d-Cycloserine enhances durability of social skills training in autism spectrum disorder / L. K. WINK in Molecular Autism, 8 (2017)  

Public ISBD [article]  inMolecular Autism > 8 (2017) . - 2p. Titre : d-Cycloserine enhances durability of social skills training in autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : L. K. WINK, Auteur ; N. F. MINSHAWI, Auteur ; R. C. SHAFFER, Auteur ; M. H. PLAWECKI, Auteur ; D. J. POSEY, Auteur ; P. S. HORN, Auteur ; R. ADAMS, Auteur ; Ernest V. PEDAPATI, Auteur ; T. L. SCHAEFER, Auteur ; C. J. MCDOUGLE, Auteur ; N. B. SWIEZY, Auteur ; C. A. ERICKSON, Auteur Article en page(s) : 2p. Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/*drug therapy/psychology  Child  Child, Preschool  Cycloserine/*administration & dosage/pharmacology  Double-Blind Method  Drug Administration Schedule  Female  Humans  Learning/*drug effects  Male  Severity of Illness Index  Social Behavior  Treatment Outcome  *Autism  *Autism spectrum disorder  *Social skills training  *d-Cycloserine Index. décimale : PER Périodiques Résumé : BACKGROUND: d-Cycloserine (DCS) enhances extinction learning across species, but it has proven challenging to identify consistent benefit of DCS when added to therapeutic interventions. We conducted a placebo-controlled trial of DCS to potentiate social skills training in autism spectrum disorder (ASD) but found substantial improvement in both the DCS and placebo groups at the conclusion of active treatment. Here, we assess the impact of DCS 11 weeks following active treatment to evaluate the impact of DCS on treatment response durability. METHODS: Study participants included 60 outpatient youth with ASD, ages 5-11 years, all with IQ above 70, and significantly impaired social functioning who completed a 10-week active treatment phase during which they received weekly single doses of 50 mg of DCS or placebo administered 30 min prior to group social skills training. Following the 10-week active treatment phase, blinded follow-up assessments occurred at week 11 and week 22. The primary outcome measure for our durability of treatment evaluation was the parent-rated social responsiveness scale (SRS) total raw score at week 22. RESULTS: Analysis of the SRS total raw score demonstrated significant decrease for the DCS group compared to the placebo group (p = 0.042) indicating greater maintenance of treatment effect in the DCS group. DCS was well tolerated, with irritability being the most frequently reported adverse effect in both groups. CONCLUSIONS: The findings of this study suggest that DCS may help youth with ASD to maintain skills gained during sort-term social skills training. Larger-scale studies with longer follow-up will be necessary to further understand the long-term impact of DCS paired with structured social skills training. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01086475. En ligne : http://dx.doi.org/10.1186/s13229-017-0116-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=331 [article] d-Cycloserine enhances durability of social skills training in autism spectrum disorder [Texte imprimé et/ou numérique] / L. K. WINK, Auteur ; N. F. MINSHAWI, Auteur ; R. C. SHAFFER, Auteur ; M. H. PLAWECKI, Auteur ; D. J. POSEY, Auteur ; P. S. HORN, Auteur ; R. ADAMS, Auteur ; Ernest V. PEDAPATI, Auteur ; T. L. SCHAEFER, Auteur ; C. J. MCDOUGLE, Auteur ; N. B. SWIEZY, Auteur ; C. A. ERICKSON, Auteur . - 2p. Langues : Anglais (eng) in Molecular Autism > 8 (2017) . - 2p. Mots-clés : Autism Spectrum Disorder/*drug therapy/psychology  Child  Child, Preschool  Cycloserine/*administration & dosage/pharmacology  Double-Blind Method  Drug Administration Schedule  Female  Humans  Learning/*drug effects  Male  Severity of Illness Index  Social Behavior  Treatment Outcome  *Autism  *Autism spectrum disorder  *Social skills training  *d-Cycloserine Index. décimale : PER Périodiques Résumé : BACKGROUND: d-Cycloserine (DCS) enhances extinction learning across species, but it has proven challenging to identify consistent benefit of DCS when added to therapeutic interventions. We conducted a placebo-controlled trial of DCS to potentiate social skills training in autism spectrum disorder (ASD) but found substantial improvement in both the DCS and placebo groups at the conclusion of active treatment. Here, we assess the impact of DCS 11 weeks following active treatment to evaluate the impact of DCS on treatment response durability. METHODS: Study participants included 60 outpatient youth with ASD, ages 5-11 years, all with IQ above 70, and significantly impaired