Combined Gut-brain Therapy for Children With Autism

The Utility of a Synbiotic With Adjunct Gut-directed Hypnotherapy on the Severity of Gastrointestinal Symptoms in Children With Autism

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 a synbiotic alone at reducing GI symptoms in children with ASD aged 5.00 to 10.99 years over a 12-week period.

Study Overview

• Status: Completed
• Conditions: Anxiety; Neurodevelopmental Disorders; Functional Gastrointestinal Disorders; Autism Spectrum Disorder
• Intervention / Treatment: Combination product: Synbiotic; Behavioral: Gut-directed Hypnotherapy

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Brisbane, Queensland, Australia, 4101
      • University of Queensland, Child Health Research Centre, Faculty of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 10 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Synbiotic; Dosing: one sachet/dose per day for 12 weeks. The combination includes: Lactobacillus rhamnosus (1x10^10 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.	Combination product: Synbiotic; Prebiotic + Probiotic
Experimental: Synbiotic + gut-directed hypnotherapy; Includes the daily oral synbiotic (as pervious described) + a home-based therapy program. Home-based therapy program: based on the Manchester model of gut-directed hypnotherapy (GDH) adapted for use in children with ASD. The GDH core therapy focus areas will be relaxation, control of gut function and ego-strengthening. Schedule: daily use of a home-based audio recordings. The program will consist of six (6) therapy sessions/recordings over 12 weeks. Each recording (sessions 1 through 6) is to be used daily for a fortnight. Each session is approximately 15-20 minutes in duration.	Combination product: Synbiotic; Prebiotic + Probiotic; Behavioral: Gut-directed Hypnotherapy; Psychotherapy sessions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GI symptom severity	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.	Baseline, 12 weeks, 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ASD severity/behaviour	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.	Baseline, 12 weeks
Anxiety	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.	Baseline, 12 weeks
Gut microbiome	This is an explorative outcome to compare and characterise changes in gut (stool) microbiome composition and functional profiles using shotgun metagenomic sequencing.	Baseline, 12 weeks

Collaborators and Investigators

• Sponsor: The University of Queensland
• Investigators: Principal Investigator: Leanne K Mitchell, B.HlthSc (Hons), The University of Queensland

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2021
• Primary Completion (Actual): April 1, 2022
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: November 16, 2020
• First Submitted That Met QC Criteria: November 16, 2020
• First Posted (Actual): November 20, 2020

Study Record Updates

• Last Update Posted (Actual): September 6, 2023
• Last Update Submitted That Met QC Criteria: September 4, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Child Development Disorders, Pervasive; Gastrointestinal Diseases; Digestive System Diseases; Autistic Disorder; Autism Spectrum Disorder; Neurodevelopmental Disorders
• Other Study ID Numbers: ASD-MGB-RCT2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD is the intellectual property of the funding industry partner.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No