scholarly journals Phase-IIa randomized, double-blind, sham-controlled, parallel group trial on anodal transcranial direct current stimulation (tDCS) over the left and right tempo-parietal junction in autism spectrum disorder—StimAT: study protocol for a clinical trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Christina Luckhardt ◽  
Magdalena Schütz ◽  
Andreas Mühlherr ◽  
Hannah Mössinger ◽  
Sara Boxhoorn ◽  
...  
Keyword(s):  
Cognitive Abilities ◽  
Social Cognitive ◽  
Autism Spectrum ◽  
Social Responsiveness ◽  
Post Intervention ◽  
Double Blind ◽  
Parallel Group ◽  
Promising Treatment ◽  
Core Symptoms

Abstract Background Autism spectrum disorder (ASD) is characterized by impaired social communication and interaction, and stereotyped, repetitive behaviour and sensory interests. To date, there is no effective medication that can improve social communication and interaction in ASD, and effect sizes of behaviour-based psychotherapy remain in the low to medium range. Consequently, there is a clear need for new treatment options. ASD is associated with altered activation and connectivity patterns in brain areas which process social information. Transcranial direct current stimulation (tDCS) is a technique that applies a weak electrical current to the brain in order to modulate neural excitability and alter connectivity. Combined with specific cognitive tasks, it allows to facilitate and consolidate the respective training effects. Therefore, application of tDCS in brain areas relevant to social cognition in combination with a specific cognitive training is a promising treatment approach for ASD. Methods A phase-IIa pilot randomized, double-blind, sham-controlled, parallel-group clinical study is presented, which aims at investigating if 10 days of 20-min multi-channel tDCS stimulation of the bilateral tempo-parietal junction (TPJ) at 2.0 mA in combination with a computer-based cognitive training on perspective taking, intention and emotion understanding, can improve social cognitive abilities in children and adolescents with ASD. The main objectives are to describe the change in parent-rated social responsiveness from baseline (within 1 week before first stimulation) to post-intervention (within 7 days after last stimulation) and to monitor safety and tolerability of the intervention. Secondary objectives include the evaluation of change in parent-rated social responsiveness at follow-up (4 weeks after end of intervention), change in other ASD core symptoms and psychopathology, social cognitive abilities and neural functioning post-intervention and at follow-up in order to explore underlying neural and cognitive mechanisms. Discussion If shown, positive results regarding change in parent-rated social cognition and favourable safety and tolerability of the intervention will confirm tDCS as a promising treatment for ASD core-symptoms. This may be a first step in establishing a new and cost-efficient intervention for individuals with ASD. Trial registration The trial is registered with the German Clinical Trials Register (DRKS), DRKS00014732. Registered on 15 August 2018. Protocol version This study protocol refers to protocol version 1.2 from 24 May 2019.

scholarly journals Oxytocin-induced increase in N,N-dimethylglycine and time course of changes in oxytocin efficacy for autism social core symptoms

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yasuhiko Kato ◽  
Hitoshi Kuwabara ◽  
Takashi Okada ◽  
Toshio Munesue ◽  
Seico Benner ◽  
...  
Keyword(s):  
Effect Size ◽  
Neural Plasticity ◽  
Time Course ◽  
Molecular Mechanisms ◽  
Controlled Trial ◽  
Autism Spectrum ◽  
Medium Effect ◽  
Double Blind ◽  
Parallel Group ◽  
Core Symptoms

