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AzTrials

Autism Spectrum DisorderNCT02708901

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

A study testing Vivomixx® in people with Autism Spectrum Disorder, run by IRCCS Fondazione Stella Maris at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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… Read more about this study

Who is it for?
Ages 18 to 72 months
Conditions the study is for
Autism Spectrum Disorder
What is being tested?
Vivomixx®
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
85 participants
Where
1 siteItaly
Study dates
Nov 2015to Sep 2018
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 72 months
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

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

Who cannot join

  • 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)

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • IRCCS Stella Maris Foundation

    Calambrone, Pisa, 56128

Other trials in Italy

About this study

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.

Read the 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.

Being tested
Vivomixx®, Placebo
Keywords
Autism Spectrum Disorder, Probiotic Vivomixx®, Gastrointestinal Symptoms, Gut-Brain Axis, Endophenotypes
Medical subject headings
Autism Spectrum Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Vivomixx®Dietary supplement

    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

  • PlaceboDietary supplement

    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

Study groups in NCT02708901
Study groupRoleWhat they receive
GI Vivomixx®Active comparator25 children with GI symptoms
Receives: Dietary Supplement: Vivomixx®
GI PlaceboPlacebo comparator25 children with GI symptoms
Receives: Dietary Supplement: Placebo
NGI Vivomixx®Active comparator25 children without GI symptoms
Receives: Dietary Supplement: Vivomixx®
NGI placeboPlacebo comparator25 children without GI symptoms
Receives: Dietary Supplement: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Changes in severity level of ASD symptomatology

    Delta of scores at Autism Diagnostic Observation Schedule-2

    Measured: 6 months

Secondary outcomes (19)

  1. Changes in GI symptomatology

    Delta of scores at GI Severity Index

    Measured: 3 months and 6 months

  2. Changes in Electroencephalogram (EEG) power

    Registration with a 128-channels digital EEG: power will be assessed within each frequency band

    Measured: 6 months

  3. Changes in EEG coherence

    Registration with a 128-channels digital EEG: coherence will be assessed within each frequency band

    Measured: 6 months

  4. Changes in EEG asymmetry

    Registration with a 128-channels digital EEG: asymmetry will be assessed within each frequency band

    Measured: 6 months

  5. Changes in levels of serum Lipopolysaccharide

    Delta of values of serum Lipopolysaccharide

    Measured: 6 months

  6. Changes in levels of serum Leptin

    Delta of values of serum Leptin

    Measured: 6 months

  7. Changes in levels of serum Resistin

    Delta of values of serum Resistin

    Measured: 6 months

  8. Changes in levels of serum Tumor Necrosis Factor - alfa

    Delta of values of serum Tumor Necrosis Factor - alfa

    Measured: 6 months

  9. Changes in levels of serum Interleukin-6 (IL-6)

    Delta of values of serum Interleukin-6 (IL-6)

    Measured: 6 months

  10. Changes in levels of serum Plasminogen Activator Inhibitor-1 (PAI-1)

    Delta of values of serum Plasminogen Activator Inhibitor-1 (PAI-1)

    Measured: 6 months

  11. Changes in levels of fecal calprotectin

    Delta of values of fecal calprotectin

    Measured: 3 months and 6 months

  12. Changes in global ASD symptomatology assessed by Childhood Autism Rating Scale

    Delta of scores at Childhood Autism Rating Scale

    Measured: 6 months

  13. Changes in ASD symptomatology: repetitive behaviors

    Delta of scores at Repetitive Behavior Scale

    Measured: 3 months and 6 months

  14. Changes in ASD symptomatology: sensory profiles

    Delta of scores at Sensory Profile

    Measured: 3 months and 6 months

  15. Changes in global ASD symptomatology assessed by Social Communication Questionnaire

    Delta of scores at Social Communication Questionnaire

    Measured: 3 months and 6 months

  16. Changes in Developmental Quotient

    Delta of score at Griffiths Mental Developmental Scale

    Measured: 6 months

  17. Changes in Adaptive Functioning

    Delta of scores at Vineland Adaptive Behavior Scale-II

    Measured: 6 months

  18. Changes in Behavioral Profiles

    Delta of scores at Child Behavior Checklist 1.5-5

    Measured: 3 months and 6 months

  19. Changes in Parental Stress

    Delta of scores at Parenting Stress Index

    Measured: 3 months and 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Mar 2016 (estimated)
  2. Study startNov 2015
  3. Primary completionAug 2018
  4. Study completionSep 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomized double blind study of dietary supplement compared to placebo
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
85 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02708901
Sponsor's protocol ID
GR-2011-02348280
Status last verified
Aug 2017
First submitted
4 Mar 2016
Last updated
18 Feb 2019
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 26748423

  • 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.

    PubMed 27260271

  • 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. doi: 10.1186/s13052-016-0308-x.

    PubMed 27852289

  • 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.

    PubMed 28861653

  • Santocchi E, Guiducci L, Prosperi M, Calderoni S, Gaggini M, Apicella F, Tancredi R, Billeci L, Mastromarino P, Grossi E, Gastaldelli A, Morales MA, Muratori F. Effects of Probiotic Supplementation on Gastrointestinal, Sensory and Core Symptoms in Autism Spectrum Disorders: A Randomized Controlled Trial. Front Psychiatry. 2020 Sep 25;11:550593. doi: 10.3389/fpsyt.2020.550593. eCollection 2020.

    PubMed 33101079

Questions about this trial

What is this clinical trial studying?

A study testing Vivomixx® in people with Autism Spectrum Disorder, run by IRCCS Fondazione Stella Maris at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes in severity level of ASD symptomatology (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02708901, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2019.

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