search
Back to results

Combined Human Milk Oligosaccharides (HMOs) and Probiotics Intervention for Children With Autism

Primary Purpose

Autism Spectrum Disorder, Neurodevelopmental Disorders, Anxiety

Status
Active
Phase
Not Applicable
Locations
Australia
Study Type
Interventional
Intervention
Experimental
Placebo
Sponsored by
The University of Queensland
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Autism Spectrum Disorder focused on measuring Gut microbiome, Behaviour

Eligibility Criteria

5 Years - 12 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Aged 5.00 years to 12.99 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.

Exclusion Criteria:

  1. Organic GI disorders such as inflammatory bowel disease, coeliac disease, eosinophilic disorders, or current infection of the GI tract.
  2. Bowel surgery or short bowel syndrome
  3. Participants who have a diagnosed cow milk protein allergy.

  4. Participants who suffer from the conditions listed below or who are taking any of the following medications or supplements:

    • antibiotics or antifungals in the last two months
    • probiotic supplements in the last two months
    • immunocompromised or severely ill
    • genetic disorders (e.g. Fragile X Syndrome)
    • chronic health conditions such as diabetes, heart disease or an eating disorder.

Sites / Locations

  • University of Queensland, Child Health Research Centre

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

HMOs + Probiotics

Placebo

Arm Description

Dosing: A total daily dose of 2 x sachets (6g/day) Product Comprised of: 2.5g of a proprietary blend of human milk oligosaccharides combined with 20 billion CFUs of a mixture of Lactobacillus rhamnosus, Lactobacillus plantarum, Bifidobacterium animalis spp. lactis, and Bifidobacterium longum. Mode of administration: oral.

Dosing: A total daily dose of 2 x sachets (6g/day)u (8 weeks of phase 1A). Product: powdered maltodextrin. Mode of administration: oral.

Outcomes

Primary Outcome Measures

Behaviour change
Changes in behavioural symptoms as measured by the Irritability sub-scale of the Aberrant Behavior Checklist - Community (Version 2) (I-ABC). The ABC 58-item parent-rated questionnaire and 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.
Behaviour Change
Changes in behavioural symptoms as measured by the Home Situations Questionnaire - Autism Spectrum Disorder (HSQ-ASD). The HSQ-ASD is a 24-item, parent-rated measure of non compliant behaviour in children with ASD. The scale yields per-item mean scores of 0 to 9, with higher scores indicating greater noncompliance.
Behaviour Change
Changes in parent/guardian targeted behaviours as measured by the Parent Targeted Symptom Visual Analogue Scale (PTSVAS). The PTSVAS tool requests parents/guardians report their top three (3) target behaviours (behaviours of concern) on a Visual Analogue Scale (VAS). The VAS is a horizontal line of 100mm in length, with each end defined as the extreme limits of the behaviour of concern ("best" to "worst"), to be measured from left to right. The parents will score the behaviour by placing a mark on the VAS at baseline and post-intervention. Each mark will be measured on the scale of 0-100mm and the change from baseline to post-intervention noted.

Secondary Outcome Measures

Change in 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.
Change in the Gut Microbiome
This is an explorative outcome to compare and characterise changes in gut (stool) micorbiome between treatment groups. Change or trends (diversity, bacterial species, metabolite potential) in the gut microbiome as analysed using stool shotgun metagenomic sequencing.
Change in Anxiety Levels
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.
Change in Quality of Life
Quality of life (QoL) measured by the Quality of life Autism (QoLA) questionnaire. The QoLA is a 48-item questionnaire divided into 2 subsets (Part A and Part B). The QoLA utilises a 5-point scale (0-4). Possible scores range from 48-240, with higher scores equating to higher perceived QoL.
Change in Stool Consistency
Change in Stool consistency as measured by the Bristol Stool Chart (BSC, paediatric version)
Change in stool short chain fatty acids levels
Change in stool short chain fatty acids levels as measured using gas chromatography with flame ionisation detection (GC-FID)
Change in urinary serotonin concentration
Change in concentrations of the urinary serotonin metabolite, 5-Hydroxyindoleacetic acid as measured using a double solvent front extraction, followed by reversed phase High Performance Liquid Chromatography (HPLC) with electrochemical detection (ECD)
Change in salivary cortisol levels
Change to salivary cortisol levels as measured using the Elecsys® Cortisol II assay

Full Information

First Posted
October 17, 2021
Last Updated
June 26, 2023
Sponsor
The University of Queensland
search

1. Study Identification

Unique Protocol Identification Number
NCT05151601
Brief Title
Combined Human Milk Oligosaccharides (HMOs) and Probiotics Intervention for Children With Autism
Official Title
The Effect of a Combination of Human Milk Oligosaccharides (HMOs) and Probiotics on Behavioural Change in Children With Autism Spectrum Disorder (ASD).
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 17, 2022 (Actual)
Primary Completion Date
April 16, 2023 (Actual)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The University of Queensland

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This research project will investigate if a supplement containing a unique combination of prebiotics and probiotics can influence behaviour in children diagnosed with autism spectrum disorder. The study will use a combination of human milk oligosaccharides (HMOs, prebiotics) and probiotics as an oral powder.This clinical trial will have two consecutive phases. Phase 1A is an 8-week randomised, double-blinded, placebo-controlled trial. Participants will be recruited and randomised (1:1) to receive either the investigational product (treatment group, n=30) or the placebo (control group, n=30). Phase 1B is an 8-week open-label study. All participants that complete Phase 1A will move into Phase 1B (n=60). This allows all participants to receive the investigational product and will provide additional information on increased duration of treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autism Spectrum Disorder, Neurodevelopmental Disorders, Anxiety
Keywords
Gut microbiome, Behaviour

