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

Autism Spectrum Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02708901
• Other study ID #: GR-2011-02348280
• Status: Completed
• Phase: N/A
• Start date: November 2015
• Est. completion date: September 2018

Study information

• Verified date: August 2017
• Source: IRCCS Fondazione Stella Maris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 85
• Est. completion date: September 2018
• Est. primary completion date: August 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Months to 72 Months

Eligibility

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)

Related Conditions & MeSH terms

• Autism Spectrum Disorder
• Autistic Disorder
• Child Development Disorders, Pervasive

Intervention

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
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

Locations

Country	Name	City	State
Italy	IRCCS Stella Maris Foundation	Calambrone	Pisa

Sponsors (3)

Lead Sponsor	Collaborator
IRCCS Fondazione Stella Maris	Istituto di Fisiologia Clinica CNR, Ministry of Health, Italy

Country where clinical trial is conducted

Italy, 

References & Publications (4)

Calderoni S, Santocchi E, Del Bianco T, Brunori E, Caponi L, Paolicchi A, Fulceri F, Prosperi M, Narzisi A, Cosenza A, Tancredi R, Muratori F. Serological screening for Celiac Disease in 382 pre-schoolers with Autism Spectrum Disorder. Ital J Pediatr. 2016 Nov 16;42(1):98. — View Citation

Fulceri F, Morelli M, Santocchi E, Cena H, Del Bianco T, Narzisi A, Calderoni S, Muratori F. Gastrointestinal symptoms and behavioral problems in preschoolers with Autism Spectrum Disorder. Dig Liver Dis. 2016 Mar;48(3):248-54. doi: 10.1016/j.dld.2015.11.026. Epub 2015 Dec 11. — View Citation

Prosperi M, Santocchi E, Balboni G, Narzisi A, Bozza M, Fulceri F, Apicella F, Igliozzi R, Cosenza A, Tancredi R, Calderoni S, Muratori F. Behavioral Phenotype of ASD Preschoolers with Gastrointestinal Symptoms or Food Selectivity. J Autism Dev Disord. 2017 Nov;47(11):3574-3588. doi: 10.1007/s10803-017-3271-5. — View Citation

Santocchi E, Guiducci L, Fulceri F, Billeci L, Buzzigoli E, Apicella F, Calderoni S, Grossi E, Morales MA, Muratori F. Gut to brain interaction in Autism Spectrum Disorders: a randomized controlled trial on the role of probiotics on clinical, biochemical and neurophysiological parameters. BMC Psychiatry. 2016 Jun 4;16:183. doi: 10.1186/s12888-016-0887-5. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in severity level of ASD symptomatology	Delta of scores at Autism Diagnostic Observation Schedule-2	6 months
Secondary	Changes in GI symptomatology	Delta of scores at GI Severity Index	3 months and 6 months
Secondary	Changes in Electroencephalogram (EEG) power	Registration with a 128-channels digital EEG: power will be assessed within each frequency band	6 months
Secondary	Changes in EEG coherence	Registration with a 128-channels digital EEG: coherence will be assessed within each frequency band	6 months
Secondary	Changes in EEG asymmetry	Registration with a 128-channels digital EEG: asymmetry will be assessed within each frequency band	6 months
Secondary	Changes in levels of serum Lipopolysaccharide	Delta of values of serum Lipopolysaccharide	6 months
Secondary	Changes in levels of serum Leptin	Delta of values of serum Leptin	6 months
Secondary	Changes in levels of serum Resistin	Delta of values of serum Resistin	6 months
Secondary	Changes in levels of serum Tumor Necrosis Factor - alfa	Delta of values of serum Tumor Necrosis Factor - alfa	6 months
Secondary	Changes in levels of serum Interleukin-6 (IL-6)	Delta of values of serum Interleukin-6 (IL-6)	6 months
Secondary	Changes in levels of serum Plasminogen Activator Inhibitor-1 (PAI-1)	Delta of values of serum Plasminogen Activator Inhibitor-1 (PAI-1)	6 months
Secondary	Changes in levels of fecal calprotectin	Delta of values of fecal calprotectin	3 months and 6 months
Secondary	Changes in global ASD symptomatology assessed by Childhood Autism Rating Scale	Delta of scores at Childhood Autism Rating Scale	6 months
Secondary	Changes in ASD symptomatology: repetitive behaviors	Delta of scores at Repetitive Behavior Scale	3 months and 6 months
Secondary	Changes in ASD symptomatology: sensory profiles	Delta of scores at Sensory Profile	3 months and 6 months
Secondary	Changes in global ASD symptomatology assessed by Social Communication Questionnaire	Delta of scores at Social Communication Questionnaire	3 months and 6 months
Secondary	Changes in Developmental Quotient	Delta of score at Griffiths Mental Developmental Scale	6 months
Secondary	Changes in Adaptive Functioning	Delta of scores at Vineland Adaptive Behavior Scale-II	6 months
Secondary	Changes in Behavioral Profiles	Delta of scores at Child Behavior Checklist 1.5-5	3 months and 6 months
Secondary	Changes in Parental Stress	Delta of scores at Parenting Stress Index	3 months and 6 months