Abstract Background Oxytocin is expected as a novel therapeutic agent for autism spectrum disorder (ASD) core symptoms. However, previous results on the efficacy of repeated administrations of oxytocin are controversial. Recently, we reported time-course changes in the efficacy of the neuropeptide underlying the controversial effects of repeated administration; however, the underlying mechanisms remained unknown. Methods The current study explored metabolites representing the molecular mechanisms of oxytocin’s efficacy using high-throughput metabolomics analysis on plasma collected before and after 6-week repeated intranasal administration of oxytocin (48 IU/day) or placebo in adult males with ASD (N = 106) who participated in a multi-center, parallel-group, double-blind, placebo-controlled, randomized controlled trial. Results Among the 35 metabolites measured, a significant increase in N,N-dimethylglycine was detected in the subjects administered oxytocin compared with those given placebo at a medium effect size (false discovery rate (FDR) corrected P = 0.043, d = 0.74, N = 83). Furthermore, subgroup analyses of the participants displaying a prominent time-course change in oxytocin efficacy revealed a significant effect of oxytocin on N,N-dimethylglycine levels with a large effect size (PFDR = 0.004, d = 1.13, N = 60). The increase in N,N-dimethylglycine was significantly correlated with oxytocin-induced clinical changes, assessed as changes in quantifiable characteristics of autistic facial expression, including both of improvements between baseline and 2 weeks (PFDR = 0.006, r = − 0.485, N = 43) and deteriorations between 2 and 4 weeks (PFDR = 0.032, r = 0.415, N = 37). Limitations The metabolites changes caused by oxytocin administration were quantified using peripheral blood and therefore may not directly reflect central nervous system changes. Conclusion Our findings demonstrate an association of N,N-dimethylglycine upregulation with the time-course change in the efficacy of oxytocin on autistic social deficits. Furthermore, the current findings support the involvement of the N-methyl-D-aspartate receptor and neural plasticity to the time-course change in oxytocin’s efficacy. Trial registration: A multi-center, parallel-group, placebo-controlled, double-blind, confirmatory trial of intranasal oxytocin in participants with autism spectrum disorders (the date registered: 30 October 2014; UMIN Clinical Trials Registry: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017703) (UMIN000015264).

Oxytocin-Induced Increase in N,N-dimethylglycine and Time-Course of Changes in Oxytocin Efficacy for Autism Social Core Symptoms

2020 ◽  
Author(s):  
Yasuhiko Kato ◽  
Hitoshi Kuwabara ◽  
Takashi Okada ◽  
Toshio Munesue ◽  
Seico Benner ◽  
...  
Keyword(s):  
Effect Size ◽  
Neural Plasticity ◽  
Time Course ◽  
Molecular Mechanisms ◽  
Controlled Trial ◽  
Autism Spectrum ◽  
Medium Effect ◽  
Double Blind ◽  
Parallel Group ◽  
Core Symptoms

Abstract Background: Oxytocin is expected as a novel therapeutic agent for autism spectrum disorder (ASD) core symptoms. However, previous results on the efficacy of repeated administrations of oxytocin are controversial. Recently, we reported time-course changes in the efficacy of the neuropeptide underlying the controversial effects of repeated administration; however, the underlying mechanisms remained unknown. Methods: The current study explored metabolites representing the molecular mechanisms of oxytocin's efficacy using high-throughput metabolomics analysis on plasma collected before and after 6 week repeated intranasal administration of oxytocin (48 IU/day) or placebo in adult males with ASD (N=106) who participated in a multi-center, parallel-group, double-blind, placebo-controlled, randomized controlled trial.Results: Among the 35 metabolites measured, a significant increase in N,N-dimethylglycine was detected in the subjects administered oxytocin compared with those given placebo at a medium effect size (False discovery rate (FDR) corrected P=0.043, d=0.74, N=83). Furthermore, subgroup analyses of the participants displaying a prominent time-course change in oxytocin efficacy revealed a significant effect of oxytocin on N,N-dimethylglycine levels with a large effect size (PFDR=0.004, d=1.13, N=60). The increase in N,N-dimethylglycine was significantly correlated with oxytocin-induced clinical changes, assessed as changes in quantifiable characteristics of autistic facial expression, including both of improvements between baseline and 2 weeks (PFDR=0.006, r=-0.485, N=43) and deteriorations between 2 and 4 weeks (PFDR=0.032, r=0.415, N=37).Limitations: The metabolites changes caused by oxytocin administration were quantified using peripheral blood, and therefore may not directly reflect central nervous system changes. Conclusion: Our findings demonstrate an association of N,N-dimethylglycine upregulation with the time-course change in the efficacy of oxytocin on autistic social deficits. Furthermore, the current findings support the involvement of the N-Methyl-D-Aspartate receptor and neural plasticity to the time-course change in oxytocin’s efficacy.Trial registration: A multicenter, parallel group, placebo-controlled, double blind, confirmatory trial of intranasal oxytocin in participants with autism spectrum disorders. (The date registered: 30th Oct 2020; UMIN Clinical Trials Registry: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017703) (UMIN000015264)

scholarly journals Subgroups of Children with Autism Spectrum Disorder without Intellectual Disability: A Longitudinal Examination of Executive and Socio-Adaptive Behaviors in Adolescence

