Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617000795392
Ethics application status
Approved
Date submitted
16/05/2017
Date registered
31/05/2017
Date last updated
27/02/2023
Date data sharing statement initially provided
16/10/2019
Date results provided
27/02/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised controlled trial of the effects of dietary prebiotic foods and probiotic supplements on adult mental health and cognition: The "Gut Feelings" trial
Scientific title
A randomised controlled trial of the effects of dietary prebiotic foods and probiotic supplements on mental health and cognition in adults with subclinical depression and/or anxiety: The "Gut Feelings" trial
Secondary ID [1] 291710 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Depression 302888 0
Anxiety 302889 0
Stress 302890 0
Condition category
Condition code
Mental Health 302371 302371 0 0
Studies of normal psychology, cognitive function and behaviour
Mental Health 302789 302789 0 0
Depression
Mental Health 302790 302790 0 0
Anxiety

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Group A (probiotic group; 8-week duration): Twice-daily oral capsule of Bioceuticals MoodBiotic, containing 8 probiotic strains delivering 12 billion colony forming units (CFUs) + no change to existing diet. Each oral capsule will contain the following probiotic strains:
Bifidobacterium bifidum (Bb-06): 2 billion colony forming units (CFU)
Bifidobacterium animalis subsp. lactis: 1 billion CFU
Bifidobacterium longum (Rosell-175): 1 billion CFU
Lactobacillus acidophilus (La-14): 2 billion CFU
Lactobacillus helveticus (Rosell-52): 2 billion CFU
Lactobacillus casei (Lc-11): 2 billion CFU
Lactobacillus plantarum (Lp-115): 1 billion CFU
Lactobacillus rhamnosus (HN001): 1 billion CFU

Group B (prebiotic group; 8-week duration): High-prebiotic diet + twice-daily oral placebo (inactive) capsule. Dietary intervention involves eating 7 or more serves of prebiotic-rich foods per day. Prebiotic-rich foods are plant foods containing relatively high levels of fructans and/or galactooligosaccharides, as reported in the food-science literature. Some examples are asparagus, garlic, onion, oats, whole wheat, chickpeas, and watermelon. The remainder of the diet is subject to the participant's discretion. An online educational video (8-minute duration), prepared and delivered by an Accredited Practising Dietitian/nutrition lecturer will be shown to participants at their baseline session and a hard-copy handout provided. Content of video/handout: information on the high-prebiotic diet, suitable foods and how to introduce them into the diet, and recipe suggestions. The video and handout were specifically designed for the current study. Participants are responsible for purchasing and incorporating high-prebiotic foods into their diet. A hamper of shelf-stable high-prebiotic foods will be provided to participants at baseline, as a 'starter kit'.

Group C (synbiotic group; 8-week duration): Combination of Group A (twice-daily oral probiotic capsule) + Group B (high-prebiotic diet) interventions

For all groups, supplement compliance will be measured by returned capsule count at 8-weeks. Adherence to allocated diet will be measured by completion of a purpose-built online dietary screener at Weeks 0, 2, 4, 6, and 8.
Intervention code [1] 297792 0
Treatment: Other
Comparator / control treatment
Group D (placebo group; 8-week duration): Twice-daily oral placebo (inactive) capsule + no change to existing diet

Supplement compliance will be measured by returned capsule count at 8-weeks. Adherence to existing diet will be measured by completion of a purpose-built online dietary screener at Weeks 0, 2, 4, 6, and 8.
Control group
Placebo

