Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613000347763
Ethics application status
Approved
Date submitted
22/03/2013
Date registered
2/04/2013
Date last updated
18/07/2019
Date data sharing statement initially provided
18/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The Neurocognitive effects of Lacprodan(Registered Trademark) PL-20 in elderly participants with age-associated memory impairment.
Scientific title
A randomised placebo-controlled clinical trial investigating the neurocognitive effects and in vivo mechanisms of action of Lacprodan(Registered Trademark) PL-20 in elderly participants with age-associated memory impairment.
Secondary ID [1] 282166 0
Nil known
Universal Trial Number (UTN)
U1111-1140-9332
Trial acronym
PLICAR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Age-associated Memory Impairment (AAMI) 288672 0
Condition category
Condition code
Mental Health 289023 289023 0 0
Studies of normal psychology, cognitive function and behaviour

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Lacprodan(Registered Trademark) PL-20 is a fat-reduced cream powder manufactured by Arla Foods Ingredients P/S, Denmark. In comparison to regular cream powder Lacprodan(Registered Trademark) PL-20 is enriched in protein and phospholipids, while its triglyceride and lactose content is reduced.

Lacprodan(Registered Trademark) PL-20 will be administered orally at a maximum dose of 16g/day, providing minimum daily dosages of 2.7g total phospholipids and 300mg phosphatidylserine (PS). Lacprodan will be administered as a powder dissolved in <=250mL water and drunk once per day with breakfast for 180 days (6 moinths).

The Phospholipid composition of Lacprodan(Registered Trademark) PL-20 is as follows: (Percentages(%) and minimum dosages per 16g)

Shingomyelin 4.3% 688 mg
Phosphatidyl choline (PC) 4.3% 688 mg
Phosphatidyl serine (PS) 1.9% 304 mg
Phosphatidyl ethanolamine (PE) 3.5% 560 mg
Phosphatidyl inositol (PI) 1.3% 208 mg
Gangliosides and others 0.7% 112 mg

Treatment compliance will be monitored by the use of a compliance log which participants will take home with them and record the time at which they consume the drinks every day. If for some reason they miss a dose, they will be instructed to make a note of this in the log. In addition to the compliance log, participants will also be required to return all unused sachets at the completion of the study so that the experimenter can confirm that the number of sachets they have taken is in agreement with their log.
Intervention code [1] 286774 0
Treatment: Other
Comparator / control treatment
Two placebo treatments will be administered: (i) an inert placebo consisting of rice starch (20g/day) and (ii) a milk protein concentrate (12g/day, also manufactured by Arla Foods Ingredients) that has no phospholipid content. Both placebo treatments will be administered orally as powders dissolved in less than or equal to 250mL water and consumed once per day with breakfast for 180 days (6 months). Both placebo treatments will be matched to Lacprodan (Registered Trademark) PL-20 for colour and taste in order to maintain treatment blinding.
Control group
Placebo

Outcomes
Primary outcome [1] 289135 0
Rey’s Verbal Learning Test (RVLT)

The RVLT (Rey, 1958) is a test of verbal learning and memory that has a long history of use both in the assessment of clinical memory disturbances as well as cognitive decline associated with normal ageing (van der Elst, van Boxtel, van Breukelen, & Jolles, 2005). The RVLT consists of 15 monosyllabic words that are presented to participants in a fixed sequence at the rate of one word every two seconds. After the presentation of words participants are required to free-recall as many words as they can. The encoding-recall procedure is repeated five times. In the last trial a 20-minute interval is imposed before participants repeat as many words as they can recall from the original list. The maximum and total number of correctly repeated words are recorded, together with the number of words recalled in the delayed-recall condition (Rey, 1958).
Timepoint [1] 289135 0
Baseline, 90 days (3 months) and 180 days (6 months)
Primary outcome [2] 289136 0
The Prospective and Retrospective Memory Questionnaire (PRMQ)