2021 ◽  
Vol 10 (10) ◽  
pp. 2220
Author(s):  
Rocio Rosello ◽  
Carmen Berenguer ◽  
Jose Martinez-Raga ◽  
Ana Miranda ◽  
Samuele Cortese
Keyword(s):  
Intellectual Disability ◽  
Social Cognitive ◽  
Autism Spectrum ◽  
Social Impairment ◽  
Care Plans ◽  
The Social ◽  
Patterns Of Behavior ◽  
Living Skills ◽  
Core Symptoms

Within the autistic spectrum, there is remarkable variability in the etiology, presentation, and treatment response. This prospective study was designed to identify, through cluster analysis, subgroups of individuals with ASD without intellectual disability (ID) based on the severity of the core symptoms in childhood. The secondary aim was to explore whether these subgroups and a group with typical development (TD) differ in cognitive, adaptive, and social aspects measured in adolescence. The sample at baseline was comprised of 52 children with ASD without ID and 37 children with TD, aged 7–11. Among the ASD group, three clusters were identified. Cluster 1 (40%), ‘high severity’, presented high symptom severity on the DSM-5 criteria and the Social Communication Questionnaire. Cluster 2 (34%) showed ‘moderate severity’ on most of the scores. Cluster 3 (25%) corresponded to ‘low severity’, showing moderate social impairment and low restrictive, repetitive patterns of behavior, interests and activities. At 5-year follow-up, 45 adolescents with ASD without ID and 27 adolescents with TD were assessed. All clusters had significantly more difficulties in EF, ToM, socialization and adaptive behavior compared to TD. Social and adaptive trajectories between the ASD subgroups were relatively different; Cluster 3 showed poorer socialization and daily living skills than the other two subgroups. These findings highlight the importance of fully assessing social, cognitive, and adaptive profiles to develop care plans tailored to specific needs.

A Case Study: Unique Challenges of an Adolescent Female With Autism Spectrum Disorder

2020 ◽  
Vol 5 (1) ◽  
pp. 314-325
Author(s):  
Kimberly F. Frazier ◽  
Jessica Collier ◽  
Rachel Glade
Keyword(s):  
Autism Spectrum Disorder ◽  
Cognitive Abilities ◽  
Social Cognitive ◽  
Social Performance ◽  
Management Strategies ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Self Management ◽  
Adolescent Female ◽  
Social Thinking

Background The aim of this study was to determine the clinical efficacy of combining self-management strategies and a social thinking approach to address the social performance and executive function of an adolescent female with autism spectrum disorder. Method This research examined the effects of a social knowledge training program, “Think Social,” as well as strategies to improve higher order cognitive abilities. Results and Conclusion Although quantitative improvement was not found, several qualitative gains in behavior were noted for the participants of this study, suggesting a benefit from using structured environmental cues of self-management strategies, as well as improved social understanding through social cognitive training.

A Double-Blind Comparison of 0.25% and 0.05% Desoxymethasone, 0.1% Betamethasone Valerate and 1% Hydrocortisone Creams in the Treatment of Eczema

1987 ◽  
Vol 15 (3) ◽  
pp. 160-166 ◽  
Author(s):  
R. E. Ashton ◽  
M. Catterall ◽  
N. Morley ◽  
G. Fairris ◽  
D. N. Joseph
Keyword(s):  
Adverse Effects ◽  
Physical Properties ◽  
Effective Treatment ◽  
The Other ◽  
Betamethasone Valerate ◽  
Clinical Parameters ◽  
Double Blind ◽  
Parallel Group ◽  
Blind Comparison

