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

• ClinicalTrials.gov Identifier: NCT05151601
• Recruitment Status: Active, not recruiting
• First Posted: December 9, 2021
• Last Update Posted: February 15, 2023
• Sponsor: The University of Queensland
• Information provided by (Responsible Party): The University of Queensland

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.

Condition or disease	Intervention/treatment	Phase
Autism Spectrum Disorder; Neurodevelopmental Disorders; Anxiety	Dietary Supplement: Experimental; Other: Placebo	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment

Intervention 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)
• Primary Purpose: Treatment
• Official Title: The Effect of a Combination of Human Milk Oligosaccharides (HMOs) and Probiotics on Behavioural Change in Children With Autism Spectrum Disorder (ASD).
• Actual Study Start Date: May 17, 2022
• Estimated Primary Completion Date: April 30, 2023
• Estimated Study Completion Date: December 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: HMOs + Probiotics; 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.	Dietary Supplement: Experimental; 2 x sachets per day
Placebo Comparator: Placebo; Dosing: A total daily dose of 2 x sachets (6g/day)u (8 weeks of phase 1A). Product: powdered maltodextrin. Mode of administration: oral.	Other: Placebo; 2 x sachets per day

Outcome Measures

Primary Outcome Measures :

1. Behaviour change [ Time Frame: Baseline, Phase IA midpoint (week 4) and post-Phase 1A(week 8/9), post-Phase 1B (week 17/18) ]
   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.
2. Behaviour Change [ Time Frame: Baseline, Phase 1A midpoint (week 4) and post-Phase 1A (week 8/9) ]
   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.
3. Behaviour Change [ Time Frame: Baseline and post-Phase 1A (week 8/9) ]
   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 :

1. Change in GI Symptom Severity [ Time Frame: Baseline and post-Phase 1A (week 8/9) ]
   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.
2. Change in the Gut Microbiome [ Time Frame: Baseline and post-Phase 1A (week 8/9) ]
   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.
3. Change in Anxiety Levels [ Time Frame: Baseline and post-Phase 1A (week 8/9) ]
   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.
4. Change in Quality of Life [ Time Frame: Baseline and post-Phase 1A (week 8/9) ]
   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.
5. Change in Stool Consistency [ Time Frame: Baseline, Phase A1 midpoint (week 4), and post-Phase 1A (week 8/9), post-Phase 1B (week 17/18) . ]
   Change in Stool consistency as measured by the Bristol Stool Chart (BSC, paediatric version)
6. Change in stool short chain fatty acids levels [ Time Frame: Baseline and post-Phase 1A (weeks 8/9) ]
   Change in stool short chain fatty acids levels as measured using gas chromatography with flame ionisation detection (GC-FID)
7. Change in urinary serotonin concentration [ Time Frame: Baseline and post-Phase 1A (weeks 8/9) ]
   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)
8. Change in salivary cortisol levels [ Time Frame: Baseline and post-Phase 1A (weeks 8/9) ]
   Change to salivary cortisol levels as measured using the Elecsys® Cortisol II assay

Eligibility Criteria

• Ages Eligible for Study: 5 Years to 12 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Australia, Queensland

University of Queensland, Child Health Research Centre

Brisbane, Queensland, Australia, 4001

Sponsors and Collaborators

The University of Queensland

Investigators

• Principal Investigator: Peter SW Davies, PhD; The University of Queensland

More Information

• Responsible Party: The University of Queensland
• ClinicalTrials.gov Identifier: NCT05151601
• Other Study ID Numbers: 2020-11-30-Auts
• First Posted: December 9, 2021
• Last Update Posted: February 15, 2023
• Last Verified: February 2023

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

Keywords provided by The University of Queensland:

Gut microbiome; Behaviour

Additional relevant MeSH terms:

Disease; Autistic Disorder; Autism Spectrum Disorder; Neurodevelopmental Disorders; Pathologic Processes; Child Development Disorders, Pervasive; Mental Disorders