Outcomes
Primary outcome [1] 301945 0
Psychological distress (POMS 2-SF total score)
Timepoint [1] 301945 0
Baseline, 2-weeks, 4-weeks, 6-weeks, 8-weeks, 20-weeks
Secondary outcome [1] 334324 0
Depression (BDI-II)
Timepoint [1] 334324 0
Baseline, 8-weeks
Secondary outcome [2] 334325 0
Anxiety (BAI)
Timepoint [2] 334325 0
Baseline, 8-weeks
Secondary outcome [3] 334326 0
Stress (PSS)
Timepoint [3] 334326 0
Baseline, 8-weeks
Secondary outcome [4] 334327 0
Diet quality (CNAQ)
Timepoint [4] 334327 0
Baseline, 8-weeks
Secondary outcome [5] 334328 0
Health-related quality of life (SF-36)
Timepoint [5] 334328 0
Baseline, 8-weeks
Secondary outcome [6] 334329 0
Well-being (WHO-5)
Timepoint [6] 334329 0
Baseline, 8-weeks
Secondary outcome [7] 334330 0
Cognition (processing speed, attention, learning, working memory) (Cogstate Brief Battery)
Timepoint [7] 334330 0
Baseline, 8-weeks
Secondary outcome [8] 334331 0
Sleep (LSEQ)
Timepoint [8] 334331 0
Baseline, 8-weeks
Secondary outcome [9] 334332 0
Bowel health (ROME IV)
Timepoint [9] 334332 0
Baseline, 8-weeks
Secondary outcome [10] 334333 0
16S rRNA stool sequencing
Timepoint [10] 334333 0
Baseline, 8-weeks
Secondary outcome [11] 335159 0
Polyphenol intake (Phenol-explorer 3.6)
Timepoint [11] 335159 0
Baseline, 8-weeks

Eligibility
Key inclusion criteria
- Prebiotic fibre intake of <3 grams/day, as measured by a purpose-built Dietary Screener, to ensure that there is sufficient scope for improvement in diet
- Subclinical levels of anxiety and/or depression. Eligible participants must score 16-26 on the Kessler Psychological Distress Scale (K10)
- Free of psychiatric medications for > 4 weeks
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Ingestion of fermented foods or probiotic supplements within past 2 weeks
- Substance dependence within the previous month
- BMI over 35
- Fulfils diagnostic criteria for a clinical mental illness
- Currently taking medication with primarily CNS activity
- Pregnancy
- Irritable bowel syndrome or chronic constipation, and FODMAP-sensitive individuals
- Taking antibiotics, proton pump inhibitors, non-steroid anti-inflammatory drugs (any amount greater than 3 doses per month), or immunocompromising medication

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The probiotic and placebo supplement capsules are identical in appearance. Bottles of capsules will be numbered clearly by a disinterested third party. The key linking pack numbers to treatment arms will be maintained by a disinterested third party.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Pack number allocation to a treatment arm will be randomly assigned using permuted block randomisation. Two treatment arms will involve the dietary intervention, and the other two will require no change to diet. A disinterested third party will develop the computer-generated randomisation plan. Trial personnel will allocate packs sequentially, and packs are identical so as to conceal treatment allocation and maintain blinding.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Factorial
Other design features
The supplement component will be double-bllinded
The dietary intervention component will be single blinded (participants are aware of which diet they are consuming)
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
We will recruit a sample size of 128 participants (32 participants in each arm). The study is powered to detect a potential small to moderate difference between the treatment and placebo groups. Based on a two-tailed analysis with alpha=0.05, beta=0.80, and a critical F(3,124) of 2.68, 128 participants are required in total (Cohen’s d effect size of 0.30 or greater). Based on previous nutraceutical RCTs, attrition at the rate of 15% is expected, and to manage this, intention-to-treat analysis will be employed.

Data will be analysed using SPSS 22.0. Analysis of data will be conducted with blinding to group allocations. The primary efficacy analysis will assess average treatment group differences for the primary outcome measure (POMS total score) over the entire study period and use a likelihood-based mixed-effects model, repeated measures approach (MMRM). Results from the analysis of dichotomous data (e.g. demographics and genetic data) will be presented as proportions (e.g. Relative Risks), with 95% confidence interval, and Fisher’s Exact p-value where appropriate. Non-parametric statistics will be used when assumptions for parametric methods are violated. Cohen’s d effect sizes will be calculated. All tests of treatment effects will be conducted using a two-sided alpha level of 0.05 and 95% confidence intervals. Dose-response effects associated with intervention adherence will be explored utilising moderation analysis via SPSS Hayes PROCESS Macro Model 1. Mediation hypotheses will be assessed via SPSS Hayes PROCESS Macro Model 4.

