Dataset Information

Probiotics and oxytocin nasal spray as neuro-social-behavioral interventions for patients with autism spectrum disorders: a pilot randomized controlled trial protocol.

ABSTRACT: Background:Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in social interaction and communication. Oxytocin (OXT), as a neuropeptide, plays a role in emotional and social behaviors. Lactobacillus reuteri (L. reuteri) supplementation led to an OXT-dependent behavioral improvement in ASD mouse models. Despite some promising results from animal studies, little is known about the efficacy of supplementation with L. reuteri, alone or with exogenous OXT therapy, on social-behavioral functions in ASD patients. This paper presents a protocol for a pilot randomized controlled trial to evaluate the feasibility of conducting a full trial comparing oral supplementation of L. reuteri probiotics and intranasal OXT spray to placebo on the effect of social and behavioral functions in ASD patients. The study will also capture preliminary estimates of the efficacy of the proposed interventions in ASD patients. Methods:This pilot trial is a two-staged, randomized, double-blind, placebo-controlled, parallel-group study. Throughout the study (0-24 weeks), 60 patients with ASD will be randomly assigned to receive either oral L. reuteri probiotics or placebo. In the second study stage (13-24 weeks), all participants will receive intranasal OXT spray. As primary outcomes, serum OXT levels will be assayed and social behaviors will be assessed via the Autism Behavior Checklist and the Social Responsiveness Scale which are validated questionnaires, an objective emotional facial matching test, and a new video-based eye-tracking test. Secondary outcomes include the GI-severity-index and Bristol Stool Chart to assess GI function and gut microbiome/short-chain fatty acids. All the outcomes will be assessed at baseline and weeks 12 and 24. Discussion:This pilot study will provide important information on the feasibility of recruitment, blinding and concealment, treatment administration, tolerability and adherence, specimen collection, outcome assessment, potential adverse effects, and the preliminary efficacy on both primary and secondary outcomes. If successful, this pilot study will inform a larger randomized controlled trial fully powered to examine the efficacies of oral L. reuteri probiotics and/or intranasal OXT spray on social-behavioral improvement in ASD patients. Trial registration:ClinicalTrials.gov, NCT03337035. Registered 8 November 2017.

SUBMITTER: Kong XJ

PROVIDER: S-EPMC7017510 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Probiotics and oxytocin nasal spray as neuro-social-behavioral interventions for patients with autism spectrum disorders: a pilot randomized controlled trial protocol.

Kong Xue-Jun XJ Liu Jun J Li Jing J Kwong Kenneth K Koh Madelyn M Sukijthamapan Piyawat P Guo Jason J JJ Sun Zhenyu Jim ZJ Song Yiqing Y

Pilot and feasibility studies 20200212

<h4>Background</h4>Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in social interaction and communication. Oxytocin (OXT), as a neuropeptide, plays a role in emotional and social behaviors. <i>Lactobacillus reuteri</i> (<i>L. reuteri</i>) supplementation led to an OXT-dependent behavioral improvement in ASD mouse models. Despite some promising results from animal studies, little is known about the efficacy of supplementation with <i>L. reuter ...[more]

PMID: 32082606

Similar Datasets

Project description:UnlabelledApproximately half of autism spectrum disorder (ASD) individuals suffer from comorbid intellectual disabilities (IDs). Oxytocin (OXT) receptors are highly expressed in temporal lobe structures and are likely to play a modulatory role in excitatory/inhibitory balance, at least based on animal model findings. Thus, it is feasible that in the highly representative group of Kanner-type ASD subjects, OXT could have a beneficial effect on social communication and social interaction. The aim of this pilot study is to investigate the feasibility and adverse events, such as epilepsy, of the long-term administration of intranasal OXT for adolescent and adult ASD subjects with ID because such patients frequently have seizures. We also addressed the question on how to scale the OXT effects to the core symptoms of social deficits because of the relative difficulty in obtaining objective measurements. Twenty-nine males (aged 15-40 years old) participated in a randomized, double-blind, and placebo-controlled crossover study (each for 8 weeks) with OXT (16 IU/day). Except for seizures experienced by one participant, other serious adverse events did not occur. The primary and secondary outcomes measured using the Childhood Autism Rating Scale and several standard scales, respectively, revealed no difference between the OXT and placebo groups. Instead, in an exploratory analysis, the social interactions observed in the play sessions or in daily life were significantly more frequent in the initial half period in the OXT-first arm of the crossover trial. There were also significant correlations between the plasma OXT concentration and subscale scores for irritability on the Aberrant Behavior Checklist. In conclusion, this pilot study demonstrates that long-term administration of intranasal OXT is tolerable in a representative cohort of ASD individuals with ID and suggests that future multicenter trials of OXT are warranted and should include measurements of reciprocal social interactions based on daily life under closer surveillance for epilepsy.Trial registrationUMIN000007250.

