Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000622707
Ethics application status
Approved
Date submitted
31/03/2022
Date registered
27/04/2022
Date last updated
25/07/2024
Date data sharing statement initially provided
27/04/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating the effect of fermented dairy on brain structure and function
Scientific title
Evaluating the effect of fermented dairy on brain imaging outcomes of healthy females: An eight week, randomised, placebo-controlled intervention study
Secondary ID [1] 306707 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mental health 325678 0
Condition category
Condition code
Mental Health 323024 323024 0 0
Anxiety
Mental Health 323025 323025 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will follow a randomised, placebo-controlled, double-blind, parallel groups design. Participants will be randomly assigned to two groups: one receiving a fermented dairy product (intervention) or a matched placebo (n = 20 per group). The participants will be required to consume 130g of the study intervention/placebo each morning for eight weeks. The intervention is a dairy milk beverage that has been fermented with >1 billion CFU of live active cultures (B. lactis (BB-12), S. Thermophilus, L. Bulgaricus). Participants will be asked to complete the consumption diary during the eight weeks and be requested to hand over the completed diary at the final visit.
Intervention code [1] 323153 0
Prevention
Intervention code [2] 323154 0
Lifestyle
Comparator / control treatment
Matched placebo
The placebo formula is also milk-based with the following added ingredients to match the appearance and flavour of the intervention: modified starch, lactic acid, citric acid, flavouring.
Control group
Placebo

Outcomes
Primary outcome [1] 329694 0
Differences in concentration of major brain metabolites (N-acetylaspartic acid, choline, creatine, myo-inositol, glutamate and glutamine) at left hippocampus measured by magnetic resonance spectroscopy between intervention and placebo groups.
Timepoint [1] 329694 0
8-weeks post-baseline
Secondary outcome [1] 403468 0
Differences in brain structural changes (including cortical thickness at whole-brain level and subcortical volumes) measured by magnetic resonance spectroscopy between intervention and placebo groups.
Timepoint [1] 403468 0
8-weeks post-baseline
Secondary outcome [2] 403469 0
Differences in functional (at rest) alteration at whole-brain level measured by magnetic resonance spectroscopy between intervention and placebo groups.
Timepoint [2] 403469 0
8-weeks post-baseline
Secondary outcome [3] 403470 0
Differences in functional activity during memory task measured by magnetic resonance spectroscopy between intervention and placebo groups.
Timepoint [3] 403470 0
8-weeks post-baseline
Secondary outcome [4] 403471 0
Differences in concentrations of oxidative stress (e.g. total antioxidant capacity) using blood samples between intervention and placebo groups.
Timepoint [4] 403471 0
8-weeks post-baseline
Secondary outcome [5] 407566 0
Differences in psychological symptoms of anxiety and depression using a 9-item Patient Health Questionnaire (PHQ-9)) between intervention and placebo groups.
Timepoint [5] 407566 0
8-weeks post-baseline
Secondary outcome [6] 407567 0
Differences in the functional potential of gut microbiome samples between intervention and placebo groups using whole-genome shot-gun metagenomic sequencing of stool samples.
Timepoint [6] 407567 0
8-weeks post-baseline.
Secondary outcome [7] 408543 0
Differences in structural connectivity alteration at whole-brain level measured by magnetic resonance spectroscopy between intervention and placebo groups.
Timepoint [7] 408543 0
8-week post baseline
Secondary outcome [8] 408544 0
Differences in concentrations of inflammatory markers (e.g. high sensitivity C-reactive protein) using blood samples between intervention and placebo groups.
Timepoint [8] 408544 0
8-week post baseline
Secondary outcome [9] 408545 0
Differences in concentrations of metabolites (e.g. GlycA) using blood samples between intervention and placebo groups.
Timepoint [9] 408545 0
8-week post baseline
Secondary outcome [10] 408546 0
Differences in quality of life (e.g. World Health Organization (WHO) WellBeing Index) between intervention and placebo groups.
Timepoint [10] 408546 0
8-week post baseline
Secondary outcome [11] 409104 0
Differences in gut microbiome composition between intervention and placebo groups using whole-genome shot-gun metagenomic sequencing of stool samples.
Timepoint [11] 409104 0
8-week post baseline

