Development of a Behavioral Outcome Measure for Rett Syndrome (RettBe)

NCT03196323 | Completed DMC

• 1 other identifier: RTT5214
• Study Type: observational
• Target: 146
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Rett Syndrome

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  8 months

• RettBe 3.0 Score

  RettBe 3.0 scores will be subjected to factor analysis to ensure domain-appropriate balance and structure.

  8 months

Study Arms (2)

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.

Eligibility Criteria

• Age: 3 Years - 18 Years
• Sex: female
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

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.

You may qualify if:

• 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)
• 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

You may not qualify if:

• Both RettBe 1.0 and RettBe 2.0:
• Foster children
• Non-English speakers

Sponsors & Collaborators

• University of South Florida: lead
• National Institutes of Health (NIH): collaborator
• National Center for Advancing Translational Sciences (NCATS): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

University of South Florida

Tampa, Florida, 33612, United States

Location

Related Publications (15)

• 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.

  PMID: 21154482 BACKGROUND

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  PMID: 16389588 BACKGROUND

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  PMID: 20298210 BACKGROUND

• 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.

  PMID: 21385260 BACKGROUND

• Aman MG, Singh NN (1986) Aberrant Behavior Checklist-Community manual. East Aurora, NY: Slosson Educational publications.

  BACKGROUND

• 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.

  PMID: 21972117 BACKGROUND

• 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.

  PMID: 21883598 BACKGROUND

• 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.

  PMID: 26379794 BACKGROUND

• 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.

  PMID: 12455930 BACKGROUND

• 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.

  PMID: 12427169 BACKGROUND

• 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.

  PMID: 24623853 BACKGROUND

• 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.

  PMID: 20236870 BACKGROUND

• 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.

  PMID: 24042082 BACKGROUND

• 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.

  PMID: 19609833 BACKGROUND

MeSH Terms

Conditions

Rett Syndrome

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2017
• First Posted: June 22, 2017
• Study Start: June 1, 2017
• Primary Completion: September 24, 2020
• Study Completion: September 24, 2020
• Last Updated: December 9, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)