Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618002023235
Ethics application status
Approved
Date submitted
4/12/2018
Date registered
17/12/2018
Date last updated
3/02/2023
Date data sharing statement initially provided
17/12/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The Moo'D Study: A randomised controlled trial of A2 vs conventional dairy products in women with low mood.
Scientific title
A randomised controlled trial of A2 vs conventional dairy products in women with low mood.
Secondary ID [1] 295518 0
Nil known
Universal Trial Number (UTN)
Trial acronym
The Moo'D Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Psychological distress 308727 0
Condition category
Condition code
Mental Health 307666 307666 0 0
Depression
Mental Health 307719 307719 0 0
Anxiety
Mental Health 307720 307720 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a triple-blinded, 16-week, 1:1 parallel-group, randomised controlled trial. Women aged 18-75 years with low mood will be randomised to receive either A2 dairy products (A2 skim milk + A2 full fat cheddar cheese) or conventional dairy products (conventional skim milk + conventional full fat cheddar cheese). Participants will be provided with all study products, supplied by The a2 Milk Company, which are to replace usual amounts of dairy products consumed within the diet. Each day for 16 weeks, all participants are to consume at least 250ml of the study milk and the study cheese ad libitum.

The study products will be nutritionally equivalent with the exception of beta-casein content. Conventional dairy products will contain both A1 and A2 beta-casein protein whereas A2 dairy products will contain only A2 beta-casein. Participants are to refrain from consuming all other cow’s milk products throughout the intervention, with the exception of goat and sheep’s yoghurt. Dairy diaries will be provided to participants to facilitate the completion of fortnightly online questionnaires, which will be used to monitor dietary adherence.

The intervention will be delivered by investigators with expertise in food science, and casual research assistants who will be employed as required. Individual study assessments will take place in clinic at University Hospital Geelong at baseline, week 4 and week 16.

At baseline (part A), participants will complete a series of online questionnaires online with a researcher and be mailed out a stool collection kit. Within one week of baseline (part A), the participant will visit the clinic (part B) to return their collected stool sample, provide a blood sample and undergo a cognitive assessment. Participants will receive instructions regarding their dietary prescription and receive their allocated dairy products.

At week 4 (approx. 20 minutes), participants will meet with study investigators to return completed stool samples, provide a blood sample and collect additional dairy products.

At week 16 (approx. 2 hours), participants will return completed stool samples, complete a series of questionnaires, provide a blood sample and undergo a cognitive assessment and body composition scan. If required, participants will also attend the clinic at week 10 to collect additional dairy products.

At fortnightly intervals throughout the intervention, participants will complete a series of online questionnaires at home pertaining to primary and secondary outcomes of this study.
Intervention code [1] 301784 0
Lifestyle
Intervention code [2] 312632 0
Treatment: Other
Comparator / control treatment
Participants allocated to the control group will consume conventional dairy products (conventional skim milk + conventional full fat cheese) in amounts prescribed above. Control products will also be supplied by The a2 Milk Company. Control participants will complete the assessment schedule, as per the intervention group.
Control group
Active

Outcomes
Primary outcome [1] 306653 0
Symptoms of psychological distress (depression, anxiety and stress) as measured by the Depression Anxiety Stress Scale-21 (DASS- 21) total score.
Timepoint [1] 306653 0
Baseline (week 0) and every two weeks after that (weeks 2, 4, 6, 8, 10, 12, 14, 16).
Secondary outcome [1] 349132 0
Symptoms of depression, anxiety and stress measured by DASS-21 sub-scale scores.
Timepoint [1] 349132 0
Baseline (week 0) and every two weeks after that (weeks 2, 4, 6, 8, 10, 12, 14, 16).
Secondary outcome [2] 349137 0
Changes in severity of depression measured by the 8-item Patient Health Questionnaire (PHQ-8).
Timepoint [2] 349137 0
Baseline (week 0) and every two weeks after that (weeks 2, 4, 6, 8, 10, 12, 14, 16).
Secondary outcome [3] 349139 0
Functional gastrointestinal disorders diagnosed by the Rome IV Bowel Disorders and Central Nervous System Disorders of GI Pain Module questionnaire (Q40-67 of the Rome IV Diagnostic Questionnaire for Functional Gastrointestinal Disorders in Adults)

Timepoint [3] 349139 0
Baseline (week 0) and week 16
Secondary outcome [4] 349140 0
Gut symptoms measured by the Visual Analogue Scale for IBS (VAS-IBS)
Timepoint [4] 349140 0
Baseline (week 0) and every two weeks after that (weeks 2, 4, 6, 8, 10, 12, 14, 16).
Secondary outcome [5] 349141 0
Stool formation measured by the Bristol Stool Form Scale questionnaire (BSFQ)
Timepoint [5] 349141 0
Baseline (week 0) and every two weeks after that (weeks 2, 4, 6, 8, 10, 12, 14, 16).
Secondary outcome [6] 349142 0
Gut microbiome composition will be measured in stool via 16S rRNA gene sequencing.

