndrome
Time frame: at 5 years after enrollment
the MBA........
6 secondary outcomes
Quality of Life Measures in RTT
Time frame: at 5 years post enrollment
Quality of Life Measures in MECP2 duplication syndrome
Time frame: at 5 years post enrollment
Quality of Life Measures in RTT-related disorders.
Time frame: at 5 years post enrollment
Quality of Life Measures in RTT
Time frame: at 5 years post enrollment
Quality of Life Measures in MECP2 duplication syndrome
Time frame: at 5 years post enrollment
Quality of Life Measures in RTT-related disorders
Time frame: at 5 years post enrollment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2021.
- Background: PubMed 6638958Hagberg B, Aicardi J, Dias K, Ramos O. A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett's syndrome: report of 35 cases. Ann Neurol. 1983 Oct;14(4):471-9. doi: 10.1002/ana.410140412.
- Background: PubMed 21154482Neul JL, Kaufmann WE, Glaze DG, Christodoulou J, Clarke AJ, Bahi-Buisson N, Leonard H, Bailey ME, Schanen NC, Zappella M, Renieri A, Huppke P, Percy AK; RettSearch Consortium. Rett syndrome: revised diagnostic criteria and nomenclature. Ann Neurol. 2010 Dec;68(6):944-50. doi: 10.1002/ana.22124.
- Background: PubMed 11738839Nan X, Bird A. The biological functions of the methyl-CpG-binding protein MeCP2 and its implication in Rett syndrome. Brain Dev. 2001 Dec;23 Suppl 1:S32-7. doi: 10.1016/s0387-7604(01)00333-3.
- Background: PubMed 10508514Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet. 1999 Oct;23(2):185-8. doi: 10.1038/13810.
- Background: PubMed 10577905Wan M, Lee SS, Zhang X, Houwink-Manville I, Song HR, Amir RE, Budden S, Naidu S, Pereira JL, Lo IF, Zoghbi HY, Schanen NC, Francke U. Rett syndrome and beyond: recurrent spontaneous and familial MECP2 mutations at CpG hotspots. Am J Hum Genet. 1999 Dec;65(6):1520-9. doi: 10.1086/302690.
- Background: PubMed 23921973Suter B, Treadwell-Deering D, Zoghbi HY, Glaze DG, Neul JL. Brief report: MECP2 mutations in people without Rett syndrome. J Autism Dev Disord. 2014 Mar;44(3):703-11. doi: 10.1007/s10803-013-1902-z.
- Background: PubMed 16615965Laurvick CL, de Klerk N, Bower C, Christodoulou J, Ravine D, Ellaway C, Williamson S, Leonard H. Rett syndrome in Australia: a review of the epidemiology. J Pediatr. 2006 Mar;148(3):347-52. doi: 10.1016/j.jpeds.2005.10.037.
- Background: PubMed 9452925Kerr AM, Armstrong DD, Prescott RJ, Doyle D, Kearney DL. Rett syndrome: analysis of deaths in the British survey. Eur Child Adolesc Psychiatry. 1997;6 Suppl 1:71-4.
- Background: PubMed 17289941Guy J, Gan J, Selfridge J, Cobb S, Bird A. Reversal of neurological defects in a mouse model of Rett syndrome. Science. 2007 Feb 23;315(5815):1143-7. doi: 10.1126/science.1138389. Epub 2007 Feb 8.
- Background: PubMed 23966684Garg SK, Lioy DT, Cheval H, McGann JC, Bissonnette JM, Murtha MJ, Foust KD, Kaspar BK, Bird A, Mandel G. Systemic delivery of MeCP2 rescues behavioral and cellular deficits in female mouse models of Rett syndrome. J Neurosci. 2013 Aug 21;33(34):13612-20. doi: 10.1523/JNEUROSCI.1854-13.2013.
- Background: PubMed 16446138Chang Q, Khare G, Dani V, Nelson S, Jaenisch R. The disease progression of Mecp2 mutant mice is affected by the level of BDNF expression. Neuron. 2006 Feb 2;49(3):341-8. doi: 10.1016/j.neuron.2005.12.027.
- Background: PubMed 19208815Tropea D, Giacometti E, Wilson NR, Beard C, McCurry C, Fu DD, Flannery R, Jaenisch R, Sur M. Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice. Proc Natl Acad Sci U S A. 2009 Feb 10;106(6):2029-34. doi: 10.1073/pnas.0812394106.
- International Rett Syndrome Foundation websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. This consortium will follow the RDCRN agreement to share data. This plan releases data five years after acquisition.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alan K Percy, MD principal investigator
University of Alabama at Birmingham
Jeffrey L Neul, MD, PhD study director
Vanderbilt University
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Rett Syndrome and MECP2 Duplication dIsorder, run by University of Alabama at Birmingham at 14 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical longitudinal assessments in Rett syndrome (RTT) as measured by mean growth over 5 years. (time frame: at 5 years after enrollment). The study lists 15 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02738281, which also lists 76 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2021.