Randomized Double-blind Clinical Trial With L.Reuteri Supplementation in Children With Autism Spectrum Disorder
Condition: Autism Spectrum Disorder
MeSH terms: Autism Spectrum Disorder
Study type: Interventional

Summary: 
      The aim of this study is to assess the effects of a 6-months probiotic supplementation on
      behavioral profiles, microbiota and metabolic profiles, inflammatory biomarkers,
      gastrointestinal disturbances, in children with Autism Spectrum Disorders (ASD) with or
      without GI symptoms.
    

Detailed description: 
      Autism Spectrum Disorder (ASD) is a condition that includes social deficits, repetitive
      behaviors and language difficulties; its prevalence continues to increase worldwide, however,
      there are no medication for the core symptoms of this disorder. In addition to these core
      symptoms, children with ASD are 3.5 times more likely to suffer from gastrointestinal issues
      than children without developmental disorders. Moreover, GI problems have been associated
      with changes in the microbial communities inhabiting the gut of ASD individuals.

      Studies in animal models have suggested that the gut microbes can modulate central nervous
      system-driven behaviors.

      In 2019, a research group (Buffington et al.) found that a specific strain (L. Reuteri PTA)
      rescues the deficit in social interaction-induced VTA plasticity in ASD mouse, enhancing the
      salience and rewarding value of social stimuli.

      These data support the idea that microbial therapies could ameliorate specific endophenotypes
      associates with ASD.

      Aim of the study The aim of this pilot study is to determine the possible effects of
      supplementation with a specific probiotic strain (L. Reuteri ATCC PTA 6475) in ASD children
      on the core deficits of the disorder, the social behavior. A secondary aim is to evaluate the
      effects of probiotic supplementation on specific GI symptoms, and repetitive, dysfunctional
      behaviors, widely described in ASD children. Finally, the investigators will evaluate gut
      microbiota (fecal and salivary samples) and metabolomics (urinary samples) profiles
      differences before and after the supplementation.

      Methods and participants Double blind randomized, placebo-controlled trial, with a
      nutritional supplement, with two parallel arms, an allocation ratio of 1:1, and a superiority
      framework.

      The investigators aim to enroll 80 patients. A detailed informed consent will be given and
      and both parents will sign it before the start of the data collection.

      The participants, after a first evaluation, will be divided into 2 groups; each arm will be
      blind randomized 1:1 to regular diet with a specific probiotic strain (L. Reuteri ATCC PTA
      6475) or with placebo for 6 months.

      After randomization the investigators will explain how to take the product and the first dose
      will be administered.

      During the study the child is not allowed to take other probiotics. The type of
      neurologic/rehabilitation therapy ongoing at T0 cannot be changed until the study is
      finished.

      Study Product Test product chewable tablets: 1x108 CFU Lactobacillus reuteri DSM 17938 +
      1x108 CFU Lactobacillus reuteri ATCC PTA 6475 (together 2x108 CFU) Placebo chewable caps:
      identical in shape and taste to the test product without the Lactobacillus reuteri components
      Both study products are delivered in identical containers and labelled as XXX. Dosing: Two
      tablets/cps once a day.

      Assessment

      At the time of enrollment, each participant will undergo a comprehensive neuropsychological
      and biochemical evaluation, in order to establish the baseline of the primary and secondary
      outcome measures. A detailed Case Record Forms (CRF) containing all data pertinent to the
      study will be prepared.

      At T0 the investigators will also collect blood, urinary salivary and fecal sample from each
      participant in order to perform biochemical, microbiological and metabolomics evaluation. The
      parents have to fill out questionnaire about dietary habits in a 5 day-diary.

      After three months from the enrollment (T1), each child will undergo a second evaluation with
      some clinical and biological measures.

      At the end of the study, six months from baseline, the investigators will perform another
      complete assessment through the same clinical, biochemical and neuropsychological evaluation
      performed at T0, to evaluate the possible changes in (1) autism symptoms severity; (2)
      affective and behavioral comorbid symptoms; (3) GI symptoms; (4) plasmatic, urinary and fecal
      biomarkers related to abnormal intestinal/inflammatory function. At T2, urinary salivary, and
      fecal sample will be also collected from each participant in order to perform microbiological
      and metabolomics evaluation.

      All children recruited will undergo the evaluation at Child Neurology and Psychiatry unit,
      Policlinico Tor Vergata, Rome, Italy.
    

Intervention name(s): L.Reuteri; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): daily supplementation with two tablet for six months; daily supplementation with two tablet for six months
Other intervention name(s): Gastrus
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: double-blind randomized, parallel-group, placebo-controlled study
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Probiotic; Gut-Brain axis; L. Reuteri; Social Behavior; Microbiome; Metabolome; Inflammatory Profile; Gastrointestinal Symptoms