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Natural History of Rett Syndrome & Related Disorders

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02738281
Recruitment Status : Recruiting
First Posted : April 14, 2016
Last Update Posted : May 16, 2019
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Center for Advancing Translational Science (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)
Information provided by (Responsible Party):
Alan Percy, University of Alabama at Birmingham

Study Description
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Brief 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 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).

Condition or disease
Rett Syndrome MECP2 Duplication dIsorder CDKL5 Disorder FOXG1 Syndrome

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
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Study Type : Observational
Estimated Enrollment : 1200 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Rett Syndrome, MECP2 Duplication Disorder, and Rett- Related Disorders Natural History Protocol
Study Start Date : November 2015
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Rett Syndrome

Groups and Cohorts
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Group/Cohort
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.


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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

  14. 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........

  15. 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........


Secondary Outcome Measures :
  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
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)

Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • Individuals who do not meet the above criteria will be excluded.
Contacts and Locations
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Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02738281


Contacts
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Contact: Alan K Percy, MD 2059964927 apercy@uab.edu
Contact: Jane B Lane, RN, BSN 2059964927 jlane@uab.edu

Locations
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United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Jane Lane, RN, BSN    205-934-1130    jlane@uab.edu   
Principal Investigator: Alan Percy, MD         
United States, California
UCSF Benioff Children's Hospital of Oakland Recruiting
Oakland, California, United States, 94709
Contact: Erica Roberston    925-979-4055    ERobertson@mail.cho.org   
Principal Investigator: Mary Jones, MD         
Sub-Investigator: Audrey Brumback, MD, PhD         
University of California San Diego Recruiting
San Diego, California, United States, 92123
Contact: Karen Distlear, MS    858-246-2288    kditslear@ucsd.edu   
Principal Investigator: Richard Haas, MD         
United States, Colorado
University of Colorado Denver Recruiting
Denver, Colorado, United States, 80045-2571
Contact: Gina VanderVeen    720-777-5514    Gina.VanderVeen@childrenscolorado.org   
Principal Investigator: Tim Benke, MD, PhD         
United States, Illinois
Rush University Medical Center Recruiting
Chicago, Illinois, United States, 60612
Contact: Sausan Rohde    312-942-0079    susan_rohde@rush.edu   
Principal Investigator: Peter Heydemann, MD         
Sub-Investigator: Elizabeth Berry-Kravis, MD         
Sub-Investigator: Colleen Buhrfiend, MD         
United States, Massachusetts
Children's Hospital Boston Recruiting
Boston, Massachusetts, United States, 02115
Contact: Grace Bazin    617-355-5230    Grace.bazin@childrens.harvard.edu   
Contact: Lindsay Swanson, MS, CGS    617-355-5230    Lindsay.Swanson@childrens.harvard.edu   
Principal Investigator: Mustafa Sahin, MD, PhD         
United States, Minnesota
Gillette Children's Specialty Healthcare Recruiting
Saint Paul, Minnesota, United States, 55101
Contact: Rachel Kotoch, CCRC, BS    651-325-2331    rkatoch@gillettechildrens.com   
Principal Investigator: Arthir Beisang, MD         
United States, Missouri
Washington University School of Medicine and St. Louis Children's Hospital Recruiting
Saint Louis, Missouri, United States, 63110-1093
Contact: Olga Novak    314-454-4267    rettresearch@neuro.wustl.edu   
Principal Investigator: Robin Ryther, MD, PhD         
United States, New York
University of Rochester Recruiting
Rochester, New York, United States, 14627-0140
Contact: Alex Paciorkowski, MD, PhD    585-275-2808    alex_paciorkowski@urmc.rochester.edu   
Principal Investigator: Alex Paciorkowski, MD, PhD         
Sub-Investigator: Laurie Seltzer, MD         
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Max Mays    513-803-7935    Maxwell.mays@cchmc.org   
Principal Investigator: Shannon Standridge, DO         
Cleveland Clinic Not yet recruiting
Cleveland, Ohio, United States, 44195
Contact: Irys Caristo    216-444-0173    CARISTI@ccf.org   
Principal Investigator: Sumit Parikh, MD         
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104-4318
Contact: Casey Gorman    267-426-5171    GormanC@email.chop.edu   
Principal Investigator: Eric Marsh, MD, PhD         
United States, South Carolina
Greenwood Genetic Center Recruiting
Greenwood, South Carolina, United States, 29646
Contact: Fran Annese, LMSW    864-941-8100    fran@ggc.org   
Principal Investigator: Mike Friez, PhD         
Principal Investigator: Steve A Skinner, MD         
United States, Tennessee
Vanderbilt University Recruiting
Nashville, Tennessee, United States, 37212
Contact: Nicole Thompson    615-343-4586    Nicole.i.thompson@vanderbilt.edu   
Principal Investigator: Sar Peters, PhD         
Sub-Investigator: Cary Fu, MD         
United States, Texas
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Judy Barrish, BSN RN    832-822-7388    jobarris@texaschilrdens.org   
Principal Investigator: Daniel G Glaze, MD         
Sub-Investigator: Bernhard Suter, MD, PhD         
Sub-Investigator: Thuy Dinh, PA         
Sponsors and Collaborators
University of Alabama at Birmingham
National Institutes of Health (NIH)
National Center for Advancing Translational Science (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)
Investigators
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Principal Investigator: Alan K Percy, MD University of Alabama at Birmingham
Study Director: Jeffrey L Neul, MD, PhD Vanderbilt University
Study Director: Walter E Kaufmann, MD Greenwood Genetic Center
More Information
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Additional Information:
International Rett Syndrome Foundation website  This link exits the ClinicalTrials.gov site

Publications of Results:

Other Publications:
Neul, J.L. Rett Syndrome and MECP2-Related Disorders. in Autism Spectrum Disorders (eds. Amaral, D., Geschwind, D. & Dawson, G.) 776-800 (Oxford University Press, New York, 2011).

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Responsible Party: Alan Percy, Principal Investigator, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT02738281    
Other Study ID Numbers: RDCRN 5211
First Posted: April 14, 2016    Key Record Dates
Last Update Posted: May 16, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: This consortium will follow the RDCRN agreement to share data. This plan releases data five years after acquisition.
Additional relevant MeSH terms:
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Rett Syndrome
Disease
Syndrome
Pathologic Processes
Mental Retardation, X-Linked
Intellectual Disability
 Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System