Adaptive behavior in autism: Minimal clinically important differences on the Vineland?II / Christopher H. CHATHAM in Autism Research, 11-2 (February 2018)  

Public ISBD [article]  inAutism Research > 11-2 (February 2018) . - p.270-283 Titre : Adaptive behavior in autism: Minimal clinically important differences on the Vineland?II Type de document : Texte imprimé et/ou numérique Auteurs : Christopher H. CHATHAM, Auteur ; K. I. TAYLOR, Auteur ; Tony CHARMAN, Auteur ; X. Liogier D'ARDHUY, Auteur ; E. EULE, Auteur ; A. FEDELE, Auteur ; A. Y. HARDAN, Auteur ; E. LOTH, Auteur ; L. MURTAGH, Auteur ; M. del Valle RUBIDO, Auteur ; Antonia SAN JOSE CACERES, Auteur ; J. SEVIGNY, Auteur ; L. SIKICH, Auteur ; L. SNYDER, Auteur ; J. E. TILLMANN, Auteur ; Pamela VENTOLA, Auteur ; Karen WALTON-BOWEN, Auteur ; P. P. WANG, Auteur ; T. WILLGOSS, Auteur ; Federico BOLOGNANI, Auteur Année de publication : 2018 Article en page(s) : p.270-283 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Autism Spectrum Disorder (ASD) is associated with persistent impairments in adaptive abilities across multiple domains. These social, personal, and communicative impairments become increasingly pronounced with development, and are present regardless of IQ. The Vineland Adaptive Behavior Scales, Second Edition (Vineland?II) is the most commonly used instrument for quantifying these impairments, but minimal clinically important differences (MCIDs) on Vineland?II scores have not been rigorously established in ASD. We pooled data from several consortia/registries (EU?AIMS LEAP study, ABIDE?I, ABIDE?II, INFOR, Simons Simplex Collection and Autism Treatment Network [ATN]) and clinical investigations and trials (Stanford, Yale, Roche) resulting in a data set of over 9,000 individuals with ASD. Two approaches were used to estimate MCIDs: distribution?based methods and anchor?based methods. Distribution?based MCID [d?MCID] estimates included the standard error of the measurement, as well as one?fifth and one?half of the covariate?adjusted standard deviation (both cross?sectionally and longitudinally). Anchor?based MCID [a?MCID] estimates include the slope of linear regression of clinician ratings of severity on the Vineland?II score, the slope of linear regression of clinician ratings of longitudinal improvement category on Vineland?II change, the Vineland?II change score maximally differentiating clinical impressions of minimal versus no improvement, and equipercentile equating. Across strata, the Vineland?II Adaptive Behavior Composite standardized score MCID estimates range from 2.01 to 3.2 for distribution?based methods, and from 2.42 to 3.75 for sample?size?weighted anchor?based methods. Lower Vineland?II standardized score MCID estimates were observed for younger and more cognitively impaired populations. These MCID estimates enable users of Vineland?II to assess both the statistical and clinical significance of any observed change. Autism Res 2018, 11: 270–283. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary The Vineland Adaptive Behavior Scales (2nd edition; Vineland?II) is the most widely used scale for assessing day?to?day “adaptive” skills. Yet, it is unknown how much Vineland?II scores must change for those changes to be regarded as clinically significant. We pooled data from over 9,000 individuals with ASD to show that changes of 2–3.75 points on the Vineland?II Composite score represent the “minimal clinically?important difference.” These estimates will help evaluate the benefits of potential new treatments for ASD. En ligne : https://doi.org/10.1002/aur.1874 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=334 [article] Adaptive behavior in autism: Minimal clinically important differences on the Vineland?II [Texte imprimé et/ou numérique] / Christopher H. CHATHAM, Auteur ; K. I. TAYLOR, Auteur ; Tony CHARMAN, Auteur ; X. Liogier D'ARDHUY, Auteur ; E. EULE, Auteur ; A. FEDELE, Auteur ; A. Y. HARDAN, Auteur ; E. LOTH, Auteur ; L. MURTAGH, Auteur ; M. del Valle RUBIDO, Auteur ; Antonia SAN JOSE CACERES, Auteur ; J. SEVIGNY, Auteur ; L. SIKICH, Auteur ; L. SNYDER, Auteur ; J. E. TILLMANN, Auteur ; Pamela VENTOLA, Auteur ; Karen WALTON-BOWEN, Auteur ; P. P. WANG, Auteur ; T. WILLGOSS, Auteur ; Federico BOLOGNANI, Auteur . - 2018 . - p.270-283. Langues : Anglais (eng) in Autism Research > 11-2 (February 2018) . - p.270-283 Index. décimale : PER Périodiques Résumé : Autism Spectrum Disorder (ASD) is