Rett SyndromeNCT03196323
Development of a Behavioral Outcome Measure for Rett Syndrome (RettBe)
An observational study of Rett Syndrome, run by University of South Florida at 1 site in United States.
Trial summary
The overall purpose of this study is to develop a broad-based (i.e., multiple domains) behavioral outcome measure for children between the ages of 3-18 years with Rett syndrome (RTT). Read more about this study
- Who is it for?
- Ages 3 to 18 years, women only
- Conditions the study is for
- Rett Syndrome
- How many people
- 146 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2017to 24 Sep 2020
- 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 3 to 18 years
- Women only
- Child, Adult
Study population: A total of 400 subjects with RTT between the ages of 3 and 18 years of age will be recruited from RTT5211, which collects longitudinal clinical and neurobehavioral data in RTT and related disorders. This study will only include participants who meet 2010 diagnostic criteria for classic or atypical RTT and have a MECP2 mutation. Recruitment into this study will come from the larger cohort of those enrolled in the Natural History Study (RTT5211), a study aiming at enrolling 1000 participants with RTT. As a part of the Natural History Study (RTT5211), subjects provide their email address. RTT5211 participants will be emailed an invitation to join this study. Consent and study participation will be done online via a unique link in the invitation.
Who may be able to join
- RettBe 1.0 Initial Cohort:
- Females 3 - 18 years
- Meets revised 2010 diagnostic criteria for classic or atypical RTT
- Post-regression status
- Documentation of positive MECP2 mutation
- Enrolled in the Natural History Study (RTT5211)
Show all 10Show fewer
- RettBe 2.0 Validation Cohort:
- Meet above criteria
- Two raters are available and willing to evaluate the subject
- Must not have participated in RettBe 1.0
Who cannot join
- Both RettBe 1.0 and RettBe 2.0:
- Do not meet the above inclusion criteria
- Foster children
- Non-English speakers
Trial locations and contacts
1 site in 1 country.
About this study
The overall purpose of this study is to develop a broad-based (i.e., multiple domains) behavioral outcome measure for children between the ages of 3-18 years with Rett syndrome (RTT). The innovative approach of this proposal consists of integrating the process of developing a behavioral questionnaire to an ongoing large-scale data collection project. The Natural History Study of Rett Syndrome and Related Disorders (RTT5211) is a project that collects data on diverse aspects of the clinical evolution of individuals with RTT and related disorders. This project will serve as the basis for recruitment of subjects and it will also provide key demographic and clinical data for cohort characterization and for determining clinical relevance of the instrument (RettBe). An initial 100-subject cohort will allow for the testing with one rater of RettBe 1.0, a 50-item questionnaire formed from existing measures, a panel of clinicians and behavioral experts in RTT, and a focus group of parents and caregivers of children with RTT. Scores on RettBe 1.0 will be statistically analyzed to determine their psychometric properties, including its content validity. Items that do not meet psychometric standards (e.g., ceiling effect) will be eliminated.
Additional items will be added if the parental survey attached to RettBe 1.0 or clinician input suggests so. The resulting modified assessment, called RettBe 2.0, will be administered to a larger (validation) cohort of 300 participants. RettBe 2.0 will also be subjected to analysis of psychometric properties. RettBe 2.0 will also be administered to two raters per subject, in order to determine inter-rater reliability. In addition, these raters will be completing other behavioral and clinical measures for further evaluating the validity of RettBe 2.0 as well as for determining its clinical and functional significance. Finally, the investigators will obtain input from a panel of clinicians (site PIs and their designated clinicians) about content validity and clinical impact. The resulting version will be released as RettBe 3.0.