social functioning who completed a 10-week active treatment phase during which they received weekly single doses of 50 mg of DCS or placebo administered 30 min prior to group social skills training. Following the 10-week active treatment phase, blinded follow-up assessments occurred at week 11 and week 22. The primary outcome measure for our durability of treatment evaluation was the parent-rated social responsiveness scale (SRS) total raw score at week 22. RESULTS: Analysis of the SRS total raw score demonstrated significant decrease for the DCS group compared to the placebo group (p = 0.042) indicating greater maintenance of treatment effect in the DCS group. DCS was well tolerated, with irritability being the most frequently reported adverse effect in both groups. CONCLUSIONS: The findings of this study suggest that DCS may help youth with ASD to maintain skills gained during sort-term social skills training. Larger-scale studies with longer follow-up will be necessary to further understand the long-term impact of DCS paired with structured social skills training. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01086475. En ligne : http://dx.doi.org/10.1186/s13229-017-0116-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=331

A randomized placebo-controlled pilot study of N-acetylcysteine in youth with autism spectrum disorder / L. K. WINK in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 26p. Titre : A randomized placebo-controlled pilot study of N-acetylcysteine in youth with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : L. K. WINK, Auteur ; R. ADAMS, Auteur ; Z. WANG, Auteur ; J. E. KLAUNIG, Auteur ; M. H. PLAWECKI, Auteur ; D. J. POSEY, Auteur ; C. J. MCDOUGLE, Auteur ; C. A. ERICKSON, Auteur Article en page(s) : 26p. Langues : Anglais (eng) Mots-clés : Acetylcysteine/pharmacology/therapeutic use  Administration, Oral  Autism Spectrum Disorder/drug therapy  Child  Child, Preschool  Comet Assay  DNA Damage/drug effects  Double-Blind Method  Drug Administration Schedule  Female  Follow-Up Studies  Free Radical Scavengers/pharmacology/therapeutic use  Glutathione/blood  Homocysteine/blood  Humans  Male  Oxidation-Reduction  Oxidative Stress/drug effects  Pilot Projects  Placebo Effect  Social Behavior  Autism  Autism spectrum disorder  N-acetylcysteine  Oxidative stress  Social impairment Index. décimale : PER Périodiques Résumé : BACKGROUND: Social impairment is a defining feature of autism spectrum disorder (ASD) with no demonstrated effective pharmacologic treatments. The goal of this study was to evaluate efficacy, safety, and tolerability of oral N-acetylcysteine (NAC), an antioxidant whose function overlaps with proposed mechanisms of ASD pathophysiology, targeting core social impairment in youth with ASD. METHODS: This study was a 12-week randomized, double-blind, placebo-controlled trial of oral NAC in youth with ASD. Study participants were medically healthy youth age 4 to 12 years with ASD, weighing >/=15 kg, and judged to be moderately ill based on the Clinical Global Impressions Severity scale. The participants were randomized via computer to active drug or placebo in a 1:1 ratio, with the target dose of NAC being 60 mg/kg/day in three divided doses. The primary outcome measure of efficacy was the Clinical Global Impressions Improvement (CGI-I) scale anchored to core social impairment. To investigate the impact of NAC on oxidative stress markers in peripheral blood, venous blood samples were collected at screen and week 12. RESULTS: Thirty-one patients were enrolled (NAC = 16, placebo = 15). Three participants were lost to follow-up, and three left the trial due to adverse effects. The average daily dose of NAC at week 12 was 56.2 mg/kg (SD = 9.7) with dose ranging from 33.6 to 64.3 mg/kg. The frequency of adverse events was so low that comparisons between groups could not be conducted. At week 12, there was no statistically significant difference between the NAC and placebo groups on the CGI-I (p > 0.69) but the glutathione (GSH) level in blood was significantly higher in the NAC group (p < 0.05). The oxidative glutathione disulfide (GSSG) level increased in the NAC group, however only at a trend level of significance (p = 0.09). There was no significant difference between the NAC and placebo groups in the GSH/GSSG ratio, DNA strand break and oxidative damage, and blood homocysteine levels at week 12 (ps > 0.16). CONCLUSIONS: The results of this trial indicate that NAC treatment was well tolerated, had the expected effect of boosting GSH production, but had no