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Trial registered on ANZCTR


Registration number
ACTRN12620000270910
Ethics application status
Approved
Date submitted
13/02/2020
Date registered
2/03/2020
Date last updated
2/03/2020
Date data sharing statement initially provided
2/03/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of Complex Milk Lipids on cognitive ageing
Scientific title
The effect of Complex Milk Lipids on cognitive function in older adults with Subjective Memory Complaints
Secondary ID [1] 300540 0
Nil known
Universal Trial Number (UTN)
U1111-1247-4211
Trial acronym
MIA (MIlk and Ageing)
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
Cognitive function 316253 0
Psychological wellness 316254 0
Biochemical Health 316255 0
Gut function 316256 0
Physical Health 316257 0
Mobility 316258 0
Condition category
Condition code
Mental Health 314541 314541 0 0
Studies of normal psychology, cognitive function and behaviour
Neurological 314542 314542 0 0
Studies of the normal brain and nervous system
Oral and Gastrointestinal 314543 314543 0 0
Normal oral and gastrointestinal development and function

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1: Low dose Complex Milk Lipids (CML)
Participants will be required to consume 2 x 25g serves of milk powder per day. Each serve is to be mixed with around 200ml water and can be consumed in two sittings or in a single sitting. Each daily dose contains roughly 10g of total CMLs. Participants consume the milk drink daily for 112 days. There are no specific requirements as to when participants consume their regular food relative to consumption of the milk drink.

Arm 2: High dose Complex Milk Lipids (CML)
Identical to Arm 1 except each daily dose contains roughly 25g of total CMLs.

Compliance will be monitored throughout the study. Participants will receive regular SMS/emails to monitor compliance including the number of intervention product serves missed in the preceding days. Participants will be assisted with this process through the completion of a consumption calendar that requires them to mark off each serving at time of its consumption. Participants who consume less than 80% of the required product in a given fortnight (equal to 6-or-more serves missed) will receive a courtesy call from the trial coordinator to problem solve compliance issues.
Intervention code [1] 316844 0
Treatment: Other
Comparator / control treatment
The trial interventions will be compared to a rice-starch placebo control. The active and control intervention products will be packaged in identical containers. Participants will be required to consume 2 x 25g serves of rice powder mixed with 200ml water per day in either two sittings or a single sitting.
Details of interventions found above in description of interventions (Arm 1; Arm 2).
Control group
Placebo