Read the detailed description
Behavioral abnormalities, ranging from autistic symptoms to anxiety and mood lability, are now recognized as major clinical issues in RTT. These clinical manifestations are particularly problematic in higher functioning individuals since they seem to substantially affect their quality of life. Moreover, novel drug treatments aiming at RTT's neurobiological mechanisms have the potential of targeting these abnormal behaviors. Despite the recent emphasis on abnormal behaviors, little is known about their characteristics, severity, and impact. This is due, in part, to the paucity of behavioral measures compatible with the cognitive and motor impairments of RTT. The investigators currently have only one instrument with limited validation for delineating the range of behavioral abnormalities in RTT (the parent-rated Rett Syndrome Behavioral Questionnaire (RSBQ)), which is a significant shortcoming to the implementation of treatment trials. Moreover, there has not been a systematic approach for defining behavioral abnormalities in RTT (e.g., definition of mood abnormalities in RTT). These deficiencies have led the investigators to propose the creation of a broad-based behavioral outcome measure for use in RTT at different ages. Due to the complexity of the clinical evolution of RTT and the relative limited knowledge on its adult period, the investigators will focus on children with RTT ages 3-18 years. The new measure will allow for standardized quantifications of behavioral outcomes in treatment trials and, eventually, in clinical practice. The investigators recognize that developing an instrument with strong psychometric properties is a major endeavor; therefore, the investigators conceived this project as a multi-stage process.
The first stage, conducted with support of Rettsyndrome.org, consisted of developing a prototype or first version of a behavioral questionnaire for parents of children with RTT (3-18 years), which the investigators have termed RettBe 1.0. The initial part of this study will test the psychometric properties (i.e., structure, content validity) of RettBe 1.0 with an initial cohort of 100 participants. This stage intends to transform RettBe 1.0 into a fully developed behavioral instrument within the framework of the Natural History Study (RTT5211). Thus, in Aim 1 the investigators will evaluate psychometrically RettBe 1.0 following, in part, previous studies including their examination of anxiety instruments and adaptation of the Anxiety, Depression and Mood Scale (ADAMS) for RTT, and their adaptations of the Aberrant Behavior Checklist-Community (ABC-C) for fragile X syndrome and Down syndrome. In Aim 1, they will also refine RettBe 1.0 by adding new "missing" items based on parental input or clinician (PIs of sites involved) feedback. The resulting instrument, RettBe 2.0 will be tested in Aim 2.
Testing of RettBe 2.0 will be carried out with a new (naïve) validation cohort of 300 subjects and two raters (preferentially both parents/caregivers, alternatively one teacher or therapist), to determine inter-rater reliability. One rater, preferentially a parent, will be asked to also complete three other behavioral measures (RSBQ, ADAMS, ABC-C) for comparisons. Scores for RettBe 2.0 will be analyzed in terms of psychometric properties, as performed for RettBe 1.0. However, in addition to structure (construct validity) and content validity, the investigators will also examine convergent and discriminant validity by correlating domain RettBe 2.0 scores with those of comparable and non-comparable domain scores of the RSBQ, ADAMS, and ABC-C, respectively.
Finally, Aim 3 will use data from the RTT5211 protocol to determine the effect of age on RettBe 2.0 scores and the clinical and functional significance of the measure. Specifically, the investigators will examine score distributions throughout the age range, with special emphasis on early childhood (3-8 years), late childhood (8-12 years), and adolescence (>12 years). Clinical and functional relevance will be determined by correlations with instruments measuring multiple parameters of clinical severity, specifically, the CGI-S, Clinical Severity Scale, and Motor Behavior Assessment. Relevance to quality of life will be evaluated by correlations with the Child Health Questionnaire-Parent Form 50 (CHQ-PF50; child-oriented measure) and The Short Form (36) Health Survey (SF-36v2TM Health Survey; parent-oriented measure). All these instruments are components of the core RTT5211 protocol. Finally, prior to its release as RettBe 3.0 (if psychometric properties are good-excellent), the investigators will obtain input from a panel of clinicians (site PIs and their designated clinicians) about content validity and clinical impact.
- Conditions
- Rett Syndrome
- Medical subject headings
- Rett Syndrome
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 |
|---|---|---|
| Initial Cohort | In Aim 1, the investigators will evaluate psychometrically RettBe 1.0 following, in part, previous studies including our examination of anxiety instruments and adaptation of the Anxiety, Depression and Mood Scale (ADAMS) for RTT, and their adaptations of the Aberrant Behavior Checklist-Community (ABC-C) for fragile X syndrome and Down syndrome. In Aim 1, the investigators will also refine RettBe 1.0 by adding new "missing" items based on parental input or clinician (PIs of sites involved) feedback. The resulting instrument, RettBe 2.0 will be tested in Aim 2. | |
| Validation Cohort | Testing of RettBe 2.0 will be carried out with a new (naïve) validation cohort of 300 subjects and two raters (preferentially both parents/caregivers, alternatively one teacher or therapist), to determine inter-rater reliability. One rater, preferentially a parent, will be asked to also complete three other behavioral measures (RSBQ, ADAMS, ABC-C) for comparisons. Scores for RettBe 2.0 will be analyzed in terms of psychometric properties, as performed for RettBe 1.0. However, in addition to structure (construct validity) and content validity, the investigators will also examine convergent and discriminant validity by correlating domain RettBe 2.0 scores with those of comparable and non-comparable domain scores of the RSBQ, ADAMS, and ABC-C, respectively. |
What is being measured
The primary outcome is the main question the study is designed to answer.