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Participants will be recruited into a two-phase project. Phase 1A: an 8-week double-blinded, placebo-controlled, randomised trial. Participants child will be randomised to one of groups 1) treatment (HMOs/Probiotic group) or 2) control group (placebo product). Phase 1B: is an 8-week open-label trial. All children who successfully complete phase 1A will be recruited into phase 1B. All participants in phase 1B will receive the treatment product (HMOs/probiotics). Follow up will occur at week 8 and week 17.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
HMOs + Probiotics
Arm Type
Experimental
Arm Description
Dosing: A total daily dose of 2 x sachets (6g/day) Product Comprised of: 2.5g of a proprietary blend of human milk oligosaccharides combined with 20 billion CFUs of a mixture of Lactobacillus rhamnosus, Lactobacillus plantarum, Bifidobacterium animalis spp. lactis, and Bifidobacterium longum. Mode of administration: oral.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Dosing: A total daily dose of 2 x sachets (6g/day)u (8 weeks of phase 1A). Product: powdered maltodextrin. Mode of administration: oral.
Intervention Type
Dietary Supplement
Intervention Name(s)
Experimental
Intervention Description
2 x sachets per day
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
2 x sachets per day
Primary Outcome Measure Information:
Title
Behaviour change
Description
Changes in behavioural symptoms as measured by the Irritability sub-scale of the Aberrant Behavior Checklist - Community (Version 2) (I-ABC). The ABC 58-item parent-rated questionnaire and 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.
Time Frame
Baseline, Phase IA midpoint (week 4) and post-Phase 1A(week 8/9), post-Phase 1B (week 17/18)
Title
Behaviour Change
Description
Changes in behavioural symptoms as measured by the Home Situations Questionnaire - Autism Spectrum Disorder (HSQ-ASD). The HSQ-ASD is a 24-item, parent-rated measure of non compliant behaviour in children with ASD. The scale yields per-item mean scores of 0 to 9, with higher scores indicating greater noncompliance.
Time Frame
Baseline, Phase 1A midpoint (week 4) and post-Phase 1A (week 8/9)
Title
Behaviour Change
Description
Changes in parent/guardian targeted behaviours as measured by the Parent Targeted Symptom Visual Analogue Scale (PTSVAS). The PTSVAS tool requests parents/guardians report their top three (3) target behaviours (behaviours of concern) on a Visual Analogue Scale (VAS). The VAS is a horizontal line of 100mm in length, with each end defined as the extreme limits of the behaviour of concern ("best" to "worst"), to be measured from left to right. The parents will score the behaviour by placing a mark on the VAS at baseline and post-intervention. Each mark will be measured on the scale of 0-100mm and the change from baseline to post-intervention noted.
Time Frame
Baseline and post-Phase 1A (week 8/9)
Secondary Outcome Measure Information:
Title
Change in GI Symptom Severity
Description
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.
Time Frame
Baseline and post-Phase 1A (week 8/9)
Title
Change in the Gut Microbiome
Description
This is an explorative outcome to compare and characterise changes in gut (stool) micorbiome between treatment groups. Change or trends (diversity, bacterial species, metabolite potential) in the gut microbiome as analysed using stool shotgun metagenomic sequencing.
Time Frame
Baseline and post-Phase 1A (week 8/9)
Title
Change in Anxiety Levels
Description
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.
Time Frame
Baseline and post-Phase 1A (week 8/9)
Title
Change in Quality of Life
Description
Quality of life (QoL) measured by the Quality of life Autism (QoLA) questionnaire. The QoLA is a 48-item questionnaire divided into 2 subsets (Part A and Part B). The QoLA utilises a 5-point scale (0-4). Possible scores range from 48-240, with higher scores equating to higher perceived QoL.
Time Frame
Baseline and post-Phase 1A (week 8/9)
Title
Change in Stool Consistency
Description
Change in Stool consistency as measured by the Bristol Stool Chart (BSC, paediatric version)
Time Frame
Baseline, Phase A1 midpoint (week 4), and post-Phase 1A (week 8/9), post-Phase 1B (week 17/18) .
Title
Change in stool short chain fatty acids levels
Description
Change in stool short chain fatty acids levels as measured using gas chromatography with flame ionisation detection (GC-FID)
Time Frame
Baseline and post-Phase 1A (weeks 8/9)
Title
Change in urinary serotonin concentration
Description
Change in concentrations of the urinary serotonin metabolite, 5-Hydroxyindoleacetic acid as measured using a double solvent front extraction, followed by reversed phase High Performance Liquid Chromatography (HPLC) with electrochemical detection (ECD)
Time Frame
Baseline and post-Phase 1A (weeks 8/9)
Title
Change in salivary cortisol levels
Description
Change to salivary cortisol levels as measured using the Elecsys® Cortisol II assay
Time Frame
Baseline and post-Phase 1A (weeks 8/9)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Aged 5.00 years to 12.99 years. 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. Exclusion Criteria: Organic GI disorders such as inflammatory bowel disease, coeliac disease, eosinophilic disorders, or current infection of the GI tract. Bowel surgery or short bowel syndrome Participants who have a diagnosed cow milk protein allergy. Participants who suffer from the conditions listed below or who are taking any of the following medications or supplements: antibiotics or antifungals in the last two months probiotic supplements in the last two months immunocompromised or severely ill genetic disorders (e.g. Fragile X Syndrome) chronic health conditions such as diabetes, heart disease or an eating disorder.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter SW Davies, PhD
Organizational Affiliation
The University of Queensland
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Queensland, Child Health Research Centre
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
4001
Country
Australia

12. IPD Sharing Statement

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

Learn more about this trial

Combined Human Milk Oligosaccharides (HMOs) and Probiotics Intervention for Children With Autism

We'll reach out to this number within 24 hrs