associated with persistent impairments in adaptive abilities across multiple domains. These social, personal, and communicative impairments become increasingly pronounced with development, and are present regardless of IQ. The Vineland Adaptive Behavior Scales, Second Edition (Vineland?II) is the most commonly used instrument for quantifying these impairments, but minimal clinically important differences (MCIDs) on Vineland?II scores have not been rigorously established in ASD. We pooled data from several consortia/registries (EU?AIMS LEAP study, ABIDE?I, ABIDE?II, INFOR, Simons Simplex Collection and Autism Treatment Network [ATN]) and clinical investigations and trials (Stanford, Yale, Roche) resulting in a data set of over 9,000 individuals with ASD. Two approaches were used to estimate MCIDs: distribution?based methods and anchor?based methods. Distribution?based MCID [d?MCID] estimates included the standard error of the measurement, as well as one?fifth and one?half of the covariate?adjusted standard deviation (both cross?sectionally and longitudinally). Anchor?based MCID [a?MCID] estimates include the slope of linear regression of clinician ratings of severity on the Vineland?II score, the slope of linear regression of clinician ratings of longitudinal improvement category on Vineland?II change, the Vineland?II change score maximally differentiating clinical impressions of minimal versus no improvement, and equipercentile equating. Across strata, the Vineland?II Adaptive Behavior Composite standardized score MCID estimates range from 2.01 to 3.2 for distribution?based methods, and from 2.42 to 3.75 for sample?size?weighted anchor?based methods. Lower Vineland?II standardized score MCID estimates were observed for younger and more cognitively impaired populations. These MCID estimates enable users of Vineland?II to assess both the statistical and clinical significance of any observed change. Autism Res 2018, 11: 270–283. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary The Vineland Adaptive Behavior Scales (2nd edition; Vineland?II) is the most widely used scale for assessing day?to?day “adaptive” skills. Yet, it is unknown how much Vineland?II scores must change for those changes to be regarded as clinically significant. We pooled data from over 9,000 individuals with ASD to show that changes of 2–3.75 points on the Vineland?II Composite score represent the “minimal clinically?important difference.” These estimates will help evaluate the benefits of potential new treatments for ASD. En ligne : https://doi.org/10.1002/aur.1874 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=334

Arbaclofen in fragile X syndrome: results of phase 3 trials / Elizabeth BERRY-KRAVIS in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.3 Titre : Arbaclofen in fragile X syndrome: results of phase 3 trials Type de document : Texte imprimé et/ou numérique Auteurs : Elizabeth BERRY-KRAVIS, Auteur ; Randi J. HAGERMAN, Auteur ; J. VISOOTSAK, Auteur ; Dejan B. BUDIMIROVIC, Auteur ; W. E. KAUFMANN, Auteur ; M. CHERUBINI, Auteur ; P. ZAREVICS, Auteur ; Karen WALTON-BOWEN, Auteur ; P. WANG, Auteur ; Mark F. BEAR, Auteur ; Randall L. CARPENTER, Auteur Article en page(s) : p.3 Langues : Anglais (eng) Mots-clés : Arbaclofen  Fmr1  Fragile X syndrome  GABA agonist  Neurodevelopmental disorder  Targeted treatment Index. décimale : PER Périodiques Résumé : BACKGROUND: Arbaclofen improved multiple abnormal phenotypes in animal models of fragile X syndrome (FXS) and showed promising results in a phase 2 clinical study. The objective of the study is to determine safety and efficacy of arbaclofen for social avoidance in FXS. METHODS: Two phase 3 placebo-controlled trials were conducted, a flexible dose trial in subjects age 12-50 (209FX301, adolescent/adult study) and a fixed dose trial in subjects age 5-11 (209FX302, child study). The primary endpoint for both trials was the Social Avoidance subscale of the Aberrant Behavior Checklist-Community Edition, FXS-specific (ABC-CFX). Secondary outcomes included other ABC-CFX subscale scores, Clinical Global Impression-Improvement (CGI-I), Clinical Global Impression-Severity (CGI-S), and Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) Socialization domain score. RESULTS: A total 119 of 125 randomized subjects completed the adolescent/adult study (n = 57 arbaclofen, 62 placebo) and 159/172 completed the child study (arbaclofen 5 BID n = 38; 10 BID n = 39; 