RettBE 1.0 Score
Scores from RettBe 1.0, a 50-item questionnaire will be analyzed for psychometric properties, including content validity. RettBe 1.0 scores will be subjected to factor analysis to ensure domain-appropriate balance and structure.
Measured: 8 months
RettBe 2.0 Score
RettBe 2.0 will be analyzed for psychometric properties. In addition, these raters will be completing other behavioral and clinical/functional measures for further evaluating the validity of RettBe 2.0 as well as for determining its clinical and functional significance (Aim 3). RettBe 2.0 will be subjected to factor analysis to ensure domain-appropriate balance and structure.
Measured: 8 months
RettBe 3.0 Score
RettBe 3.0 scores will be subjected to factor analysis to ensure domain-appropriate balance and structure.
Measured: 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2017
- Study start1 Jun 2017
- Primary completion24 Sep 2020
- Study completion24 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)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 South FloridaThe 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
- 146 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of South Florida
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Center for Advancing Translational Sciences (NCATS), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03196323
- Sponsor's protocol ID
- RTT5214
- Status last verified
- Dec 2020
- First submitted
- 2 Jun 2017
- Last updated
- 9 Dec 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Neul 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 21154482Robertson L, Hall SE, Jacoby P, Ellaway C, de Klerk N, Leonard H. The association between behavior and genotype in Rett syndrome using the Australian Rett Syndrome Database. Am J Med Genet B Neuropsychiatr Genet. 2006 Mar 5;141B(2):177-83. doi: 10.1002/ajmg.b.30270.
PubMed 16389588Lane JB, Lee HS, Smith LW, Cheng P, Percy AK, Glaze DG, Neul JL, Motil KJ, Barrish JO, Skinner SA, Annese F, McNair L, Graham J, Khwaja O, Barnes K, Krischer JP. Clinical severity and quality of life in children and adolescents with Rett syndrome. Neurology. 2011 Nov 15;77(20):1812-8. doi: 10.1212/WNL.0b013e3182377dd2. Epub 2011 Oct 19.
PubMed 22013176Cobb S, Guy J, Bird A. Reversibility of functional deficits in experimental models of Rett syndrome. Biochem Soc Trans. 2010 Apr;38(2):498-506. doi: 10.1042/BST0380498.
PubMed 20298210Kaufmann WE, Tierney E, Rohde CA, Suarez-Pedraza MC, Clarke MA, Salorio CF, Bibat G, Bukelis I, Naram D, Lanham DC, Naidu S. Social impairments in Rett syndrome: characteristics and relationship with clinical severity. J Intellect Disabil Res. 2012 Mar;56(3):233-47. doi: 10.1111/j.1365-2788.2011.01404.x. Epub 2011 Mar 8.
PubMed 21385260Aman MG, Singh NN (1986) Aberrant Behavior Checklist-Community manual. East Aurora, NY: Slosson Educational publications.
Sansone SM, Widaman KF, Hall SS, Reiss AL, Lightbody A, Kaufmann WE, Berry-Kravis E, Lachiewicz A, Brown EC, Hessl D. Psychometric study of the Aberrant Behavior Checklist in Fragile X Syndrome and implications for targeted treatment. J Autism Dev Disord. 2012 Jul;42(7):1377-92. doi: 10.1007/s10803-011-1370-2.
PubMed 21972117Ji NY, Capone GT, Kaufmann WE. Autism spectrum disorder in Down syndrome: cluster analysis of Aberrant Behaviour Checklist data supports diagnosis. J Intellect Disabil Res. 2011 Nov;55(11):1064-77. doi: 10.1111/j.1365-2788.2011.01465.x. Epub 2011 Aug 30.