The efficacy and acceptability of 0.25% and 0.05% desoxymethasone, 0.1% betamethasone valerate and 1% hydrocortisone creams were compared in patients with eczema. A double-blind parallel group multi-centre design was employed in which 96 patients were recruited by four centres. Patients used one cream for a 3-week period and follow-up assessment visits were made at weekly intervals. Efficacy variables were: erythema/redness, scaling, itching and extent of area affected. These variables were assessed by both the investigator and the patient. The 0.25% desoxymethasone was the most effective treatment, producing the greatest degree of improvement in all clinical parameters, hydrocortisone was the least effective and 0.05% desoxymethasone was of intermediate effectiveness. The 0.1% betamethasone produced similar results to 0.25% desoxymethasone for half the assessments; for the other half the results were similar to 0.05% desoxymethasone. No adverse effects were reported during the study. The results are discussed in terms of physical properties of the vehicles and corticosteroid potency.

Evaluating the effects of a yoga-based program integrated with third-wave cognitive behavioral therapy components on self-regulation in children on the autism spectrum: A pilot randomized controlled trial

Autism ◽  
2020 ◽  
pp. 136236132097484
Author(s):  
Radhika Tanksale ◽  
Kate Sofronoff ◽  
Jeanie Sheffield ◽  
John Gilmour
Keyword(s):  
Confidence Interval ◽  
Executive Control ◽  
Sleep Problems ◽  
Behavioral Therapy ◽  
Self Regulation ◽  
Autism Spectrum ◽  
Third Wave ◽  
Post Intervention ◽  
Yoga Group

Research using mind–body practices in autism is limited but suggests a trend for ruminative reduction and improved behavioral–emotional outcomes. Following random assignment ( N = 67), effects of a weekly six-session pilot yoga-based group program combined with third-wave cognitive behavioral therapy elements on self-regulation for children on the autism spectrum (aged 8–12 years) was assessed. The primary outcome was executive functions. Secondary outcomes were sleep, anxiety, and emotion awareness. After attrition, assessment results from participants in the intervention ( n = 31) and the waitlist conditions ( n = 30) completed at baseline, post-intervention, and 6-week follow-up were evaluated. For the intervention group, the between-group mean score differences suggest a decrease in parent-reported global executive difficulties from baseline to post-intervention (−2.61; 95% confidence interval −5.13 to −0.09, p  = 0.047, d = −0.39) and baseline to follow-up (−4.17; 95% confidence interval −6.72 to −1.62, p = 0.017, d = −0.59) with small-to-medium effect sizes. Small-to-medium effects were found for a few parent-reported children’s sleep issues, child-reported aspects of emotion awareness, and performance anxiety. Non-significant findings are discussed in this article. Preliminary findings suggest mixed results and should be interpreted cautiously. The yoga-informed program may complement existing treatments and will benefit from ongoing evaluation. Lay abstract Children on the autism spectrum may experience difficulties with the regulation of attention, thoughts, emotions, and behavior, understanding, and expressing their emotions appropriately, as well as anxiety, and sleep. In autism research, contemplative practices that work through both body and mind have shown tentatively promising results. However, there are limited studies on this topic, and the use of yoga to facilitate executive control has not been researched yet. The Incredible Explorers (6-week program), a yoga-informed intervention program for children (8–12 years), was developed to understand whether, for children on the autism spectrum, the training could improve the ability to self-regulate, reduce anxiety and sleep problems, and increase awareness of emotions. In our sample, 61 children with one of their parents completed the program. Half of the group received the intervention, and the other half had to wait until the yoga group completed their trial. The participants were asked to give their feedback immediately after program completion and at 6-week follow-up. Compared to the group that was waiting to receive the intervention, parents in the yoga group reported significant gains for their children in regulating their overall executive control immediately after the session and again at follow-up. The parents reported a reduction in some of the sleep problems post-treatment. Children indicated an improved ability to communicate their feelings and willingness to analyze their emotions post-intervention. However, the study had several shortcomings and given that this was the first trial of the program, the results need to be interpreted with caution. Further research is recommended.