Statistical analysis regarding the gut microbiota composition will include the following:
- Alpha and beta diversity between groups at baseline and following 8-week prebiotic, probiotic and synbiotic interventions in adults.
- Differential abundance testing using a tool such as DESeq2
- Path analysis to test the hypothesis that characteristics of microbiota composition mediate the relationship between diet quality and mental health symptoms.
- Clustering techniques such as principle components analysis and K-Means will be employed to identify gut microbiome subgroups at baseline that predict response to each of the three intervention types.
- Partial least squares discriminant analysis and/or machine learning techniques will then be used to identify specific bacterial taxa following the intervention whose abundance is strongly predictive of intervention group, or response to intervention/s.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
19/06/2017
Actual
16/01/2018
Date of last participant enrolment
Anticipated
30/06/2019
Actual
17/04/2019
Date of last data collection
Anticipated
30/11/2019
Actual
17/09/2019
Sample size
Target
128
Accrual to date
Final
119
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 7927 0
The Melbourne Clinic - Richmond
Recruitment postcode(s) [1] 15887 0
3121 - Richmond

Funding & Sponsors
Funding source category [1] 296210 0
University
Name [1] 296210 0
The University of Melbourne
Country [1] 296210 0
Australia
Funding source category [2] 296542 0
Commercial sector/Industry
Name [2] 296542 0
Bioceuticals
Country [2] 296542 0
Australia
Funding source category [3] 296545 0
Commercial sector/Industry
Name [3] 296545 0
Uncle Toby's
Country [3] 296545 0
Australia
Funding source category [4] 296546 0
Commercial sector/Industry
Name [4] 296546 0
The Healthy Grain
Country [4] 296546 0
Australia
Funding source category [5] 296547 0
Commercial sector/Industry
Name [5] 296547 0
McKenzie's Foods
Country [5] 296547 0
Australia
Funding source category [6] 296548 0
Commercial sector/Industry
Name [6] 296548 0
Sanitarium
Country [6] 296548 0
Australia
Funding source category [7] 296549 0
Commercial sector/Industry
Name [7] 296549 0
Real Foods
Country [7] 296549 0
Australia
Primary sponsor type
University
Name
The University of Melbourne
Address
The University of Melbourne
VIC 3010
Country
Australia
Secondary sponsor category [1] 295498 0
None
Name [1] 295498 0
Address [1] 295498 0
Country [1] 295498 0
Other collaborator category [1] 280136 0
Charities/Societies/Foundations
Name [1] 280136 0
Food and Mood Centre
Address [1] 280136 0
Food & Mood Centre, IMPACT Strategic Research Centre
School of Medicine, Deakin University
Health Education and Research Building (HERB)
Level 3, University Hospital Geelong
285 Ryrie Street, Geelong VIC 3220
Country [1] 280136 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297449 0
The Melbourne Clinic Research Ethics Committee
Ethics committee address [1] 297449 0
Ethics committee country [1] 297449 0
Australia
Date submitted for ethics approval [1] 297449 0
23/11/2016
Approval date [1] 297449 0
02/05/2017
Ethics approval number [1] 297449 0
Project 289

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 74070 0
Prof Jerome Sarris
Address 74070 0
Prof Jerome Sarris
Western Sydney University
Locke Bag 1797
Penrith NSW 2751
Country 74070 0
Australia
Phone 74070 0
+61 2 46203326
Fax 74070 0
Email 74070 0
[email protected]
Contact person for public queries
Name 74071 0
Tanya Marie Freijy
Address 74071 0
The Melbourne Clinic Professorial Unit
2 Salisbury St
Richmond VIC 3121
Country 74071 0
Australia
Phone 74071 0
+61 3 9487 4748
Fax 74071 0
Email 74071 0
[email protected]
Contact person for scientific queries
Name 74072 0
Jerome Sarris
Address 74072 0
Prof Jerome Sarris
Western Sydney University
Locke Bag 1797
Penrith NSW 2751
Country 74072 0
Australia
Phone 74072 0
+61 2 46203326
Fax 74072 0
Email 74072 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual participant data underlying published results
When will data be available (start and end dates)?
Upon publication with no end date
Available to whom?
Anyone who wishes to access it
Available for what types of analyses?
Any purpose
How or where can data be obtained?
Publishing journals will provide an online link to OSF database in the article data availability statement


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseEffects of a high-prebiotic diet versus probiotic supplements versus synbiotics on adult mental health: The "Gut Feelings" randomised controlled trial.2023https://dx.doi.org/10.3389/fnins.2022.1097278
N.B. These documents automatically identified may not have been verified by the study sponsor.