significant impact on social impairment in youth with ASD. TRIAL REGISTRATION: Clinicaltrials.gov NCT00453180. En ligne : http://dx.doi.org/10.1186/s13229-016-0088-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] A randomized placebo-controlled pilot study of N-acetylcysteine in youth with autism spectrum disorder [Texte imprimé et/ou numérique] / L. K. WINK, Auteur ; R. ADAMS, Auteur ; Z. WANG, Auteur ; J. E. KLAUNIG, Auteur ; M. H. PLAWECKI, Auteur ; D. J. POSEY, Auteur ; C. J. MCDOUGLE, Auteur ; C. A. ERICKSON, Auteur . - 26p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 26p. Mots-clés : Acetylcysteine/pharmacology/therapeutic use  Administration, Oral  Autism Spectrum Disorder/drug therapy  Child  Child, Preschool  Comet Assay  DNA Damage/drug effects  Double-Blind Method  Drug Administration Schedule  Female  Follow-Up Studies  Free Radical Scavengers/pharmacology/therapeutic use  Glutathione/blood  Homocysteine/blood  Humans  Male  Oxidation-Reduction  Oxidative Stress/drug effects  Pilot Projects  Placebo Effect  Social Behavior  Autism  Autism spectrum disorder  N-acetylcysteine  Oxidative stress  Social impairment Index. décimale : PER Périodiques Résumé : BACKGROUND: Social impairment is a defining feature of autism spectrum disorder (ASD) with no demonstrated effective pharmacologic treatments. The goal of this study was to evaluate efficacy, safety, and tolerability of oral N-acetylcysteine (NAC), an antioxidant whose function overlaps with proposed mechanisms of ASD pathophysiology, targeting core social impairment in youth with ASD. METHODS: This study was a 12-week randomized, double-blind, placebo-controlled trial of oral NAC in youth with ASD. Study participants were medically healthy youth age 4 to 12 years with ASD, weighing >/=15 kg, and judged to be moderately ill based on the Clinical Global Impressions Severity scale. The participants were randomized via computer to active drug or placebo in a 1:1 ratio, with the target dose of NAC being 60 mg/kg/day in three divided doses. The primary outcome measure of efficacy was the Clinical Global Impressions Improvement (CGI-I) scale anchored to core social impairment. To investigate the impact of NAC on oxidative stress markers in peripheral blood, venous blood samples were collected at screen and week 12. RESULTS: Thirty-one patients were enrolled (NAC = 16, placebo = 15). Three participants were lost to follow-up, and three left the trial due to adverse effects. The average daily dose of NAC at week 12 was 56.2 mg/kg (SD = 9.7) with dose ranging from 33.6 to 64.3 mg/kg. The frequency of adverse events was so low that comparisons between groups could not be conducted. At week 12, there was no statistically significant difference between the NAC and placebo groups on the CGI-I (p > 0.69) but the glutathione (GSH) level in blood was significantly higher in the NAC group (p < 0.05). The oxidative glutathione disulfide (GSSG) level increased in the NAC group, however only at a trend level of significance (p = 0.09). There was no significant difference between the NAC and placebo groups in the GSH/GSSG ratio, DNA strand break and oxidative damage, and blood homocysteine levels at week 12 (ps > 0.16). CONCLUSIONS: The results of this trial indicate that NAC treatment was well tolerated, had the expected effect of boosting GSH production, but had no significant impact on social impairment in youth with ASD. TRIAL REGISTRATION: Clinicaltrials.gov NCT00453180. En ligne : http://dx.doi.org/10.1186/s13229-016-0088-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

A randomized, placebo-controlled trial of D-cycloserine for the enhancement of social skills training in autism spectrum disorders / N. F. MINSHAWI in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 2p. Titre : A randomized, placebo-controlled trial of D-cycloserine for the enhancement of social skills training in autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : N. F. MINSHAWI, Auteur ; L. K. WINK, Auteur ; R. SHAFFER, Auteur ; M. H. PLAWECKI, Auteur ; D. J. POSEY, Auteur ; H. LIU, Auteur ; S. HURWITZ, Auteur ; C. J. MCDOUGLE, Auteur ; N. B. SWIEZY, Auteur ; C. A. ERICKSON, Auteur Article en page(s) : 2p. Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/drug therapy/psychology/therapy  Behavior Therapy  Child  Child, Preschool  Cycloserine/adverse effects/therapeutic use  Double-Blind Method  Excitatory Amino Acid Agonists/adverse effects/therapeutic use  Female  Humans  Interpersonal Relations  Learning/drug effects  Male  Parents/psychology  Severity of Illness Index  Social Skills  Treatment Failure  Autism spectrum disorders  Social deficits  Social skills training  d-cycloserine Index. décimale : PER Périodiques Résumé : BACKGROUND: Researchers have demonstrated that d-cycloserine (DCS) can enhance the effects of behavioral interventions in adults with anxiety and enhances prosocial behavior in animal models of autism spectrum disorders (ASD). This study extended upon this background by combining DCS with behavioral social skills therapy in youth with ASD to assess its impact on the core social deficits of ASD. We hypothesized that DCS used in combination with social skills training would enhance the acquisition of social skills in children with ASD. METHODS: A 10-week, double-blind, placebo-controlled trial of DCS (50 mg) given 30 min prior to weekly group social skills training was conducted at two sites. Children with ASD were randomized to receive 10 weeks (10 doses) of DCS or placebo in a 1:1 ratio. RESULTS: No statistically significant difference attributable to drug treatment was observed in the change scores for the primary outcome measure, the Social Responsiveness Scale (SRS), total score (p = 0.45), or on secondary outcome measures. CONCLUSIONS: The results of this trial demonstrated no drug-related short-term improvement on the primary outcome measure, or any of the secondary outcome measures. However, an overall significant improvement in SRS total raw score was observed from baseline to end of treatment for the entire group of children with ASD. This suggests a need to further study the efficacy of the social skills training protocol. Limitations to the current study and areas for future research are discussed. TRIAL REGISTRATION: ClinicalTrials.govNCT01086475. En ligne : http://dx.doi.org/10.1186/s13229-015-0062-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] A randomized, placebo-controlled trial of D-cycloserine for the enhancement of social skills training in autism spectrum disorders [Texte imprimé et/ou numérique] / N. F. MINSHAWI, Auteur ; L. K. WINK, Auteur ; R. SHAFFER, Auteur ; M. H. PLAWECKI, Auteur ; D. J. POSEY, Auteur ; H. LIU, Auteur ; S. HURWITZ, Auteur ; C. J. MCDOUGLE, Auteur ; N. B. SWIEZY, Auteur ; C. A. ERICKSON, Auteur . - 2p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 2p. Mots-clés : Autism Spectrum Disorder/drug therapy/psychology/therapy  Behavior Therapy  Child  Child, Preschool  Cycloserine/adverse effects/therapeutic use  Double-Blind Method  Excitatory Amino Acid Agonists/adverse effects/therapeutic use  Female  Humans  Interpersonal Relations  Learning/drug effects  Male  Parents/psychology  Severity of Illness Index  Social Skills  Treatment Failure  Autism spectrum disorders  Social deficits  Social skills training  d-cycloserine Index. décimale : PER Périodiques Résumé : BACKGROUND: Researchers have demonstrated that d-cycloserine (DCS) can enhance the effects of behavioral interventions in adults with anxiety and enhances prosocial behavior in animal models of autism spectrum disorders (ASD). This study extended upon this background by combining DCS with behavioral social skills therapy in youth with ASD to assess its impact on the core social deficits of ASD. We hypothesized that DCS used in combination with social skills training would enhance the acquisition of social skills in children with ASD. METHODS: A 10-week, double-blind, placebo-controlled trial of DCS (50 mg) given 30 min prior to weekly group social skills training was conducted at two sites. Children with ASD were randomized to receive 10 weeks (10 doses) of DCS or placebo in a 1:1 ratio. RESULTS: No statistically significant difference attributable to drug treatment was observed in the change scores for the primary outcome measure, the Social Responsiveness Scale (SRS), total score (p = 0.45), or on secondary outcome measures. CONCLUSIONS: The results of this trial demonstrated no drug-related short-term improvement on the primary outcome measure, or any of the secondary outcome measures. However, an overall significant improvement in SRS total raw score was observed from baseline to end of treatment for the entire group of children with ASD. This suggests a need to further study the efficacy of the social skills training protocol. Limitations to the current study and areas for future research are discussed. TRIAL REGISTRATION: ClinicalTrials.govNCT01086475. En ligne : http://dx.doi.org/10.1186/s13229-015-0062-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

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