Anxiety, Autism Spectrum Disorder, Neurodevelopmental Disorders
Conditions
Keywords
Gut microbiome, Behaviour
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.
Interventions
DIETARY_SUPPLEMENTExperimental
2 x sachets per day
OTHERPlacebo
2 x sachets per day
Sponsors
The University of Queensland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
5 Years to 12 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Behaviour change | 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. |
| Behaviour Change | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Anxiety Levels | 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. |
| Change in Quality of Life | 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. |
| Change in Stool Consistency | 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) |
| Change in GI Symptom Severity | 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. |
| Change in urinary serotonin concentration | 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) |
| Change in salivary cortisol levels | Baseline and post-Phase 1A (weeks 8/9) | Change to salivary cortisol levels as measured using the Elecsys® Cortisol II assay |
| Change in stool short chain fatty acids levels | 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) |
| Change in the Gut Microbiome | 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. |
Countries
Australia
Outcome results
None listed