PubMed 21883598Barnes KV, Coughlin FR, O'Leary HM, Bruck N, Bazin GA, Beinecke EB, Walco AC, Cantwell NG, Kaufmann WE. Anxiety-like behavior in Rett syndrome: characteristics and assessment by anxiety scales. J Neurodev Disord. 2015;7(1):30. doi: 10.1186/s11689-015-9127-4. Epub 2015 Sep 15.
PubMed 26379794Mount RH, Charman T, Hastings RP, Reilly S, Cass H. The Rett Syndrome Behaviour Questionnaire (RSBQ): refining the behavioural phenotype of Rett syndrome. J Child Psychol Psychiatry. 2002 Nov;43(8):1099-110. doi: 10.1111/1469-7610.00236.
PubMed 12455930Mount RH, Hastings RP, Reilly S, Cass H, Charman T. Behaviour problems in adult women with Rett syndrome. J Intellect Disabil Res. 2002 Nov;46(Pt 8):619-24. doi: 10.1046/j.1365-2788.2002.00442.x.
PubMed 12427169Khwaja OS, Ho E, Barnes KV, O'Leary HM, Pereira LM, Finkelstein Y, Nelson CA 3rd, Vogel-Farley V, DeGregorio G, Holm IA, Khatwa U, Kapur K, Alexander ME, Finnegan DM, Cantwell NG, Walco AC, Rappaport L, Gregas M, Fichorova RN, Shannon MW, Sur M, Kaufmann WE. Safety, pharmacokinetics, and preliminary assessment of efficacy of mecasermin (recombinant human IGF-1) for the treatment of Rett syndrome. Proc Natl Acad Sci U S A. 2014 Mar 25;111(12):4596-601. doi: 10.1073/pnas.1311141111. Epub 2014 Mar 12.
PubMed 24623853Vignoli A, Fabio RA, La Briola F, Giannatiempo S, Antonietti A, Maggiolini S, Canevini MP. Correlations between neurophysiological, behavioral, and cognitive function in Rett syndrome. Epilepsy Behav. 2010 Apr;17(4):489-96. doi: 10.1016/j.yebeh.2010.01.024. Epub 2010 Mar 16.
PubMed 20236870Berry-Kravis E, Hessl D, Abbeduto L, Reiss AL, Beckel-Mitchener A, Urv TK; Outcome Measures Working Groups. Outcome measures for clinical trials in fragile X syndrome. J Dev Behav Pediatr. 2013 Sep;34(7):508-22. doi: 10.1097/DBP.0b013e31829d1f20.
PubMed 24042082Norris M, Lecavalier L. Evaluating the use of exploratory factor analysis in developmental disability psychological research. J Autism Dev Disord. 2010 Jan;40(1):8-20. doi: 10.1007/s10803-009-0816-2. Epub 2009 Jul 17.
PubMed 19609833
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Development of a Behavioral Outcome Measure for Rett Syndrome (RettBe)
- ClinicalTrials.gov ID
- NCT03196323
- Acronym / sponsor ID
- RTT5214
- Conditions
- Rett Syndrome
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 146 participants (actual)
- Lead sponsor
- University of South FloridaUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Center for Advancing Translational Sciences (NCATS), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- 1 Jun 2017 (actual)
- Primary completion
- 24 Sep 2020 (actual)
- Study completion
- 24 Sep 2020 (actual)
- First posted
- 22 Jun 2017 (actual)
- 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 overall purpose of this study is to develop a broad-based (i.e., multiple domains) behavioral outcome measure for children between the ages of 3-18 years with Rett syndrome (RTT). The innovative approach of this proposal consists of integrating the process of developing a behavioral questionnaire to an ongoing large-scale data collection project. The Natural History Study of Rett Syndrome and Related Disorders (RTT5211) is a project that collects data on diverse aspects of the clinical evolution of individuals with RTT and related disorders. This project will serve as the basis for recruitment of subjects and it will also provide key demographic and clinical data for cohort characterization and for determining clinical relevance of the instrument (RettBe). An initial 100-subject cohort will allow for the testing with one rater of RettBe 1.0, a 50-item questionnaire formed from existing measures, a panel of clinicians and behavioral experts in RTT, and a focus group of parents and caregivers of children with RTT. Scores on RettBe 1.0 will be statistically analyzed to determine their psychometric properties, including its content validity. Items that do not meet psychometric standards (e.g., ceiling effect) will be eliminated.