Outcomes
Primary outcome [1] 322865 0
The primary outcome of this study is to determine whether increased intake of complex milk lipids in older adults exerts beneficial effects on cognitive function as assessed by the Repeatable Battery of Neuropsychological Status (RBANS)
Timepoint [1] 322865 0
112 days after first dose of study treatment
Secondary outcome [1] 380047 0
Cognitive function assessed using the COMPASS cognitive testing battery (composite scores)
Timepoint [1] 380047 0
112 days after first dose of study treatment
Secondary outcome [2] 380048 0
Mood assessed using the Bond-Lader visual analogue scales
Timepoint [2] 380048 0
112 days after first dose of study treatment
Secondary outcome [3] 380049 0
Subjective memory complaints assessed using the Prospective and Retrospective Memory Questionnaire (PRMQ)
Timepoint [3] 380049 0
56 days and 112 days after first dose of study treatment
Secondary outcome [4] 380050 0
Psychological health assessed using the Depression and Anxiety Stress Scale (DASS-21)
Timepoint [4] 380050 0
56 days and 112 days after first dose of study treatment
Secondary outcome [5] 380051 0
Gut function assessed using the Gastrointestinal Symptom Rating Scale (GSRS)
Timepoint [5] 380051 0
56 days and 112 days after first dose of study treatment
Secondary outcome [6] 380052 0
Body composition assessed using Bioelectrical Impedance analysis (BIA)
Timepoint [6] 380052 0
112 days after first dose of study treatment
Secondary outcome [7] 380053 0
Mobility assessed using grip strength, the Short Physical Performance battery (SPPB), closed eye balancing and the sit and reach test
Timepoint [7] 380053 0
112 days after first dose of study treatment
Secondary outcome [8] 380054 0
Changes in brain structure assessed using Magnetic Resonance Imaging (MRI) (Swinburne site only)
Timepoint [8] 380054 0
112 days after first dose of study treatment
Secondary outcome [9] 380055 0
Changes in brain structure assessed using Magnetoencephalography (MEG) (Swinburne site only)
Timepoint [9] 380055 0
112 days after first dose of study treatment
Secondary outcome [10] 380056 0
Changes in brain function assessed using the n-back working memory task during MEG scan (Swinburne site only)
Timepoint [10] 380056 0
112 days after first dose of study treatment
Secondary outcome [11] 380057 0
Vital signs assessed using measures of blood pressure, body temperature and respiratory rate
Timepoint [11] 380057 0
112 days after first dose of study treatment
Secondary outcome [12] 380058 0
Blood glucose levels measured using haematological assessment of Haemoglobin A1C (HbA1C)
Timepoint [12] 380058 0
112 days after first dose of study treatment
Secondary outcome [13] 380059 0
Levels of Holotranscobalamin (Vitamin B12) in blood
Timepoint [13] 380059 0
112 days after first dose of study treatment
Secondary outcome [14] 380060 0
Levels of Brain Derived Neurotropic Factor (BDNF) measured in blood
Timepoint [14] 380060 0
112 days after first dose of study treatment
Secondary outcome [15] 380061 0
Inflammation measured using haematological assessments of cytokines: interleukin-1beta,
Timepoint [15] 380061 0
112 days after first dose of study treatment
Secondary outcome [16] 380062 0
Levels of homocysteine measured in blood
Timepoint [16] 380062 0
112 days after first dose of study treatment
Secondary outcome [17] 380063 0
Levels of Acetylcholine measured in blood
Timepoint [17] 380063 0
112 days after first dose of study treatment
Secondary outcome [18] 380064 0
Levels of Serotonin measured in blood
Timepoint [18] 380064 0
112 days after first dose of study treatment
Secondary outcome [19] 380065 0
Levels of y-Aminobutyric Acid (GABA) measured in blood
Timepoint [19] 380065 0
112 days after first dose of study treatment
Secondary outcome [20] 380066 0
Serum lipid levels
Timepoint [20] 380066 0
112 days after first dose of study treatment
Secondary outcome [21] 380315 0
Psychological health assessed using the Positive and Negative Affect Scale (PANAS)
Timepoint [21] 380315 0
56 days and 112 days after first dose of study treatment
Secondary outcome [22] 380316 0
Psychological health assessed using the Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS)
Timepoint [22] 380316 0
56 days and 112 days after first dose of study treatment
Secondary outcome [23] 380330 0
Inflammation measured using haematological assessments of cytokines: interleukin-6
Timepoint [23] 380330 0
112 days after first dose of study treatment
Secondary outcome [24] 380331 0
Inflammation measured using haematological assessments of cytokines: interleukin-10
Timepoint [24] 380331 0
112 days after first dose of study treatment
Secondary outcome [25] 380332 0
Inflammation measured using haematological assessments of cytokines: Interferon gamma
Timepoint [25] 380332 0
112 days after first dose of study treatment
Secondary outcome [26] 380333 0
Inflammation measured using haematological assessments of cytokines: Tumour Necrosis Factor alpha
Timepoint [26] 380333 0
112 days after first dose of study treatment

