Combined Gut-brain Therapy for Children With Autism

Not Applicable

Completed

• Conditions: Functional Gastrointestinal Disorders; Anxiety; Autism Spectrum Disorder; Neurodevelopmental Disorders
• Interventions: Combination Product: Synbiotic; Behavioral: Gut-directed Hypnotherapy

• Registration Number: NCT04639141
• Lead Sponsor: The University of Queensland

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-11-16
• Study First Submitted QC: 2020-11-16
• Study First Posted: 2020-11-20
• Study Start: 2021-12-01
• Primary Completion: 2022-04-01
• Study Completion: 2022-06-30
• Status Verified: 2023-08
• Last Update Submitted: 2023-09-04
• Last Update Posted: 2023-09-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Synbiotic + gut-directed hypnotherapy	Synbiotic	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.
Synbiotic	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.
Synbiotic + gut-directed hypnotherapy	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.

Primary Outcome Measures

Name	Time	Method
GI symptom severity	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 Outcome Measures

Name	Time	Method
Anxiety	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	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.
ASD severity/behaviour	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.

Trial Locations

Locations (1)

University of Queensland, Child Health Research Centre, Faculty of Medicine; 🇦🇺 Brisbane, Queensland, Australia