Randomized Double-blind Clinical Trial With L.Reuteri Supplementation in Children With Autism Spectrum Disorder
- Conditions
- Autism Spectrum Disorder
- Interventions
- Dietary Supplement: PlaceboDietary Supplement: L.Reuteri
- Registration Number
- NCT04293783
- Lead Sponsor
- University of Rome Tor Vergata
- Brief 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 43
- Autism Spectrum Disorder (DSM-5 criteria diagnosis)
- neurological syndromes (that explain autism symptoms)
- coeliac disease
- other organic GI disorder
- special diet.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo two tablet by mouth 1 times per day L.Reuteri L.Reuteri Lactobacillus reuteri DSM 17938 + Lactobacillus reuteri ATCC PTA 6475 two tablet by mouth 1 time per day
- Primary Outcome Measures
Name Time Method Changes in Microbiome Profile 3 months and 6 months Characterization of the fecal and salivary microbiota by using a metagenomic approach (amplification and sequencing of a portion of the bacterial 16S rRNA) gene. A special focus is to evaluate if there is dysbiosis, if the supplementation rescues the dysbiosis and if these changes are correlated with the gastrointestinal and behavioral symptoms
Changes in severity level of ASD symptomatology 6 months Delta of scores at Autism Diagnostic Observation Schedule-2
- Secondary Outcome Measures
Name Time Method Changes in Parental Stress 3 months and 6 months Delta of scores at PSI (Parenting Stress Index)
Changes in ASD symptomatology: repetitive behaviors 3 months and 6 months Delta of scores at RBS-R (Repetitive Behavior Scale-Revised), a 43 item scale. Higher scores are related to greater severity of symptoms
Changes in Adaptive Functioning 6 months Delta of scores at Adaptive Behavior Assessment System-II
Changes in Behavioral Profiles 3 months and 6 months Delta of scores at CBCL (Child Behavior CheckList)
Changes in GI symptoms 3 months and 6 months Delta of scores at GSRS (Gastrointestinal Symptoms Rating Scale). Higher scores are related to greater severity of symptoms
Changes in ASD symptomatology: problematic behaviors 3 months and 6 months Delta of scores at ABC (Aberrant Behavior Checklist), a 58 item scale. Higher scores are related to greater severity of symptoms
Changes in global ASD symptomatology 3 months and 6 months Delta of scores at SRS (Social Responsiveness Scale). Higher scores are related to greater severity of symptoms
Changes in Metabolomic Profile 6 months Urinary samples collected for NMR analysis. Metabolomics profiles will be directed at biochemical processes such as neurotransmitter metabolism, gastrointestinal alterations or dysbiosis, and mitochondrial dysfunction). Furthermore, the effect of probiotic administration on the metabolome will be investigated.
Changes in Inflammatory Profile 6 months Blood sample collected to evaluate changes in inflammatory profile (zonulin, IL-17 profile)
Trial Locations
- Locations (2)
University of Bari
🇮🇹Bari, BA, Italy
University of Rome Tor Vergata
🇮🇹Rome, RM, Italy