10 TID n = 38; placebo n = 44). There were no serious adverse events (AEs); the most common AEs included somatic (headache, vomiting, nausea), neurobehavioral (irritability/agitation, anxiety, hyperactivity), decreased appetite, and infectious conditions, many of which were also common on placebo. In the combined studies, there were 13 discontinuations (n = 12 arbaclofen, 1 placebo) due to AEs (all neurobehavioral). The adolescent/adult study did not show benefit for arbaclofen over placebo for any measure. In the child study, the highest dose group showed benefit over placebo on the ABC-CFX Irritability subscale (p = 0.03) and Parenting Stress Index (PSI, p = 0.03) and trends toward benefit on the ABC-CFX Social Avoidance and Hyperactivity subscales (both p < 0.1) and CGI-I (p = 0.119). Effect size in the highest dose group was similar to effect sizes for FDA-approved serotonin reuptake inhibitors (SSRIs). CONCLUSIONS: Arbaclofen did not meet the primary outcome of improved social avoidance in FXS in either study. Data from secondary measures in the child study suggests younger patients may derive benefit, but additional studies with a larger cohort on higher doses would be required to confirm this finding. The reported studies illustrate the challenges but represent a significant step forward in translating targeted treatments from preclinical models to clinical trials in humans with FXS. En ligne : http://dx.doi.org/10.1186/s11689-016-9181-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Arbaclofen in fragile X syndrome: results of phase 3 trials [Texte imprimé et/ou numérique] / Elizabeth BERRY-KRAVIS, Auteur ; Randi J. HAGERMAN, Auteur ; J. VISOOTSAK, Auteur ; Dejan B. BUDIMIROVIC, Auteur ; W. E. KAUFMANN, Auteur ; M. CHERUBINI, Auteur ; P. ZAREVICS, Auteur ; Karen WALTON-BOWEN, Auteur ; P. WANG, Auteur ; Mark F. BEAR, Auteur ; Randall L. CARPENTER, Auteur . - p.3. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.3 Mots-clés : Arbaclofen  Fmr1  Fragile X syndrome  GABA agonist  Neurodevelopmental disorder  Targeted treatment Index. décimale : PER Périodiques Résumé : BACKGROUND: Arbaclofen improved multiple abnormal phenotypes in animal models of fragile X syndrome (FXS) and showed promising results in a phase 2 clinical study. The objective of the study is to determine safety and efficacy of arbaclofen for social avoidance in FXS. METHODS: Two phase 3 placebo-controlled trials were conducted, a flexible dose trial in subjects age 12-50 (209FX301, adolescent/adult study) and a fixed dose trial in subjects age 5-11 (209FX302, child study). The primary endpoint for both trials was the Social Avoidance subscale of the Aberrant Behavior Checklist-Community Edition, FXS-specific (ABC-CFX). Secondary outcomes included other ABC-CFX subscale scores, Clinical Global Impression-Improvement (CGI-I), Clinical Global Impression-Severity (CGI-S), and Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) Socialization domain score. RESULTS: A total 119 of 125 randomized subjects completed the adolescent/adult study (n = 57 arbaclofen, 62 placebo) and 159/172 completed the child study (arbaclofen 5 BID n = 38; 10 BID n = 39; 10 TID n = 38; placebo n = 44). There were no serious adverse events (AEs); the most common AEs included somatic (headache, vomiting, nausea), neurobehavioral (irritability/agitation, anxiety, hyperactivity), decreased appetite, and infectious conditions, many of which were also common on placebo. In the combined studies, there were 13 discontinuations (n = 12 arbaclofen, 1 placebo) due to AEs (all neurobehavioral). The adolescent/adult study did not show benefit for arbaclofen over placebo for any measure. In the child study, the highest dose group showed benefit over placebo on the ABC-CFX Irritability subscale (p = 0.03) and Parenting Stress Index (PSI, p = 0.03) and trends toward benefit on the ABC-CFX Social Avoidance and Hyperactivity subscales (both p < 0.1) and CGI-I (p = 0.119). Effect size in the highest dose group was similar to effect sizes for FDA-approved serotonin reuptake inhibitors (SSRIs). CONCLUSIONS: Arbaclofen did not meet the primary outcome of improved social avoidance in FXS in either study. Data from secondary measures in the child study suggests younger patients may derive benefit, but additional studies with a larger cohort on higher doses would be required to confirm this finding. The reported studies illustrate the challenges but represent a significant step forward in translating targeted treatments from preclinical models to clinical trials in humans with FXS. En ligne : http://dx.doi.org/10.1186/s11689-016-9181-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