Project description:BackgroundExperimental studies and small clinical trials have suggested that treatment with intranasal oxytocin may reduce social impairment in persons with autism spectrum disorder. Oxytocin has been administered in clinical practice to many children with autism spectrum disorder.MethodsWe conducted a 24-week, placebo-controlled phase 2 trial of intranasal oxytocin therapy in children and adolescents 3 to 17 years of age with autism spectrum disorder. Participants were randomly assigned in a 1:1 ratio, with stratification according to age and verbal fluency, to receive oxytocin or placebo, administered intranasally, with a total target dose of 48 international units daily. The primary outcome was the least-squares mean change from baseline on the Aberrant Behavior Checklist modified Social Withdrawal subscale (ABC-mSW), which includes 13 items (scores range from 0 to 39, with higher scores indicating less social interaction). Secondary outcomes included two additional measures of social function and an abbreviated measure of IQ.ResultsOf the 355 children and adolescents who underwent screening, 290 were enrolled. A total of 146 participants were assigned to the oxytocin group and 144 to the placebo group; 139 and 138 participants, respectively, completed both the baseline and at least one postbaseline ABC-mSW assessments and were included in the modified intention-to-treat analyses. The least-squares mean change from baseline in the ABC-mSW score (primary outcome) was -3.7 in the oxytocin group and -3.5 in the placebo group (least-squares mean difference, -0.2; 95% confidence interval, -1.5 to 1.0; P = 0.61). Secondary outcomes generally did not differ between the trial groups. The incidence and severity of adverse events were similar in the two groups.ConclusionsThis placebo-controlled trial of intranasal oxytocin therapy in children and adolescents with autism spectrum disorder showed no significant between-group differences in the least-squares mean change from baseline on measures of social or cognitive functioning over a period of 24 weeks. (Funded by the National Institute of Child Health and Human Development; SOARS-B ClinicalTrials.gov number, NCT01944046.).

Project description:Fetal neuroinflammation and prenatal stress (PS) may contribute to lifelong neurological disabilities. Astrocytes and microglia, among the brain's non-neuronal "glia" cell populations, play a pivotal role in neurodevelopment and predisposition to and initiation of disease throughout lifespan. One of the most common neurodevelopmental disorders manifesting between 1-4 years of age is the autism spectrum disorder (ASD). A pathological glial-neuronal interplay is thought to increase the risk for clinical manifestation of ASD in at-risk children, but the mechanisms remain poorly understood, and integrative, multi-scale models are needed. We propose a model that integrates the data across the scales of physiological organization, from genome to phenotype, and provides a foundation to explain the disparate findings on the genomic level. We hypothesize that via gene-environment interactions, fetal neuroinflammation and PS may reprogram glial immunometabolic phenotypes that impact neurodevelopment and neurobehavior. Drawing on genomic data from the recently published series of ovine and rodent glial transcriptome analyses with fetuses exposed to neuroinflammation or PS, we conducted an analysis on the Simons Foundation Autism Research Initiative (SFARI) Gene database. We confirmed 21 gene hits. Using unsupervised statistical network analysis, we then identified six clusters of probable protein-protein interactions mapping onto the immunometabolic and stress response networks and epigenetic memory. These findings support our hypothesis. We discuss the implications for ASD etiology, early detection, and novel therapeutic approaches. We conclude with delineation of the next steps to verify our model on the individual gene level in an assumption-free manner. The proposed model is of interest for the multidisciplinary community of stakeholders engaged in ASD research, the development of novel pharmacological and non-pharmacological treatments, early prevention, and detection as well as for policy makers.

Dataset Information

Probiotics and oxytocin nasal spray as neuro-social-behavioral interventions for patients with autism spectrum disorders: a pilot randomized controlled trial protocol.

Publications

Probiotics and oxytocin nasal spray as neuro-social-behavioral interventions for patients with autism spectrum disorders: a pilot randomized controlled trial protocol.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets