Randomised controlled trial of simvastatin treatment for autism in young children with neurofibromatosis type 1 (SANTA) / S. STIVAROS in Molecular Autism, 9 (2018)  

Public ISBD [article]  inMolecular Autism > 9 (2018) . - 12p. Titre : Randomised controlled trial of simvastatin treatment for autism in young children with neurofibromatosis type 1 (SANTA) Type de document : Texte imprimé et/ou numérique Auteurs : S. STIVAROS, Auteur ; S. GARG, Auteur ; M. TZIRAKI, Auteur ; Y. CAI, Auteur ; O. THOMAS, Auteur ; J. MELLOR, Auteur ; A. A. MORRIS, Auteur ; C. JIM, Auteur ; K. SZUMANSKA-RYT, Auteur ; L. M. PARKES, Auteur ; H. A. HAROON, Auteur ; D. MONTALDI, Auteur ; N. WEBB, Auteur ; J. KEANE, Auteur ; Francisco Xavier CASTELLANOS, Auteur ; A. J. SILVA, Auteur ; S. HUSON, Auteur ; S. WILLIAMS, Auteur ; D. GARETH EVANS, Auteur ; R. EMSLEY, Auteur ; J. GREEN, Auteur Article en page(s) : 12p. Langues : Anglais (eng) Mots-clés : Autism  Neurofibromatosis type 1  Neuroimaging  Randomised controlled trial  Simvastatin  Statin Index. décimale : PER Périodiques Résumé : Background: Neurofibromatosis 1 (NF1) is a monogenic model for syndromic autism. Statins rescue the social and cognitive phenotype in animal knockout models, but translational trials with subjects > 8 years using cognition/behaviour outcomes have shown mixed results. This trial breaks new ground by studying statin effects for the first time in younger children with NF1 and co-morbid autism and by using multiparametric imaging outcomes. Methods: A single-site triple-blind RCT of simvastatin vs. placebo was done. Assessment (baseline and 12-week endpoint) included peripheral MAPK assay, awake magnetic resonance imaging spectroscopy (MRS; GABA and glutamate+glutamine (Glx)), arterial spin labelling (ASL), apparent diffusion coefficient (ADC), resting state functional MRI, and autism behavioural outcomes (Aberrant Behaviour Checklist and Clinical Global Impression). Results: Thirty subjects had a mean age of 8.1 years (SD 1.8). Simvastatin was well tolerated. The amount of imaging data varied by test. Simvastatin treatment was associated with (i) increased frontal white matter MRS GABA (t(12) = - 2.12, p = .055), GABA/Glx ratio (t(12) = - 2.78, p = .016), and reduced grey nuclei Glx (ANCOVA p < 0.05, Mann-Whitney p < 0.01); (ii) increased ASL perfusion in ventral diencephalon (Mann-Whitney p < 0.01); and (iii) decreased ADC in cingulate gyrus (Mann-Whitney p < 0.01). Machine-learning classification of imaging outcomes achieved 79% (p < .05) accuracy differentiating groups at endpoint against chance level (64%, p = 0.25) at baseline. Three of 12 (25%) simvastatin cases compared to none in placebo met 'clinical responder' criteria for behavioural outcome. Conclusions: We show feasibility of peripheral MAPK assay and autism symptom measurement, but the study was not powered to test effectiveness. Multiparametric imaging suggests possible simvastatin effects in brain areas previously associated with NF1 pathophysiology and the social brain network. Trial registration: EU Clinical Trial Register (EudraCT) 2012-005742-38 (www.clinicaltrialsregister.eu). En ligne : http://dx.doi.org/10.1186/s13229-018-0190-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=354 [article] Randomised controlled trial of simvastatin treatment for autism in young children with neurofibromatosis type 1 (SANTA) [Texte imprimé et/ou numérique] / S. STIVAROS, Auteur ; S. GARG, Auteur ; M. TZIRAKI, Auteur ; Y. CAI, Auteur ; O. THOMAS, Auteur ; J. MELLOR, Auteur ; A. A. MORRIS, Auteur ; C. JIM, Auteur ; K. SZUMANSKA-RYT, Auteur ; L. M. PARKES, Auteur ; H. A. HAROON, Auteur ; D. MONTALDI, Auteur ; N. WEBB, Auteur ; J. KEANE, Auteur ; Francisco Xavier CASTELLANOS, Auteur ; A. J. SILVA, Auteur ; S. HUSON, Auteur ; S. WILLIAMS, Auteur ; D. GARETH EVANS, Auteur ; R. EMSLEY, Auteur ; J. GREEN, Auteur . - 12p. Langues : Anglais (eng) in Molecular Autism > 9 (2018) . - 12p. Mots-clés : Autism  Neurofibromatosis type 1  Neuroimaging  Randomised controlled trial  Simvastatin  Statin Index. décimale : PER Périodiques Résumé : Background: Neurofibromatosis 1 (NF1) is a monogenic model for syndromic autism. Statins rescue the social and cognitive phenotype in animal knockout models, but translational trials with subjects > 8 years using cognition/behaviour outcomes have shown mixed results. This trial breaks new ground by studying statin effects for the first time in younger children with NF1 and co-morbid autism and by using multiparametric imaging outcomes. Methods: A single-site triple-blind RCT of simvastatin vs. placebo was done. Assessment (baseline and 12-week endpoint) included peripheral MAPK assay, awake magnetic resonance imaging spectroscopy (MRS; GABA and glutamate+glutamine (Glx)), arterial spin labelling (ASL), apparent diffusion coefficient (ADC), resting state functional MRI, and autism behavioural outcomes (Aberrant Behaviour Checklist and Clinical Global Impression). Results: Thirty subjects had a mean age of 8.1 years (SD 1.8). Simvastatin was well tolerated. The amount of imaging data varied by test. Simvastatin treatment was associated with (i) increased frontal white matter MRS GABA (t(12) = - 2.12, p = .055), GABA/Glx ratio (t(12) = - 2.78, p = .016), and reduced grey nuclei Glx (ANCOVA p < 0.05, Mann-Whitney p < 0.01); (ii) increased ASL perfusion in ventral diencephalon (Mann-Whitney p < 0.01); and (iii) decreased ADC in cingulate gyrus (Mann-Whitney p < 0.01). Machine-learning classification of imaging outcomes achieved 79% (p < .05) accuracy differentiating groups at endpoint against chance level (64%, p = 0.25) at baseline. Three of 12 (25%) simvastatin cases compared to none in placebo met 'clinical responder' criteria for behavioural outcome. Conclusions: We show feasibility of peripheral MAPK assay and autism symptom measurement, but the study was not powered to test effectiveness. Multiparametric imaging suggests possible simvastatin effects in brain areas previously associated with NF1 pathophysiology and the social brain network. Trial registration: EU Clinical Trial Register (EudraCT) 2012-005742-38 (www.clinicaltrialsregister.eu). En ligne : http://dx.doi.org/10.1186/s13229-018-0190-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=354

The Autism Family Experience Questionnaire (AFEQ): An Ecologically-Valid, Parent-Nominated Measure of Family Experience, Quality of Life and Prioritised Outcomes for Early Intervention / K. LEADBITTER in Journal of Autism and Developmental Disorders, 48-4 (April 2018)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 48-4 (April 2018) . - p.1052-1062 Titre : The Autism Family Experience Questionnaire (AFEQ): An Ecologically-Valid, Parent-Nominated Measure of Family Experience, Quality of Life and Prioritised Outcomes for Early Intervention Type de document : Texte imprimé et/ou numérique Auteurs : K. LEADBITTER, Auteur ; Catherine ALDRED, Auteur ; H. MCCONACHIE, Auteur ; A. LE COUTEUR, Auteur ; D. KAPADIA, Auteur ; Tony CHARMAN, Auteur ; W. MACDONALD, Auteur ; E. SALOMONE, Auteur ; R. EMSLEY, Auteur ; J. GREEN, Auteur Article en page(s) : p.1052-1062 Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder  Family experience  Intervention  Parent  Quality of Life  Wellbeing Index. décimale : PER Périodiques Résumé : There is a lack of measures that reflect the intervention priorities of parents of children with autism spectrum disorder (ASD) and that assess the impact of interventions on family experience and quality of life. The Autism Family Experience Questionnaire (AFEQ) was developed through focus groups and online consultation with parents, and reflected parental priorities. It was then administered to the parents of children enrolled in the Pre-school Autism Communication Trial and its 6-year follow-up study. The AFEQ showed good convergent validity with well-established measures of child adaptive functioning, parental mental health and parental wellbeing. It was sensitive to change in response to a parent-mediated intervention for young children with autism, showing treatment effect at treatment endpoint which increased at six-year follow-up. En ligne : http://dx.doi.org/10.1007/s10803-017-3350-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=351 [article] The Autism Family Experience Questionnaire (AFEQ): An Ecologically-Valid, Parent-Nominated Measure of Family Experience, Quality of Life and Prioritised Outcomes for Early Intervention [Texte imprimé et/ou numérique] / K. LEADBITTER, Auteur ; Catherine ALDRED, Auteur ; H. MCCONACHIE, Auteur ; A. LE COUTEUR, Auteur ; D. KAPADIA, Auteur ; Tony CHARMAN, Auteur ; W. MACDONALD, Auteur ; E. SALOMONE, Auteur ; R. EMSLEY, Auteur ; J. GREEN, Auteur . - p.1052-1062. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 48-4 (April 2018) . - p.1052-1062 Mots-clés : Autism Spectrum Disorder  Family experience  Intervention  Parent  Quality of Life  Wellbeing Index. décimale : PER Périodiques Résumé : There is a lack of measures that reflect the intervention priorities of parents of children with autism spectrum disorder (ASD) and that assess the impact of interventions on family experience and quality of life. The Autism Family Experience Questionnaire (AFEQ) was developed through focus groups and online consultation with parents, and reflected parental priorities. It was then administered to the parents of children enrolled in the Pre-school Autism Communication Trial and its 6-year follow-up study. The AFEQ showed good convergent validity with well-established measures of child adaptive functioning, parental mental health and parental wellbeing. It was sensitive to change in response to a parent-mediated intervention for young children with autism, showing treatment effect at treatment endpoint which increased at six-year follow-up. En ligne : http://dx.doi.org/10.1007/s10803-017-3350-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=351

The Feasibility and Effectiveness of PASS Plus, A Lay Health Worker Delivered Comprehensive Intervention for Autism Spectrum Disorders: Pilot RCT in a Rural Low and Middle Income Country Setting / G. DIVAN in Autism Research, 12-2 (February 2019)  

Public ISBD [article]  inAutism Research > 12-2 (February 2019) . - p.328-339 Titre : The Feasibility and Effectiveness of PASS Plus, A Lay Health Worker Delivered Comprehensive Intervention for Autism Spectrum Disorders: Pilot RCT in a Rural Low and Middle Income Country Setting Type de document : Texte imprimé et/ou numérique Auteurs : G. DIVAN, Auteur ; V. VAJARATKAR, Auteur ; P. CARDOZO, Auteur ; S. HUZURBAZAR, Auteur ; M. VERMA, Auteur ; E. HOWARTH, Auteur ; R. EMSLEY, Auteur ; C. TAYLOR, Auteur ; V. PATEL, Auteur ; J. GREEN, Auteur Article en page(s) : p.328-339 Langues : Anglais (eng) Mots-clés : clinical trials  co-morbid conditions  intervention  parent-mediated  task sharing Index. décimale : PER Périodiques Résumé : The treatment gap for autism globally is high. Our previous PASS intervention, delivered by community based lay health workers, showed effectiveness. This article reports the development and evaluation of a new "PASS 'Plus'" intervention in a rural population in India. Using formative research methods, we supplemented the PASS intervention with additional (Plus) modules to address autism comorbidities. This is the first time that a rigorous methodology has been used to evaluate autism symptom outcomes in a low and middle-income country setting. 40 parent-child dyads were recruited in a pilot randomized controlled trial against usual care (mean age 65 months (34 boys); n = 19 PASS Plus, n = 21 UC). 89% of intervention families partially or entirely completed the 12-session intervention. Intention to treat analysis showed a reduction in mean scores of autism symptom severity, though the confidence interval contains zero, (adjusted mean difference AMD -2.42 95% CI -7.75, 2.92; ES 0.22); large treatment effects on proximal outcomes of proportion of parent synchronous responses (AMD 0.35; 95% CI 0.18, 0.52; effect size ES 3.97) and proportion of child communication initiations with parent (AMD 0.17; 95% CI 0.03, 0.32; ES 1.02). Confidence intervals for effects on mutual shared attention (AMD 0.10; 95% CI -0.07, 0.27; ES 0.5) and co-morbid symptoms (AMD -9.0; 95% CI -24.26, 