Eligibility
Key inclusion criteria
1. Males and females
2. Aged >55 & <76 years of age at clinic screen
3. Scores >25 on the subjective memory complaints questionnaire (MAC-Q)
4. BMI >18.5 or <35 at time of clinic screen
5. No Depression (indicated by scores <6 on the Geriatric Depression Scale (GDS-15)
Minimum age
55 Years
Maximum age
76 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Score of <22 on the MoCA
2. Previous adverse reaction to milk or dairy proteins
3. Allergy to rice
4. Any condition/event* where cognitive impairment may occur as determined by the PI (e.g., head injury, other brain trauma, transient ischemic attacks, stroke, coronary artery bypass surgery, heart surgery, degenerative neurological disease)
5. Previous diagnosis of Sleep Apnoea that remains untreated
6. Blood pressure >155 mmHg and diastolic >95 mmHg (unless applicant obtains letter from medical professional indicating fit for inclusion)
7. HbA1c >6.5% for non diabetics (=48mmol/mol), OR =7% (=53mmol/mol) if diagnosed with T2D and medically managed for at least 6-months
8. Type 1 Diabetes
9. Current smoker (or history of smoking including within last 12 months)
10. History of Intellectual Disability or other neurodevelopmental disorder (e.g., language disorder, ADHD, Autism)*
11. A mental health condition* that is being actively treated either pharmacologically or by a licensed mental-health professional
12. Participation in a study utilising the primary cognitive measures within the previous 12 months
13. Current or recent participation, within the last 30 days, in any other clinical trial involving the administration of an active intervention for any purpose.
* confirmed by trained Clinic Team Member; no clinical testing will be conducted to diagnose/confirm medical history

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)
The National Health & Medical Research Council (NHMRC) Clinical Trials Centre Central Randomisation Services using interactive voice response system (IVRS) will be engaged to implement independent randomisation for this study and treatment kit allocation. Following confirmation of eligibility and receipt of written consent, participants will be provided with a unique study identifier inclusive of the study site code. On attendance at the baseline visit, the PI (or designee) will telephone the automated NHMRC-IRVS and provide the participants study ID, sex, age, and MoCA score enabling the system to randomly assign the participant to an intervention condition whilst balancing groups on these key variables. The process will be stratified across study sites to ensure relatively equal proportions assigned to conditions across and within sites. If a participant withdraws from the study or is unable to complete the study for any reason after being randomised, their Study ID and intervention allocation will not be reissued to a new participant.

NHMRC will be responsible for the allocation and concealment of which group each participant is allocated to. Study staff at both sites will be blinded to group allocations.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Eligible participants will be assigned to interventions using stratified random assignment based on gender, age, MoCA score and study site. The randomisation scheme will be computer generated.
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
N/A
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Analysis of required sample size was based on detecting a simple repeated measures time x treatment interaction effect. Assuming a small effect size (f=.10), and a correlation between repeated measures of r=.60, estimates indicated that n=300 participants would provide 95% power at a significance level of a=.05. This effect size equates to a difference between two groups of approximately 3-IQ points on the RBans. Further models allowing for up to a 20% attrition (n=240 study completors) indicate sufficient power is retained (ß=88%, a=.05) for an effect of the same magnitude (f=.10).
There are no planned interim analyses of any study outcomes. Therefore, a full statistical analysis plan will be developed prior to completion of the study in consultation with the independent statistician appointed by the trial sponsor. The analysis plan will detail intention for both primary and secondary outcomes. It is envisaged that analysis will focus on generalised linear mixed models. Outcomes will be assessed at the Intention-To-Treat-level, with sensitivity models conducted using the per-protocol sample. Outcomes to be compared between the study groups include cognitive performance, psychological wellness, mobility and biochemical outcomes. The primary analyses will involve 3-way comparisons between the two MFGM+ groups and the placebo control group.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment postcode(s) [1] 29328 0
3122 - Hawthorn
Recruitment postcode(s) [2] 29329 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 304954 0
Commercial sector/Industry
Name [1] 304954 0
Fonterra
Address [1] 304954 0
Fonterra Research and Development Centre, Dairy Farm Rd, Fitzherbert, Palmerston North, 4472 New Zealand
Country [1] 304954 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
Fonterra
Address
Fonterra Research and Development Centre, Dairy Farm Rd, Fitzherbert, Palmerston North, 4472 New Zealand
Country
New Zealand
Secondary sponsor category [1] 305311 0
Government body
Name [1] 305311 0
CSIRO
Address [1] 305311 0
SAHMRI (South Australian Health and Medical Research Institute), North Terrace, Adelaide, South Australia 5000
Country [1] 305311 0
Australia
Other collaborator category [1] 281192 0
University
Name [1] 281192 0
Swinburne University of Technology
Address [1] 281192 0
PO Box 218, Hawthorn, VIC 3122
Country [1] 281192 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305362 0
CSIRO Health and Medical Human Research Ethics Committee
Ethics committee address [1] 305362 0
Ecosciences Precinct, Dutton Park QLD 4102 GPO BOX 2583, Brisbane QLD 4001, Australia
Ethics committee country [1] 305362 0
Australia
Date submitted for ethics approval [1] 305362 0
10/09/2019
Approval date [1] 305362 0
13/11/2019
Ethics approval number [1] 305362 0
2019_076_HREC
Ethics committee name [2] 305364 0
Swinburne University Human Research Ethics Committee
Ethics committee address [2] 305364 0
Research Ethics, Integrity and Biosafety office, Swinburne Research (H68), PO Box 218, Hawthorn, VIC 3122
Ethics committee country [2] 305364 0
Australia
Date submitted for ethics approval [2] 305364 0
29/11/2019
Approval date [2] 305364 0
29/11/2019
Ethics approval number [2] 305364 0
20191542-3119

Summary
Brief summary
The aim of the present study is to investigate the effects of Complex Milk Lipids on cognitive function and other health-related outcomes—including physical health, psychological wellbeing and blood biomarkers—in ageing adults 55-to-75 years of age. Ingredients developed by the principal trial sponsor contain higher levels of milk phospholipids and gangliosides (complex lipids) and may have the potential to produce benefits on these outcomes. This will be a 16-week randomised, double-blind placebo-controlled trial where 300 participants will be recruited across the CSIRO and Swinburne University sites. The trial will consist of three intervention arms: 1) Low dose milk drink delivering ~10g of total CMLs; 2) High dose milk drink delivering 25g of total CMLs; and 3) Rice starch placebo control
Trial website
CSIRO Adelaide
https://www.csiro.au/en/Research/Health/Nutrition-and-health-research-clinic/Current-studies/Participate-in-a-study
Trial related presentations / publications
N/A
Public notes

Contacts
Principal investigator
Name 100122 0
Dr Ian Zajac
Address 100122 0
Research Scientist/Psychologist
Nutrition and Health Program, CSIRO
PO Box 10041, Adelaide BC, SA, 5000
Country 100122 0
Australia
Phone 100122 0
+61 8 8303 8875
Fax 100122 0
Email 100122 0
Ian.Zajac@csiro.au
Contact person for public queries
Name 100123 0
Dr Ian Zajac
Address 100123 0
Research Scientist/Psychologist
Nutrition and Health Program, CSIRO
PO Box 10041, Adelaide BC, SA, 5000
Country 100123 0
Australia
Phone 100123 0
+61 8 8303 8875
Fax 100123 0
Email 100123 0
Ian.Zajac@csiro.au
Contact person for scientific queries
Name 100124 0
Dr Ian Zajac
Address 100124 0
Research Scientist/Psychologist
Nutrition and Health Program, CSIRO
PO Box 10041, Adelaide BC, SA, 5000
Country 100124 0
Australia
Phone 100124 0
+61 8 8303 8875
Fax 100124 0
Email 100124 0
Ian.Zajac@csiro.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No IPD sharing has been approved under the ethics approval for this study
What supporting documents are/will be available?
No other documents available
Summary results
No Results