Subject to funding, stool samples may be sent for meta-genomics analysis, an advanced and more in depth analysis technique for assessing microbial parameters.
Timepoint [6] 349142 0
Baseline (week 0), week 4 and week 16
Secondary outcome [7] 349143 0
Body composition measured by total body dual-energy X-ray absorptiometry (DXA) scan.
Timepoint [7] 349143 0
Baseline (week 0) and week 16
Secondary outcome [8] 349144 0
Perceived well-being will be assessed with the 5-item World Health Organisation Well-Being Index (WHO-5).
Timepoint [8] 349144 0
Baseline (week 0) and week 16
Secondary outcome [9] 349145 0
Quality of life will be measured by the Assessment of Quality of Life (AQoL)-8D instrument. The 35 items may be reduced to a single utility score using the AQoL-8D algorithm, to reflect health related well-being.
Timepoint [9] 349145 0
Baseline (week 0) and week 16
Secondary outcome [10] 349147 0
8-item Athens Insomnia Scale will be used as a composite measure of sleep difficulty, quality and duration.
Timepoint [10] 349147 0
Baseline (week 0) and week 16
Secondary outcome [11] 349148 0
Cognitive performance will be measured using a computerised cognitive battery (Cogstate). Tasks will measure: Paired Associate Learning (Continuous Paired Associate Learning), Working Memory (One Back), Visual Learning (One Card), Psychomotor Function (Detection) and Attention (Identification).
Timepoint [11] 349148 0
Baseline (week 0) and week 16
Secondary outcome [12] 349149 0
Metabolite profiling to measure systemic metabolites including beta-casomorphin-7 (BCM-7) concentration in plasma.
Timepoint [12] 349149 0
Baseline (week 0), week 4 and week 16
Secondary outcome [13] 349150 0
Markers of leaky gut (sCD14 and LBP) will be measured in plasma.
Timepoint [13] 349150 0
Baseline (week 0), week 4 and week 16
Secondary outcome [14] 349347 0
Oxidative stress measured by plasma glutathione (GSH) concentrations.
Timepoint [14] 349347 0
Baseline (week 0), week 4 and week 16
Secondary outcome [15] 349349 0
Resource utilisation will be determined through completion of a Resource Use questionnaire.
Timepoint [15] 349349 0
Baseline (week 0) and week 16
Secondary outcome [16] 352836 0
Change in inflammation as indicated by markers such as Tumour Necrosis Factor alpha (TNF-alpha), Interleukin-1 (IL-1), Interleukin-6 (IL-6), via a blood plasma assay.
Timepoint [16] 352836 0
Baseline (week 0), week 4 and week 16
Secondary outcome [17] 352837 0
Change in gut inflammation as measured by markers such as IL-4 and humoral immune markers (IgE, IgG).
Timepoint [17] 352837 0
Baseline (week 0), week 4 and week 16
Secondary outcome [18] 354707 0
Short chain fatty acid (SCFA) concentrations in stool may also be measured, subject to funding.
Timepoint [18] 354707 0
Week 0, 4, 16

Eligibility
Key inclusion criteria
Female participants with low mood as determined by a PHQ-8 score of 5 or higher at baseline.
Current conventional milk consumption of at least 250ml/day.
Willingness to commit to consuming only dairy products provided by the study.
Available for intervention duration.
Able to understand study materials and directions, in English.
Must have access to internet and a computer/smartphone/tablet.
Be willing to comply with all requirements and procedures of the study.
Agree not to enrol in another interventional clinical research trial while part of the study.
Minimum age
18 Years
Maximum age
75 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Current consumer of A2 dairy products.
Cow’s milk (dairy) allergy (established diagnosis).
Lactose intolerance (established diagnosis).
Pregnant, planning to become pregnant, or lactating.
History of dementia and/or stroke.
Diagnosed with or commenced new treatment for, anxiety and/or depression, within 1 month prior to baseline.
Gastrointestinal (GI) diseases or past major GI surgery likely to interfere with study outcomes (e.g. ulcerative colitis, crohn's disease, faecal impaction, coeliac disease, hemi colectomy, ileostomy, and colostomy).
Regular use of: morphine/opioid-based medications, recreational/illicit drugs,
Antibiotic use within 1 month prior to baseline.