The PRMQ (Crawford, Smith, Maylor, Della Sala, & Logie, 2003) was developed in order to provide a self-report measure of prospective and retrospective memory omissions in everyday life. The PRMQ consists of 16 items, with 8 items enquiring about prospective memory failures and 8 items enquiring about retrospective memory failures. Each item is scored on a 5-part Likert scale from 1 (never) to 5 (very often). The total score range for the PRMQ is from 16 – 80, with higher scores indicating greater number of prospective and retrospective memory ommissions. An example of a retrospective item is: “do you fail to recognise a place you have visited before?” An example of a prospective item is: “do you fail to mention or give something to a visitor that you were asked to pass on?”
Timepoint [2] 289136 0
Baseline, 90 days (3 months) and 180 days (6 months)
Primary outcome [3] 289137 0
Mini-Mental State Examination (MMSE)

The MMSE is brief test commonly used in assessment of cognitive impairment and dementia that takes approximately 5 to 10 minutes to complete. The test comprises of 11 questions used to measure orientation time and place, immediate recall, short term verbal memory, calculation, language and construct ability. A score out of 30 is calculated at the end of the test.
Timepoint [3] 289137 0
Baseline, 90 days (3 months) and 180 days (6 months)
Secondary outcome [1] 301902 0
Swinburne University Computerized Cognitive Ageing Battery (SUCCAB)

The SUCCAB is a computerized test battery of tasks designed to capture a range of cognitive functions that decline with age. In the current study two tasks from the SUCCAB test battery will be used: Contextual Memory and Spatial Working Memory.
Spatial Working Memory
In each trial participants are presented with a 4x4 white grid on a black background, with six grid positions containing white squares. Participants are given 3 seconds to remember where the white squares are located. The grid became blank and a series of four white squares were sequentially displayed in various grid positions for 2-seconds each. Participants responded with a yes/no response to indicate whether each square matched a position that was originally filled. In total, participants complete 14 trials, each of which are separated by a blank screen displayed for 2-seconds. Each trial was set such that two out of the four locations in the response series corresponded to the original grid locations, and two did not. The task requires participants to hold spatial information in working memory.
Contextual Memory
A series of 20 everyday images are presented at the top/bottom/left/right of the screen for 3-seconds each with no ISI. On completion of the series the same images are displayed again in randomized order in the centre of the screen for 2-seconds each with no ISI. Participants respond with a top/bottom/left/right button press to indicate the original location of each image. The task requires participants to recall the spatial context of the original presentation and was used as a measure of episodic memory.
Timepoint [1] 301902 0
Baseline, 90 days (3 months) and 180 days (6 months)
Secondary outcome [2] 301903 0
The Cognitive Demand Battery
The objective of these tasks is to assess the impact of treatment on continuous cognitive demand. The overall cognitive load in the session increases as participants complete these tests repeatedly for a period of approximately 30-minutes. These tasks assess the interaction between a given intervention and 'mental demand'. The Cognitive Demand Battery comprised of two computerised serial subtraction tasks (Serial Threes and Serial Sevens) the Bakan Rapid Visual Information Processing task (RVIP) and a paper-and-pencil measure of mental fatigue.
Serial threes subtraction task (2 min):

Participants will be required to count backwards in threes from a given number as quickly and as accurately as possible using the computer keyboard number keys to enter each response. A random starting number between 800 and 999 will be presented on the computer screen, which will then be cleared by the entry of the first response. The task will be scored for number of correct responses and number of errors.

Serial sevens subtraction task (2 min):

This will be identical to the serial threes task with the exception that it will involve serial subtraction of sevens.


Rapid Visual Information Processing task (RVIP – 5 min):

The participant will be required to monitor a continuous series of digits for targets of three consecutive odd or three consecutive even digits. The digits will be presented at the rate of 100 per minute and the participant will be required to responded to the detection of a target string by pressing the ‘space bar’ as quickly as possible. The task will be continuous and last for 5 minutes, with 8 correct target strings being presented in each minute. RVIP will be scored for percentage of target strings correctly detected, average reaction time for correct detections, and number of false alarms.
Timepoint [2] 301903 0
Baseline, 90 days (3 months) and 180 days (6 months)
Secondary outcome [3] 301904 0
Hick's Reaction Time paradigm (Jensen box task)

The Jensen box is an apparatus that distinguishes decision time and movement time from total reaction time. This apparatus has eight lights which are arranged in a semi-circular configuration. A response button is located adjacent to each light. A "home" button is situated in the centre of the panel. Subjects are required to press the home button until they see a target light and then to release the home button as quickly as possible and to press the response button adjacent to the stimulus light. Decision time (DT) is defined as the time from stimulus onset to the release of the home button, and movement time (MT) as the time from release of the home button to the depression of the stimulus button.

