Development of a Behavioral Outcome Measure for Rett Syndrome (RettBe)
NCT ID: NCT03196323
Last Updated: 2020-12-09
Study Results
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Basic Information
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COMPLETED
146 participants
OBSERVATIONAL
2017-06-01
2020-09-24
Brief Summary
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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
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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
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Study Design
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COHORT
PROSPECTIVE
Study Groups
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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.
No interventions assigned to this group
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.
No interventions assigned to this group
Eligibility Criteria
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Inclusion Criteria
* 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)
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
* Foster children
* Non-English speakers
Exclusion Criteria
3 Years
18 Years
FEMALE
No
Sponsors
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National Institutes of Health (NIH)
NIH
National Center for Advancing Translational Sciences (NCATS)
NIH
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
NIH
National Institute of Neurological Disorders and Stroke (NINDS)
NIH
University of South Florida
OTHER
Responsible Party
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Locations
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University of South Florida
Tampa, Florida, United States
Countries
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References
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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.
Robertson 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.
Lane 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.
Cobb 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.
Kaufmann 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.
Aman 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.
Ji 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.
Barnes 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.
Mount 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.
Mount 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.
Khwaja 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.
Vignoli 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.
Berry-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.
Norris 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.
Other Identifiers
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RTT5214
Identifier Type: -
Identifier Source: org_study_id