Combined Gut-brain Therapy for Children With Autism

• ClinicalTrials.gov Identifier: NCT04639141
• Recruitment Status: Active, not recruiting
• First Posted: November 20, 2020
• Last Update Posted: January 11, 2022
• Sponsor: The University of Queensland
• Information provided by (Responsible Party): The University of Queensland

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Autism Spectrum Disorder; Functional Gastrointestinal Disorders; Neurodevelopmental Disorders; Anxiety	Combination Product: Synbiotic; Behavioral: Gut-directed Hypnotherapy	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Participants will be recruited and randomised (1:1) to one of two 12-week treatment intervention groups: 1) synbiotic or 2) synbiotic + gut-directed hypnotherapy. Follow-up will occur at week 24.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Utility of a Synbiotic With Adjunct Gut-directed Hypnotherapy on the Severity of Gastrointestinal Symptoms in Children With Autism
• Actual Study Start Date: December 1, 2020
• Estimated Primary Completion Date: April 1, 2022
• Estimated Study Completion Date: June 30, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 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 Outcome Measures :

1. 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.
2. 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.
3. 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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Australia, Queensland

University of Queensland, Child Health Research Centre, Faculty of Medicine

Brisbane, Queensland, Australia, 4101

Sponsors and Collaborators

The University of Queensland

Investigators

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

More Information

• Responsible Party: The University of Queensland
• ClinicalTrials.gov Identifier: NCT04639141
• Other Study ID Numbers: ASD-MGB-RCT2020
• First Posted: November 20, 2020
• Last Update Posted: January 11, 2022
• Last Verified: January 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: IPD is the intellectual property of the funding industry partner.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Gastrointestinal Diseases; Digestive System Diseases; Disease; Autistic Disorder; Autism Spectrum Disorder; Neurodevelopmental Disorders; Pathologic Processes; Child Development Disorders, Pervasive; Mental Disorders