Additional items will be added if the parental survey attached to RettBe 1.0 or clinician input suggests so. The resulting modified assessment, called RettBe 2.0, will be administered to a larger (validation) cohort of 300 participants. RettBe 2.0 will also be subjected to analysis of psychometric properties. RettBe 2.0 will also be administered to two raters per subject, in order to determine inter-rater reliability. In addition, these raters will be completing other behavioral and clinical measures for further evaluating the validity of RettBe 2.0 as well as for determining its clinical and functional significance. Finally, the investigators will obtain input from a panel of clinicians (site PIs and their designated clinicians) about content validity and clinical impact. The resulting version will be released as RettBe 3.0.
Detailed description
Behavioral abnormalities, ranging from autistic symptoms to anxiety and mood lability, are now recognized as major clinical issues in RTT. These clinical manifestations are particularly problematic in higher functioning individuals since they seem to substantially affect their quality of life. Moreover, novel drug treatments aiming at RTT's neurobiological mechanisms have the potential of targeting these abnormal behaviors. Despite the recent emphasis on abnormal behaviors, little is known about their characteristics, severity, and impact. This is due, in part, to the paucity of behavioral measures compatible with the cognitive and motor impairments of RTT. The investigators currently have only one instrument with limited validation for delineating the range of behavioral abnormalities in RTT (the parent-rated Rett Syndrome Behavioral Questionnaire (RSBQ)), which is a significant shortcoming to the implementation of treatment trials. Moreover, there has not been a systematic approach for defining behavioral abnormalities in RTT (e.g., definition of mood abnormalities in RTT). These deficiencies have led the investigators to propose the creation of a broad-based behavioral outcome measure for use in RTT at different ages. Due to the complexity of the clinical evolution of RTT and the relative limited knowledge on its adult period, the investigators will focus on children with RTT ages 3-18 years. The new measure will allow for standardized quantifications of behavioral outcomes in treatment trials and, eventually, in clinical practice. The investigators recognize that developing an instrument with strong psychometric properties is a major endeavor; therefore, the investigators conceived this project as a multi-stage process.
The first stage, conducted with support of Rettsyndrome.org, consisted of developing a prototype or first version of a behavioral questionnaire for parents of children with RTT (3-18 years), which the investigators have termed RettBe 1.0. The initial part of this study will test the psychometric properties (i.e., structure, content validity) of RettBe 1.0 with an initial cohort of 100 participants. This stage intends to transform RettBe 1.0 into a fully developed behavioral instrument within the framework of the Natural History Study (RTT5211). Thus, in Aim 1 the investigators will evaluate psychometrically RettBe 1.0 following, in part, previous studies including their examination of anxiety instruments and adaptation of the Anxiety, Depression and Mood Scale (ADAMS) for RTT, and their adaptations of the Aberrant Behavior Checklist-Community (ABC-C) for fragile X syndrome and Down syndrome. In Aim 1, they will also refine RettBe 1.0 by adding new "missing" items based on parental input or clinician (PIs of sites involved) feedback. The resulting instrument, RettBe 2.0 will be tested in Aim 2.
Testing of RettBe 2.0 will be carried out with a new (naïve) validation cohort of 300 subjects and two raters (preferentially both parents/caregivers, alternatively one teacher or therapist), to determine inter-rater reliability. One rater, preferentially a parent, will be asked to also complete three other behavioral measures (RSBQ, ADAMS, ABC-C) for comparisons. Scores for RettBe 2.0 will be analyzed in terms of psychometric properties, as performed for RettBe 1.0. However, in addition to structure (construct validity) and content validity, the investigators will also examine convergent and discriminant validity by correlating domain RettBe 2.0 scores with those of comparable and non-comparable domain scores of the RSBQ, ADAMS, and ABC-C, respectively.
