Gut to Brain Interaction in Autism. Role of Probiotics on Clinical, Biochemical and Neurophysiological Parameters

Sponsor

IRCCS Fondazione Stella Maris (Other)

Overall Status

Completed

CT.gov ID

NCT02708901

Collaborator

Ministry of Health, Italy (Other), Istituto di Fisiologia Clinica CNR (Other)

Enrollment

Location

Arms

Actual Duration (Months)

2.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the effects of a 6-months supplementation with probiotic Vivomixx® on inflammatory and gastrointestinal (GI) biomarkers, gastrointestinal disturbances, behavioral and developmental profiles, and neurophysiological features in preschoolers with Autism Spectrum Disorders (ASD) with or without GI symptoms.

Condition or Disease	Intervention/Treatment	Phase
Autism Spectrum Disorder	Dietary Supplement: Vivomixx® Dietary Supplement: Placebo	N/A

Detailed Description

Autism Spectrum Disorders (ASD) are most likely multifactorial diseases in which the combination of genetic and environmental factors might have a role in the expression of the phenotype. A high incidence of gastrointestinal (GI) symptoms is reported in ASD. GI disturbances and altered gut microflora could make a child with a genetic predisposition for ASD more prone to express the ASD phenotype or increase the severity of his behavioral symptoms. The exploitation of strategies which can reduce the gut production and absorption of toxins or restore normal gut microbiota, such as probiotics may represent a non-pharmacological option in the treatment of GI disturbances in ASD. The aim of this study is to determine effects of probiotics supplementation with Vivomixx® in ASD children on specific GI symptoms, ASD core deficits, cognitive and language development, on inflammatory and gastrointestinal (GI) biomarkers and on Quantitative Electroencephalographic measures (QEEG). Vivomixx® is a probiotic mixture of 8 probiotic strains (Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasei, Lactobacillus bulgaricus and Streptococcus thermophilus). An additional aim of the study is to determine the environmental exposure to phthalates (chemical pollutant) in ASD children, and the possible effects of probiotic supplementation on their urinary concentrations. A group of 100 unselected preschoolers with ASD will be classified as belonging to the Gastro Intestinal (GI) group or to the Not Gastro Intestinal (NGI) group on the basis of the presence of significant GI symptoms at GI severity Index. Subjects belonging to the two groups (GI and NGI) will be blind randomized 1:1 to regular diet with probiotic Vivomixx® or with placebo for 6 months. All the participants will be assessed at the baseline, after three months and after six months from the baseline in order to evaluate the possible changes in GI symptoms, in ASD symptomatology, in other affective and behavioral comorbid symptoms, in plasmatic, urinary and fecal biomarkers related to abnormal intestinal function and in the electrophysiological patterns. The effects of treatments with probiotics on children with ASD need to be confirmed by rigorous controlled trials. Aiming to examine the impact of this treatment not only on clinical but also on neurophysiological patterns this trial sets out to provide new insights into the gut-brain connection in autism. Moreover, this study's results could add new data on the relationship between the presence of phthalates, clinical features and neurophysiological patterns in ASD.

Study Design

Study Type:

Interventional

Actual Enrollment :

85 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized double blind study of dietary supplement compared to placeboRandomized double blind study of dietary supplement compared to placebo

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Gut to Brain Interaction in Autism. Role of Probiotics on Clinical, Biochemical and Neurophysiological Parameters

Actual Study Start Date :

Nov 1, 2015

Actual Primary Completion Date :

Aug 1, 2018

Actual Study Completion Date :

Sep 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: GI Vivomixx® 25 children with GI symptoms	Dietary Supplement: Vivomixx® Two packets (900 billions bacteria) per os (P.O.) daily x 1 month and one packet (450 billions bacteria) P.O. daily x 5 months
Placebo Comparator: GI Placebo 25 children with GI symptoms	Dietary Supplement: Placebo Two packets (4,4 grams of maltose and silicon dioxide x 2) P.O. daily x 1 month and one packet (4,4 grams of maltose and silicon dioxide) P.O. daily x 5 months
Active Comparator: NGI Vivomixx® 25 children without GI symptoms	Dietary Supplement: Vivomixx® Two packets (900 billions bacteria) per os (P.O.) daily x 1 month and one packet (450 billions bacteria) P.O. daily x 5 months
Placebo Comparator: NGI placebo 25 children without GI symptoms	Dietary Supplement: Placebo Two packets (4,4 grams of maltose and silicon dioxide x 2) P.O. daily x 1 month and one packet (4,4 grams of maltose and silicon dioxide) P.O. daily x 5 months

Outcome Measures

Primary Outcome Measures

Changes in severity level of ASD symptomatology [6 months]
Delta of scores at Autism Diagnostic Observation Schedule-2

Secondary Outcome Measures

Changes in GI symptomatology [3 months and 6 months]
Delta of scores at GI Severity Index
Changes in Electroencephalogram (EEG) power [6 months]
Registration with a 128-channels digital EEG: power will be assessed within each frequency band
Changes in EEG coherence [6 months]
Registration with a 128-channels digital EEG: coherence will be assessed within each frequency band
Changes in EEG asymmetry [6 months]
Registration with a 128-channels digital EEG: asymmetry will be assessed within each frequency band
Changes in levels of serum Lipopolysaccharide [6 months]
Delta of values of serum Lipopolysaccharide
Changes in levels of serum Leptin [6 months]
Delta of values of serum Leptin
Changes in levels of serum Resistin [6 months]
Delta of values of serum Resistin
Changes in levels of serum Tumor Necrosis Factor - alfa [6 months]
Delta of values of serum Tumor Necrosis Factor - alfa
Changes in levels of serum Interleukin-6 (IL-6) [6 months]
Delta of values of serum Interleukin-6 (IL-6)
Changes in levels of serum Plasminogen Activator Inhibitor-1 (PAI-1) [6 months]
Delta of values of serum Plasminogen Activator Inhibitor-1 (PAI-1)
Changes in levels of fecal calprotectin [3 months and 6 months]
Delta of values of fecal calprotectin
Changes in global ASD symptomatology assessed by Childhood Autism Rating Scale [6 months]
Delta of scores at Childhood Autism Rating Scale
Changes in ASD symptomatology: repetitive behaviors [3 months and 6 months]
Delta of scores at Repetitive Behavior Scale
Changes in ASD symptomatology: sensory profiles [3 months and 6 months]
Delta of scores at Sensory Profile
Changes in global ASD symptomatology assessed by Social Communication Questionnaire [3 months and 6 months]
Delta of scores at Social Communication Questionnaire
Changes in Developmental Quotient [6 months]
Delta of score at Griffiths Mental Developmental Scale
Changes in Adaptive Functioning [6 months]
Delta of scores at Vineland Adaptive Behavior Scale-II
Changes in Behavioral Profiles [3 months and 6 months]
Delta of scores at Child Behavior Checklist 1.5-5
Changes in Parental Stress [3 months and 6 months]
Delta of scores at Parenting Stress Index

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Months to 72 Months

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

age-range: 18-72 months
ASD diagnosis according to Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) criteria

Exclusion Criteria:

brain anomalies detected by Magnetic Resonance Imaging (MRI)
neurological syndromes or focal neurological signs
anamnesis of birth asphyxia, severe premature birth (≤ 28 gestational weeks) or perinatal injuries
epilepsy
significant sensory impairment
diagnosis of organic GI Disorder (i.e. gastroesophageal reflux, food allergies, Inflammatory Bowel Disease)
diagnosis of Coeliac Disease
special diet (i.e. gluten-free diet, casein-free diet, high-protein diet, ketogenic diet)