scholarly journals Efficacy and safety of memantine in children with autism spectrum disorder: Results from three phase 2 multicenter studies

Autism ◽  
2019 ◽  
Vol 23 (8) ◽  
pp. 2096-2111 ◽  
Author(s):  
Antonio Y Hardan ◽  
Robert L Hendren ◽  
Michael G Aman ◽  
Adelaide Robb ◽  
Raun D Melmed ◽  
...  
Keyword(s):  
Extended Release ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Social Responsiveness Scale ◽  
Social Responsiveness ◽  
Phase 2 ◽  
Open Label ◽  
Double Blind ◽  
Three Phase ◽  
Open Label Trial

Three phase 2 trials were conducted to assess the efficacy and long-term safety of weight-based memantine extended release (ER) treatment in children with autism spectrum disorder. MEM-MD-91, a 50-week open-label trial, identified memantine extended-release treatment responders for enrollment into MEM-MD-68, a 12-week randomized, double-blind, placebo-controlled withdrawal trial. MEM-MD-69 was an open-label extension trial in which participants from MEM-MD-68, MEM-MD-91, and open-label trial MEM-MD-67 were treated ⩽48 weeks with memantine extended release. In MEM-MD-91, 517 (59.6%) participants were confirmed Social Responsiveness Scale responders at week 12; mean Social Responsiveness Scale total raw scores improved two to three times a minimal clinically important difference of 10 points. In MEM-MD-68, there was no difference between memantine and placebo on the primary efficacy parameter, the proportion of patients with a loss of therapeutic response (defined as ⩾10-point increase from baseline in Social Responsiveness Scale total raw score). MEM-MD-69 exploratory analyses revealed mean standard deviation improvement in Social Responsiveness Scale total raw score of 32.4 (26.4) from baseline of the first lead-in study. No new safety concerns were evident. While the a priori–defined efficacy results of the double-blind trial were not achieved, the considerable improvements in mean Social Responsiveness Scale scores from baseline in the open-label trials were presumed to be clinically important.

scholarly journals Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism

2017 ◽  
Vol 114 (30) ◽  
pp. 8119-8124 ◽  
Author(s):  
Karen J. Parker ◽  
Ozge Oztan ◽  
Robin A. Libove ◽  
Raena D. Sumiyoshi ◽  
Lisa P. Jackson ◽  
...  
Keyword(s):  
Social Functioning ◽  
Placebo Treatment ◽  
Primary Outcome Measure ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Social Responsiveness ◽  
Social Deficits ◽  
Double Blind ◽  
Children With Asd ◽  
Social Abilities

Autism spectrum disorder (ASD) is characterized by core social deficits. Prognosis is poor, in part, because existing medications target only associated ASD features. Emerging evidence suggests that the neuropeptide oxytocin (OXT) may be a blood-based biomarker of social functioning and a possible treatment for ASD. However, prior OXT treatment trials have produced equivocal results, perhaps because of variability in patients’ underlying neuropeptide biology, but this hypothesis has not been tested. Using a double-blind, randomized, placebo-controlled, parallel design, we tested the efficacy and tolerability of 4-wk intranasal OXT treatment (24 International Units, twice daily) in 32 children with ASD, aged 6–12 y. When pretreatment neuropeptide measures were included in the statistical model, OXT compared with placebo treatment significantly enhanced social abilities in children with ASD [as measured by the trial’s primary outcome measure, the Social Responsiveness Scale (SRS)]. Importantly, pretreatment blood OXT concentrations also predicted treatment response, such that individuals with the lowest pretreatment OXT concentrations showed the greatest social improvement. OXT was well tolerated, and its effects were specific to social functioning, with no observed decrease in repetitive behaviors or anxiety. Finally, as with many trials, some placebo-treated participants showed improvement on the SRS. This enhanced social functioning was mirrored by a posttreatment increase in their blood OXT concentrations, suggesting that increased endogenous OXT secretion may underlie this improvement. These findings indicate that OXT treatment enhances social abilities in children with ASD and that individuals with pretreatment OXT signaling deficits may stand to benefit the most from OXT treatment.

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