Finally, Aim 3 will use data from the RTT5211 protocol to determine the effect of age on RettBe 2.0 scores and the clinical and functional significance of the measure. Specifically, the investigators will examine score distributions throughout the age range, with special emphasis on early childhood (3-8 years), late childhood (8-12 years), and adolescence (>12 years). Clinical and functional relevance will be determined by correlations with instruments measuring multiple parameters of clinical severity, specifically, the CGI-S, Clinical Severity Scale, and Motor Behavior Assessment. Relevance to quality of life will be evaluated by correlations with the Child Health Questionnaire-Parent Form 50 (CHQ-PF50; child-oriented measure) and The Short Form (36) Health Survey (SF-36v2TM Health Survey; parent-oriented measure). All these instruments are components of the core RTT5211 protocol. Finally, prior to its release as RettBe 3.0 (if psychometric properties are good-excellent), the investigators will obtain input from a panel of clinicians (site PIs and their designated clinicians) about content validity and clinical impact.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Initial Cohort | – | –In Aim 1, the investigators will evaluate psychometrically RettBe 1.0 following, in part, previous studies including our examination of anxiety instruments and adaptation of the Anxiety, Depression and Mood Scale (ADAMS) for RTT, and their adaptations of the Aberrant Behavior Checklist-Community (ABC-C) for fragile X syndrome and Down syndrome. In Aim 1, the investigators will also refine RettBe 1.0 by adding new "missing" items based on parental input or clinician (PIs of sites involved) feedback. The resulting instrument, RettBe 2.0 will be tested in Aim 2. |
| Validation Cohort | – | –Testing of RettBe 2.0 will be carried out with a new (naïve) validation cohort of 300 subjects and two raters (preferentially both parents/caregivers, alternatively one teacher or therapist), to determine inter-rater reliability. One rater, preferentially a parent, will be asked to also complete three other behavioral measures (RSBQ, ADAMS, ABC-C) for comparisons. Scores for RettBe 2.0 will be analyzed in terms of psychometric properties, as performed for RettBe 1.0. However, in addition to structure (construct validity) and content validity, the investigators will also examine convergent and discriminant validity by correlating domain RettBe 2.0 scores with those of comparable and non-comparable domain scores of the RSBQ, ADAMS, and ABC-C, respectively. |
Who may qualify
- Ages
- 3 to 18 years
- Sex
- Female only
- Age groups
- Child, Adult
- Study population
- A total of 400 subjects with RTT between the ages of 3 and 18 years of age will be recruited from RTT5211, which collects longitudinal clinical and neurobehavioral data in RTT and related disorders. This study will only include participants who meet 2010 diagnostic criteria for classic or atypical RTT and have a MECP2 mutation. Recruitment into this study will come from the larger cohort of those enrolled in the Natural History Study (RTT5211), a study aiming at enrolling 1000 participants with RTT. As a part of the Natural History Study (RTT5211), subjects provide their email address. RTT5211 participants will be emailed an invitation to join this study. Consent and study participation will be done online via a unique link in the invitation.
Key inclusion criteria (10 listed)
- Females 3 - 18 years
- Meets revised 2010 diagnostic criteria for classic or atypical RTT
- Post-regression status
- Documentation of positive MECP2 mutation
- Enrolled in the Natural History Study (RTT5211)
Key exclusion criteria (4 listed)
- Do not meet the above inclusion criteria
- Foster children
- Non-English speakers
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
RettBE 1.0 Score
Time frame: 8 months
Scores from RettBe 1.0, a 50-item questionnaire will be analyzed for psychometric properties, including content validity. RettBe 1.0 scores will be subjected to factor analysis to ensure domain-appropriate balance and structure.
RettBe 2.0 Score
Time frame: 8 months
RettBe 2.0 will be analyzed for psychometric properties. In addition, these raters will be completing other behavioral and clinical/functional measures for further evaluating the validity of RettBe 2.0 as well as for determining its clinical and functional significance (Aim 3). RettBe 2.0 will be subjected to factor analysis to ensure domain-appropriate balance and structure.
RettBe 3.0 Score
Time frame: 8 months
RettBe 3.0 scores will be subjected to factor analysis to ensure domain-appropriate balance and structure.
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 9 Dec 2020.
- 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 16389588Robertson L, Hall SE, Jacoby P, Ellaway C, de Klerk N, Leonard H. The association between behavior and genotype in Rett syndrome using the Australian Rett Syndrome Database. Am J Med Genet B Neuropsychiatr Genet. 2006 Mar 5;141B(2):177-83. doi: 10.1002/ajmg.b.30270.