STX209 (Arbaclofen) for Autism Spectrum Disorders: An 8-Week Open-Label Study / Craig ERICKSON in Journal of Autism and Developmental Disorders, 44-4 (April 2014)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 44-4 (April 2014) . - p.958-964 Titre : STX209 (Arbaclofen) for Autism Spectrum Disorders: An 8-Week Open-Label Study Type de document : Texte imprimé et/ou numérique Auteurs : Craig ERICKSON, Auteur ; Jeremy M. VEENSTRA-VANDERWEELE, Auteur ; Raun D. MELMED, Auteur ; James T. MCCRACKEN, Auteur ; Lawrence D. GINSBERG, Auteur ; Linmarie SIKICH, Auteur ; Lawrence SCAHILL, Auteur ; Maryann CHERUBINI, Auteur ; Peter ZAREVICS, Auteur ; Karen WALTON-BOWEN, Auteur ; Randall L. CARPENTER, Auteur ; Mark F. BEAR, Auteur ; Paul P. WANG, Auteur ; Bryan H. KING, Auteur Année de publication : 2014 Article en page(s) : p.958-964 Langues : Anglais (eng) Mots-clés : STX209  Arbaclofen  Gamma-aminobutyric acid (GABA)  Autism spectrum disorder  Clinical trial Index. décimale : PER Périodiques Résumé : STX209 (arbaclofen), a selective GABA-B agonist, is hypothesized to modulate the balance of excitatory to inhibitory neurotransmission, and has shown preliminary evidence of benefit in fragile X syndrome. We evaluated its safety, tolerability, and efficacy in non-syndromic autism spectrum disorders, in an 8-week open-label trial enrolling 32 children and adolescents with either Autistic Disorder or Pervasive Developmental Disorder—Not Otherwise Specified, and a score ?17 on the Aberrant Behavior Checklist (ABC)—Irritability subscale. STX209 was generally well-tolerated. The most common adverse events were agitation and irritability, which typically resolved without dose changes, and were often felt to represent spontaneous variation in underlying symptoms. Improvements were observed on several outcome measures in this exploratory trial, including the ABC-Irritability (the primary endpoint) and the Lethargy/Social Withdrawal subscales, the Social Responsiveness Scale, the CY-BOCS-PDD, and clinical global impression scales. Placebo-controlled study of STX209 is warranted. En ligne : http://dx.doi.org/10.1007/s10803-013-1963-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=228 [article] STX209 (Arbaclofen) for Autism Spectrum Disorders: An 8-Week Open-Label Study [Texte imprimé et/ou numérique] / Craig ERICKSON, Auteur ; Jeremy M. VEENSTRA-VANDERWEELE, Auteur ; Raun D. MELMED, Auteur ; James T. MCCRACKEN, Auteur ; Lawrence D. GINSBERG, Auteur ; Linmarie SIKICH, Auteur ; Lawrence SCAHILL, Auteur ; Maryann CHERUBINI, Auteur ; Peter ZAREVICS, Auteur ; Karen WALTON-BOWEN, Auteur ; Randall L. CARPENTER, Auteur ; Mark F. BEAR, Auteur ; Paul P. WANG, Auteur ; Bryan H. KING, Auteur . - 2014 . - p.958-964. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 44-4 (April 2014) . - p.958-964 Mots-clés : STX209  Arbaclofen  Gamma-aminobutyric acid (GABA)  Autism spectrum disorder  Clinical trial Index. décimale : PER Périodiques Résumé : STX209 (arbaclofen), a selective GABA-B agonist, is hypothesized to modulate the balance of excitatory to inhibitory neurotransmission, and has shown preliminary evidence of benefit in fragile X syndrome. We evaluated its safety, tolerability, and efficacy in non-syndromic autism spectrum disorders, in an 8-week open-label trial enrolling 32 children and adolescents with either Autistic Disorder or Pervasive Developmental Disorder—Not Otherwise Specified, and a score ?17 on the Aberrant Behavior Checklist (ABC)—Irritability subscale. STX209 was generally well-tolerated. The most common adverse events were agitation and irritability, which typically resolved without dose changes, and were often felt to represent spontaneous variation in underlying symptoms. Improvements were observed on several outcome measures in this exploratory trial, including the ABC-Irritability (the primary endpoint) and the Lethargy/Social Withdrawal subscales, the Social Responsiveness Scale, the CY-BOCS-PDD, and clinical global impression scales. Placebo-controlled study of STX209 is warranted. En ligne : http://dx.doi.org/10.1007/s10803-013-1963-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=228

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