Combined Gut-brain Therapy for Children With Autism

Overview

CLINICAL ISSUE: Children with Autism Spectrum Disorder (ASD) are four times more likely to suffer with functional gastrointestinal disorders (FGIDs) than their neurotypical peers. The presence of FGIDs are linked to increased undesirable behaviour and ASD severity. Current behavioural approaches for ASD therapy do not alleviate the high comorbidity of FGIDs within this population. BACKGROUND: Dysfunction of the microbiome-gut-brain (MGB) axis has been implicated in pathogenesis of both ASD and FGIDs. Probiotics and prebiotics can modulate the gut microbiome and research has shown efficacy at improving gastrointestinal (GI) symptoms in children with ASD and neurotypical (NT) children with FGIDs. Gut-directed hypnotherapy (GDH) has shown utility in treating FGIDs in NT children and adults but has not yet been trialed in children with ASD. Targeting therapies to address the dysfunction of the bidirectional MGB axis will likely be more effective than either brain/behavioural or gut-based therapy alone. HYPOTHESIS: A synbiotic (prebiotic + probiotic mixture) with combined GDH will be more effective than either a synbiotic or GDH alone at reducing GI symptoms in children with ASD aged 5.00 to 10.99 years over a 12-week period.

Full Title of Study: “The Utility of a Synbiotic With Adjunct Gut-directed Hypnotherapy on the Severity of Gastrointestinal Symptoms in Children With Autism”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 15, 2021

Interventions

  • Combination Product: Synbiotic
    • Prebiotic + Probiotic
  • Behavioral: Gut-directed Hypnotherapy
    • Psychotherapy sessions

Arms, Groups and Cohorts

  • Active Comparator: Synbiotic
    • Dosing: one sachet/dose per day for 12 weeks. The combination includes: Lactobacillus rhamnosus (1×10^10 CFU/dose), Lactobacillus plantarum (4 x 10^9 CFU/dose), Bifidobacterium animalis subsp. lactis (5 x 10^9 CFU/dose), Bifidobacterium longum (1 x 10^9 CFU/dose) + 4g/dose of partially hydrolysed guar gum (PHGG). Mode of administration: oral.
  • Active Comparator: Gut-directed Hypnotherapy
    • Schedule: Six, 1-hour sessions over 12 weeks + daily at-home audio (optional 5-20 min). Mode: face-to-face (virtual and/or in person) sessions. Overview: based on the Manchester model of GDH adapted for use in children with ASD. The GDH core therapy focus areas will be relaxation, control of gut function and ego-strengthening. Optional at-home audio will be a summary of content from the session for the previous in clinic session.
  • Experimental: Combined
    • Includes both the daily oral synbiotic + six, 1-hour GDH sessions over 12 week intervention.

Clinical Trial Outcome Measures

Primary Measures

  • GI symptom severity
    • Time Frame: Baseline, 12 weeks, 24 weeks
    • Change in GI symptom severity as measured by the 6-item gastrointestinal severity index (6-GSI). The 6-GSI assesses each GI symptom using a Likert scale of 0-2 (0 = nil/mild/infrequent; 1 = moderate/occasional; 2 = severe/frequent). Score range 0-12. Mild GI issues are defined as a score of under three and moderate or severe GI issues defined as a score of three or above.

Secondary Measures

  • ASD severity/behaviour
    • Time Frame: Baseline, 12 weeks
    • Change in ASD severity scores as measured by the Aberrant Behaviour Checklist (ABC) questionnaire. The ABC consists of five subscales, including: 1) irritability (15 items); 2) lethargy/social withdrawal(16 items); 3) Stereotypic Behaviour (7 items); 4) hyperactivity/noncompliance (16 items); and 5) Inappropriate Speech (4 items). Each item is scored as 0=never a problem, 1=slight problem, 2=moderately serious problem, or 3= severe problem. The score range is 0-174, with a higher score indicating greater severity or difficulties.
  • Anxiety
    • Time Frame: Baseline, 12 weeks
    • Change in anxiety levels as measured by the Parent Rated Anxiety Scale – Autism Spectrum Disorder (PRAS-ASD) questionnaire. This is a 25-item tool using a Likert scale of 0-3 (0=none; 1=mild; 2=moderate; 3=severe). Score range 0-75, with higher scores indicating greater levels of anxiety.
  • Gut microbiome
    • Time Frame: Baseline, 12 weeks
    • This is an explorative outcome to compare and characterise changes in gut (stool) microbiome composition and functional profiles using shotgun metagenomic sequencing.

Participating in This Clinical Trial

Inclusion Criteria

1. Aged 5.00 years to 10.99 years 2. A confirmed diagnosis of ASD or Pervasive Developmental Disorders (PDD) including autistic disorder, Asperger's disorder (AS); PDD not otherwise specified (PDD-NOS); and atypical autism. 3. A diagnosis of a functional gastrointestinal disorder (FGID) by a gastroenterologist or a score of three and above on the six-item gastrointestinal severity index (6-GSI). Accepted FGIDs include diarrhoea, constipation, bloating, abdominal pain or irritable bowel syndrome (IBS). Exclusion Criteria:

1. Non-verbal children and/or those with severe cognitive impairment 2. Confirmed diagnosis of inflammatory bowel disease, coeliac disease, or current infection of the GI tract. 3) Any other medication, supplement or conditions which can impact the gut microbiome, including:

  • antibiotics or antifungals in the last month – probiotic or prebiotic supplements in the last two weeks – immunocompromised or severely ill – bipolar, schizophrenia, personality disorders – diabetes mellitus or an eating disorder
  • Gender Eligibility: All

    Minimum Age: 5 Years

    Maximum Age: 10 Years

    Are Healthy Volunteers Accepted: No

    Investigator Details

    • Lead Sponsor
      • The University of Queensland
    • Provider of Information About this Clinical Study
      • Sponsor
    • Overall Official(s)
      • Leanne K Mitchell, B.HlthSc (Hons), Principal Investigator, The University of Queensland
    • Overall Contact(s)
      • Leanne K Mitchell, B.HlthSc(Hons), +61414689850, leanne.mitchell@uq.edu.au

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