6.26; ES 0.32) contained zero. There were significant effects to improve parental mental health. PASS Plus shows good feasibility and adds to the evidence of the effectiveness of task sharing complex autism interventions to lay health workers in India. Autism Res 2019, 12: 328-339 (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This article describes the development of a comprehensive, community-delivered, intervention for young children with autism, which combines a previously developed parent-mediated communication intervention with support for co-morbid problems like challenging behaviors and sensory sensitivities. The unique aspect of this intervention is that it can be delivered by community health workers, addressing the lack of specialists in low resource settings. Our study reports the encouraging findings of a pilot trial evaluating its feasibility and effectiveness. En ligne : http://dx.doi.org/10.1002/aur.1978 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=383 [article] The Feasibility and Effectiveness of PASS Plus, A Lay Health Worker Delivered Comprehensive Intervention for Autism Spectrum Disorders: Pilot RCT in a Rural Low and Middle Income Country Setting [Texte imprimé et/ou numérique] / G. DIVAN, Auteur ; V. VAJARATKAR, Auteur ; P. CARDOZO, Auteur ; S. HUZURBAZAR, Auteur ; M. VERMA, Auteur ; E. HOWARTH, Auteur ; R. EMSLEY, Auteur ; C. TAYLOR, Auteur ; V. PATEL, Auteur ; J. GREEN, Auteur . - p.328-339. Langues : Anglais (eng) in Autism Research > 12-2 (February 2019) . - p.328-339 Mots-clés : clinical trials  co-morbid conditions  intervention  parent-mediated  task sharing Index. décimale : PER Périodiques Résumé : The treatment gap for autism globally is high. Our previous PASS intervention, delivered by community based lay health workers, showed effectiveness. This article reports the development and evaluation of a new "PASS 'Plus'" intervention in a rural population in India. Using formative research methods, we supplemented the PASS intervention with additional (Plus) modules to address autism comorbidities. This is the first time that a rigorous methodology has been used to evaluate autism symptom outcomes in a low and middle-income country setting. 40 parent-child dyads were recruited in a pilot randomized controlled trial against usual care (mean age 65 months (34 boys); n = 19 PASS Plus, n = 21 UC). 89% of intervention families partially or entirely completed the 12-session intervention. Intention to treat analysis showed a reduction in mean scores of autism symptom severity, though the confidence interval contains zero, (adjusted mean difference AMD -2.42 95% CI -7.75, 2.92; ES 0.22); large treatment effects on proximal outcomes of proportion of parent synchronous responses (AMD 0.35; 95% CI 0.18, 0.52; effect size ES 3.97) and proportion of child communication initiations with parent (AMD 0.17; 95% CI 0.03, 0.32; ES 1.02). Confidence intervals for effects on mutual shared attention (AMD 0.10; 95% CI -0.07, 0.27; ES 0.5) and co-morbid symptoms (AMD -9.0; 95% CI -24.26, 6.26; ES 0.32) contained zero. There were significant effects to improve parental mental health. PASS Plus shows good feasibility and adds to the evidence of the effectiveness of task sharing complex autism interventions to lay health workers in India. Autism Res 2019, 12: 328-339 (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This article describes the development of a comprehensive, community-delivered, intervention for young children with autism, which combines a previously developed parent-mediated communication intervention with support for co-morbid problems like challenging behaviors and sensory sensitivities. The unique aspect of this intervention is that it can be delivered by community health workers, addressing the lack of specialists in low resource settings. Our study reports the encouraging findings of a pilot trial evaluating its feasibility and effectiveness. En ligne : http://dx.doi.org/10.1002/aur.1978 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=383

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