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)
A random unique three character alphanumeric study kit code (e.g. KL5, ZA1, CJ8) will be allocated to each participant at randomisation from ‘study kit’ allocation lists; one for each stratum. The kit code will correspond with a pre-packaged kit consisting of milk and cheese. A research assistant who is not involved in any other aspect of the study will make up study kits according to the allocation lists and label each with the appropriate kit code.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomly assigned to receive A2 dairy products (A, intervention) or conventional dairy products (B, control) using stratified permuted block randomisation. Numbers assigned to each group will be equal on a 1:1 ratio. Four strata will be constructed based on two variables; age (18-49; 50-75) and mood (PHQ-8 scores: 5-14; 15-24). A third party, independent of the research team, will develop the computer-generated randomisation table utilising random block sizes and partitioned by stratum.
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
An achievable sample size of 80 (40 per arm) has been calculated to detect a between-group mean difference of 2.3 or greater difference in DASS21 total score from baseline to 16 weeks follow-up between the intervention and control groups. This is equivalent to an effect size (e.g. the standardised mean change from baseline value between the two groups) of 0.63 (moderate effect size). We assume standard deviation of DASS21 score change is 3.6 from similar published RCTs. A sample size of 80 (40 in each arm) achieves 80% power for a two-tailed analysis with type I level of 0.05. The total sample size will need to be inflated to 90 to account for an anticipated attrition rate of 12.5%. If our attrition rate is higher than anticipated (e.g. due to COVID-19 pandemic), we will aim to recruit further participants.

All randomised participants with valid 0 and 16-week observations will be included in the primary analysis (modified Intent-To-Treat analysis). To examine the primary hypothesis, we will use generalised estimating equation (GEE), using an identity link function and normal distribution, to test the between-group differential change in DASS-21 total score from baseline to 16 weeks follow-up between the intervention and control groups.

The secondary continuous outcome measures will be analysed using the same approach as the primary outcome. Dichotomous data will be presented as proportions, with 95% confidence interval, and reporting Chi-square or Fisher’s exact p-value where appropriate. Likelihood based generalised linear mixed repeated measures approach (GLMRM) with logit link will be used to compare dichotomous outcomes.

In addition to primary and secondary outcomes the following covariate data will be captured; participant age, height, weight, waist and hip circumference, past medical history, medication and dietary supplement usage, personality disorders (using The Standardised Assessment of Personality Abbreviated Scale), dietary intake (using Dietary Questionnaire for Epidemiological Studies v3.2) and level of physical activity (using International Physical Activity Questionnaire - Short Form). Potential covariates will be introduced into the analysis as appropriate to control for variables.

Future analyses will examine associations between key variables using all baseline data. This work will be independent to the main trial report and will be conducted subject to further funding and staff resourcing.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
7/01/2019
Actual
22/01/2019
Date of last participant enrolment
Anticipated
1/05/2022
Actual
16/06/2021
Date of last data collection
Anticipated
1/09/2022
Actual
8/10/2021
Sample size
Target
90
Accrual to date
Final
74
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 12142 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment postcode(s) [1] 23384 0
3220 - Geelong

Funding & Sponsors
Funding source category [1] 300043 0
University
Name [1] 300043 0
Deakin University
Country [1] 300043 0
Australia
Funding source category [2] 300103 0
Commercial sector/Industry
Name [2] 300103 0
The a2 Milk Company Limited
Country [2] 300103 0
Australia
Primary sponsor type
University
Name
Deakin University
Address
Human Research Ethics Office
Deakin Research Integrity
Deakin University
221 Burwood Hwy
Burwood, VIC 3125
Country
Australia
Secondary sponsor category [1] 301060 0
None
Name [1] 301060 0
Address [1] 301060 0
Country [1] 301060 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300911 0
Barwon Health Human Research Ethics Committee
Ethics committee address [1] 300911 0
Ethics committee country [1] 300911 0
Australia
Date submitted for ethics approval [1] 300911 0
29/11/2017
Approval date [1] 300911 0
13/12/2017
Ethics approval number [1] 300911 0
17/169
Ethics committee name [2] 300948 0
Deakin University Human Research Ethics Committee
Ethics committee address [2] 300948 0
Ethics committee country [2] 300948 0
Australia
Date submitted for ethics approval [2] 300948 0
05/07/2018
Approval date [2] 300948 0
12/07/2018
Ethics approval number [2] 300948 0
2018-234

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

Contacts
Principal investigator
Name 85174 0
Prof Felice N Jacka
Address 85174 0
Food & Mood Centre, Deakin University
285 Ryrie Street
P.O. Box 281
Geelong
VIC 3220
Country 85174 0
Australia
Phone 85174 0
+61 422 194 218
Fax 85174 0
Email 85174 0
[email protected]
Contact person for public queries
Name 85175 0
Rachel Fiddes
Address 85175 0
Food & Mood Centre, Deakin University
285 Ryrie Street
P.O. Box 281
Geelong
VIC 3220
Country 85175 0
Australia
Phone 85175 0
+61 0435948387
Fax 85175 0
Email 85175 0
[email protected]
Contact person for scientific queries
Name 85176 0
Felice N Jacka
Address 85176 0
Food & Mood Centre, Deakin University
285 Ryrie Street
P.O. Box 281
Geelong
VIC 3220
Country 85176 0
Australia
Phone 85176 0
+61 422 194 218
Fax 85176 0
Email 85176 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?
All of the individual participant data collected during the trial, after de-identification.
When will data be available (start and end dates)?
Immediately following publication. No end date.
Available to whom?
Investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose.
Available for what types of analyses?
Any purpose.
How or where can data be obtained?
Proposals should be directed to [email protected]


What supporting documents are/will be available?




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.