- Background: PubMed 22013176Lane JB, Lee HS, Smith LW, Cheng P, Percy AK, Glaze DG, Neul JL, Motil KJ, Barrish JO, Skinner SA, Annese F, McNair L, Graham J, Khwaja O, Barnes K, Krischer JP. Clinical severity and quality of life in children and adolescents with Rett syndrome. Neurology. 2011 Nov 15;77(20):1812-8. doi: 10.1212/WNL.0b013e3182377dd2. Epub 2011 Oct 19.
- Background: PubMed 20298210Cobb S, Guy J, Bird A. Reversibility of functional deficits in experimental models of Rett syndrome. Biochem Soc Trans. 2010 Apr;38(2):498-506. doi: 10.1042/BST0380498.
- Background: PubMed 21385260Kaufmann WE, Tierney E, Rohde CA, Suarez-Pedraza MC, Clarke MA, Salorio CF, Bibat G, Bukelis I, Naram D, Lanham DC, Naidu S. Social impairments in Rett syndrome: characteristics and relationship with clinical severity. J Intellect Disabil Res. 2012 Mar;56(3):233-47. doi: 10.1111/j.1365-2788.2011.01404.x. Epub 2011 Mar 8.
- BackgroundAman MG, Singh NN (1986) Aberrant Behavior Checklist-Community manual. East Aurora, NY: Slosson Educational publications.
- Background: PubMed 21972117Sansone SM, Widaman KF, Hall SS, Reiss AL, Lightbody A, Kaufmann WE, Berry-Kravis E, Lachiewicz A, Brown EC, Hessl D. Psychometric study of the Aberrant Behavior Checklist in Fragile X Syndrome and implications for targeted treatment. J Autism Dev Disord. 2012 Jul;42(7):1377-92. doi: 10.1007/s10803-011-1370-2.
- Background: PubMed 21883598Ji NY, Capone GT, Kaufmann WE. Autism spectrum disorder in Down syndrome: cluster analysis of Aberrant Behaviour Checklist data supports diagnosis. J Intellect Disabil Res. 2011 Nov;55(11):1064-77. doi: 10.1111/j.1365-2788.2011.01465.x. Epub 2011 Aug 30.
- Background: PubMed 26379794Barnes KV, Coughlin FR, O'Leary HM, Bruck N, Bazin GA, Beinecke EB, Walco AC, Cantwell NG, Kaufmann WE. Anxiety-like behavior in Rett syndrome: characteristics and assessment by anxiety scales. J Neurodev Disord. 2015;7(1):30. doi: 10.1186/s11689-015-9127-4. Epub 2015 Sep 15.
- Background: PubMed 12455930Mount RH, Charman T, Hastings RP, Reilly S, Cass H. The Rett Syndrome Behaviour Questionnaire (RSBQ): refining the behavioural phenotype of Rett syndrome. J Child Psychol Psychiatry. 2002 Nov;43(8):1099-110. doi: 10.1111/1469-7610.00236.
- Background: PubMed 12427169Mount RH, Hastings RP, Reilly S, Cass H, Charman T. Behaviour problems in adult women with Rett syndrome. J Intellect Disabil Res. 2002 Nov;46(Pt 8):619-24. doi: 10.1046/j.1365-2788.2002.00442.x.
- Background: PubMed 24623853Khwaja OS, Ho E, Barnes KV, O'Leary HM, Pereira LM, Finkelstein Y, Nelson CA 3rd, Vogel-Farley V, DeGregorio G, Holm IA, Khatwa U, Kapur K, Alexander ME, Finnegan DM, Cantwell NG, Walco AC, Rappaport L, Gregas M, Fichorova RN, Shannon MW, Sur M, Kaufmann WE. Safety, pharmacokinetics, and preliminary assessment of efficacy of mecasermin (recombinant human IGF-1) for the treatment of Rett syndrome. Proc Natl Acad Sci U S A. 2014 Mar 25;111(12):4596-601. doi: 10.1073/pnas.1311141111. Epub 2014 Mar 12.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site 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, run by University of South Florida at 1 site 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 10 inclusion and 4 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 9 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
RettBE 1.0 Score (time frame: 8 months). The study lists 3 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 NCT03196323, which also lists 15 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 9 Dec 2020.