Probiotics for Autism Spectrum Disorders: a Randomized Controlled Trial (The PASD Study)

Overview

Autism spectrum disorders (ASD) are a group of severe neurodevelopmental conditions characterized by impaired communication and social interaction, as well as repetitive/stereotyped behaviors deriving from a combination of genetic and environmental factors. The ASD diagnosis rates increased dramatically over the past number of decades. The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) describes a worldwide prevalence of approximately 1%. The prevalence of ASD is 1 in 59 individuals in the US reported by the Centers for Disease Control and Prevention. According to the latest data from the Italian National Observatory for ASD, the actual prevalence in Italy is about 1/77 for children aged between 7 and 9 years, with a 4.4 times higher prevalence in male. The origin of ASD is still largely undefined. It has been hypothesized a possible role for the influence of early life alteration of gut microbiome (GM). We demonstrated an imbalance in Bacteroidetes and Firmicutes phyla with a decrease in Bacteroidetes/Firmicutes ratio in the GM of pediatric patients affected by ASD. Similar data have been observed by others. Data from ASD animal model confirm the presence of GM dysbiosis with significant correlation with behavioral, gastrointestinal and immunologic alterations. Altogether these data support the hypothesis that GM dysbiosis could be involved in the ASD pathogenesis. The ASD children present an increased prevalence of functional gastrointestinal disorders (FGIDs), mainly chronic constipation, functional diarrhea, and irritable bowel syndrome (IBS). A role for GM has been suggested also for these conditions. The presence of these disorders negatively influence the disease severity and the parental quality of life of ASD children. Starting from all these considerations GM is becoming a possible target of intervention for pediatric ASD. Probiotics are one of the most investigated strategy for a beneficial modulation of GM. Probiotics are commonly defined as live microorganisms which when ingested in adequate amounts confer a beneficial effect on the host. The most used probiotics in the pediatric age are Saccharomyces and Lactobacillus strains including Lactobacillus rhamnosus GG (LGG). Data report a beneficial influence elicited by LGG on GM structure and function. This probiotic resulted also effective in treating FGIDs patients. Preliminary evidence suggest the potential efficacy of probiotics for FGIDs treatment in ASD children. Altogether these evidence strongly support the hypothesis that LGG could exert a beneficial action in ASD children. The purpose of this study is to evaluate the therapeutic efficacy of LGG on FGIDs in ASD children.

Interventions

• Other Lactobacillus rhamnosus GG
  Lactobacillus rhamnosus GG
• Other Placebo
  Placebo

Primary outcome measures

• Functional gastrointestinal disorders (FGIDs) severity [Time frame: At 16 weeks of treatment]

Secondary outcome measures (9)

• Kinetics of Lactobacillus rhamnosus GG (LGG) [Time frame: At baseline and at 4 weeks, 8 weeks and 12 weeks of treatment]
• Duration of the LGG impact on FGIDs [Time frame: At baseline and at 4 weeks and 12 weeks from the end of treatment]
• Gut Microbiome (GM) composition [Time frame: At baseline and at 16 weeks of treatment]
• GM function: fecal short chain fatty acids (SCFAs) levels [Time frame: At baseline and at 16 weeks of treatment]
• ASD children behavior [Time frame: At baseline, at 4 weeks, at 8 weeks, at 12 weeks and at 16 weeks of treatment, and at 4 weeks and 12 weeks from the end of treatment]
• Parental quality of life [Time frame: At baseline, at 4 weeks, at 8 weeks, at 12 weeks and at 16 weeks of treatment, and at 4 weeks and 12 weeks from the end of treatment]
• Body weight [Time frame: At baseline, at 4 weeks, at 8 weeks, at 12 weeks and at 16 weeks of treatment, and at 4 weeks and 12 weeks from the end of treatment]
• Height [Time frame: At baseline, at 4 weeks, at 8 weeks, at 12 weeks and at 16 weeks of treatment, and at 4 weeks and 12 weeks from the end of treatment]
• Infectious diseases [Time frame: At 4 weeks, at 8 weeks, at 12 weeks and at 16 weeks of treatment, and at 4 weeks and 12 weeks from the end of treatment]

Eligibility criteria

Inclusion criteria

• children aged 4-12 years
• children of both sex
• children with a sure diagnosis of ASD and presence of FGIDs with a GSI ≥7 from at least 3 months.

Exclusion criteria

• children aged <4 or >12 years
• uncertain ASD and/or FGIDs diagnosis
• FGIDs duration lasting <3 months
• concomitant presence of other chronic conditions (adverse food reactions; genetic and metabolic disorders; malformations of GI, respiratory or urinary tract; neurologic diseases; immunodeficiencies; diabetes; cardiovascular diseases; autoimmune diseases; chronic infections; chronic respiratory, GI or urinary tract diseases; obesity; tumors; malnutrition).
• use of antibiotics and/or pre-/pro-/ synbiotics during the 6 months prior to enrolment
• participation into other clinical trials during the last 12 months.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Italy · 1 center

• Department of Traslational Medical Science - University of Naples Federico II — Naples

Identifiers

NCT: NCT07345585 · 38/2023

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