Eligibility
Key inclusion criteria
• Healthy females aged 18 – 55 years
• No cognitive impairment (MMSE score > 24)
• Absence of a major neurological disorder
• Absence of mood disturbance (BDI score >9)
• Absence of major gastrointestinal disorders (Irritable bowel syndrome, Crohn’s disease, etc.)
• Right handed
• Deemed safe and comfortable to undergo an MRI
• Willing to maintain their habitual diet and level of exercise
• Willing and able to comply with study procedures
• Able to provide voluntary informed consent
• English speaking or non-English speaking patients that can ensure external interpreter assistance (e.g. from a relative, spouse or friend) for the onsite clinical visits and for the phone follow-up timepoints.
Minimum age
18 Years
Maximum age
55 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• Use of probiotics or antibiotics in last 2 weeks (eligible following a 4-week washout/discontinuation period)
• Recently commenced a new supplement known to influence gut/brain health (eligible following a 4-week washout/discontinuation period)
• Consuming fermented dairy on a regular basis (eligible following a 4-week washout/discontinuation period)
• Unable or unlikely to attend the required study visits at the required timepoints or unable to complete the study protocol (e.g. upcoming travel, surgery)
• History of neurological illness or moderate – severe brain injury (i.e. no LOC, PTA or ongoing cognitive/neurological impairment),
• Allergy to dairy or lactose intolerance or allergy/intolerance to any study components
• Have a major unstable medical illness that is likely to impact on ability to adhere to study protocol or the study outcome measures
• Severe claustrophobia, non-MR compatible metallic implant , or other contraindication to MRI scanning,
• Lifetime diagnosis of learning difficulty, ADHD, or other condition involving cognitive impairment as a primary feature,
• Pregnancy or breastfeeding
• Sustained a head injury through TBI, concussion
• Participation in another study using an investigational product
• Left handed
• Pacemaker, aneurysm clip or anything that may interfere with the safety for MRI or quality of the images
• Any other reason that the investigator deems the individual unsuitable to be enrolled

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Computer-generated randomisation
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomly assigned to receive either an intervention or placebo using permuted block randomisation. Numbers assigned to each group will be equal on a 1:1 ratio. A third party, independent of the research team, will develop the computer-generated randomisation table utilising random block sizes and will be managed using REDCap (ResearchElectronic Data Capture).
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
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Statistical analysis of baseline characteristics comparing individuals in both conditions, will be performed using Student's t-test for normally distributed samples and Wilcoxon test for non-normally distributed samples, correlation analysis (Pearson and Spearman correlation coefficient) and linear regression models. Variables will be expressed as mean ± standard deviation (SD). Using intention to treat analysis, continuous outcome data will be analysed using linear regression models in order to compare treatment groups. Generalized estimation equation (GEE) approach with identity link assuming Normal distribution for the outcome will be implemented for all main and secondary analyses. The GEE model includes nominal time, nominal group allocation and the two-way interaction between time and group allocation. In this setting, the two-way interaction between time and group allocation estimates the between-group differential change from baseline to week 8 in the intervention vs. control group. An unstructured covariance pattern will be considered to account for within participants autocorrelation in time. Potential covariances will be included based on literature and also baseline demographic information.

Missing data will be imputed assuming missing not at random (MNAR) in intervention, control and both arms respectively and robustness of finding under different MNAR assumptions will be examined.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
30/05/2022
Actual
20/07/2022
Date of last participant enrolment
Anticipated
29/07/2022
Actual
19/10/2022
Date of last data collection
Anticipated
29/12/2022
Actual
21/12/2022
Sample size
Target
40
Accrual to date
Final
40
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 310243 0
Commercial sector/Industry
Name [1] 310243 0
Bega Dairy and Drinks Pty Ltd.
Country [1] 310243 0
Australia
Primary sponsor type
University
Name
Deakin University
Address
221 Burwood Highway
Burwood VIC 3125
Australia
Country
Australia
Secondary sponsor category [1] 312366 0
None
Name [1] 312366 0
Address [1] 312366 0
Country [1] 312366 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309922 0
Deakin University Human Research Ethics Review Committee
Ethics committee address [1] 309922 0
Ethics committee country [1] 309922 0
Australia
Date submitted for ethics approval [1] 309922 0
07/02/2022
Approval date [1] 309922 0
16/03/2022
Ethics approval number [1] 309922 0
2022-018

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

Contacts
Principal investigator
Name 115846 0
Prof Felice Jacka
Address 115846 0
Food & Mood Centre
Health Education Research Building (HERB)
Level 3, Rear of Kitchener House
285 Ryrie Street
Geelong, VIC 3220
Country 115846 0
Australia
Phone 115846 0
+61 03 4215 3302
Fax 115846 0
Email 115846 0
[email protected]
Contact person for public queries
Name 115847 0
Felice Jacka
Address 115847 0
Food & Mood Centre
Health Education Research Building (HERB)
Level 3, Rear of Kitchener House
285 Ryrie Street
Geelong, VIC 3220
Country 115847 0
Australia
Phone 115847 0
+61 03 4215 3302
Fax 115847 0
Email 115847 0
[email protected]
Contact person for scientific queries
Name 115848 0
Felice Jacka
Address 115848 0
Food & Mood Centre
Health Education Research Building (HERB)
Level 3, Rear of Kitchener House
285 Ryrie Street
Geelong, VIC 3220
Country 115848 0
Australia
Phone 115848 0
+61 03 4215 3302
Fax 115848 0
Email 115848 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Patient consent to sharing data for purposes beyond the trial was not sought at the time of HREC approval, therefore it is not possible to share IPD.


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
No additional documents have been identified.