Choice is manipulated by varying the number of stimulus alternatives, from 0 (i.e. one light at one possible location) to multiple (i.e. the stimulus may appear in any one of the eight light positions). Participants will be given several practice trials in the eight stimulus (i.e. eight lights) condition so that they can familiarise themselves with the task. DTs of less than 150 ms are discarded as outliers, as it has been argued that physiological limits prevent shorter DTs (Jensen, 1987). DTs over 999 ms will also be discarded and replaced with an additional trial. In addition, all DTs exceeding three SDs above the subject's mean DT are also discarded (Jensen, 1987). The outcome measures are the median, mean and intra-individual variability (*i - average standard deviation) of both DT and MT for all choice, intercept of the DT function across choice and the slope of this function.
Timepoint [3] 301904 0
Baseline, 90 days (3 months) and 180 days (6 months)
Secondary outcome [4] 301905 0
Mood measures

Beck Depression Inventory (BDI-II)

The Beck Depression Inventory (BDI-II) is a 21-item; self-report inventory designed to measure the severity of depressive symptoms. The BDI-II is one of the most widely used depression inventories in both clinical and research settings. The BDI-II asks participants to rate how they have felt over the past 2 weeks on a scale of 0 (no symptoms) to 3 (severe symptoms). Higher scores on the BDI-II indicates more severe depressive symptoms. The BDI-II has adequate test-retest reliability and high internal consistency. Furthermore, the BDI has been shown to be effective in measuring depressive symptoms in older populations (Gallagher, Nies, & Thompson, 1982). In the current study a cut off of 20 and higher will be used as evidence of severe depression.

The Depression, Anxiety and Stress Scale (DASS)

This short questionnaire has three sub-factors: depression, anxiety and stress. The DASS is relevant for both clinical and non-clinical populations and has adequate reliability and validity. The 21 items comprise affect related symptoms, pertaining to possible dysfunction or disorder, on a 4-point scale from 0 to 3, thus yielding a possible range from 0 to 63. Higher scores indicate a higher degree of dysfunction and less desirable affect experience. A score of zero does not indicate positive mood, but rather the lack of presence of symptoms pertaining to dysphoric mood. Nevertheless the DASS is considered suitable for normal populations as some experience of such symptoms is considered normal in day-to-day life.

Profile of Mood States (POMS)

The POMS (McNair, Lorr, & Droppleman, 1992) is a self-report questionnaire designed to measure six dimensions of mood: tension-anxiety; depression-dejection; anger-hostility; vigour-activity; fatigue-inertia; and confusion-bewilderment. The POMS consists of 65 adjectives describing feeling and mood which is answered on a five-point Likert-type scale ranging from not at all to extremely. Respondents are asked to indicate mood reactions for the "past week including today".


Bond-Lader Visual Analogue Mood Scales
The Bond- Lader Visual Analogue Mood Scales (Bond & Lader, 1974) were originally designed for assessing the mood effects of anxiolytics and have been subsequently utilized in numerous pharmacological, psychopharmacological, and medical trials. As with other mood visual analogue scales, high reliability and validity have been demonstrated (Ahearn, 1997). The Bond and Lader scales comprise a total of 16 100-mm lines anchored at either end by antonyms. Participants mark their current subjective state between the antonyms on the line. Each line is scored as millimeters to the mark from the negative antonym. From the resultant scores, three measures derived by factor analysis can be isolated. These have been described by Bond and Lader as representing the following: "alertness" (represented by lines anchored by alert–drowsy, attentive–dreamy, lethargic–energetic, muzzy–clearheaded, well-coordinated–clumsy, mentally slow–quick witted, strong–feeble, interested–bored, incompetent–proficient); "calmness" (calm–excited, tense–relaxed); and "contentedness" (contented–discontented, troubled–tranquil, happy–sad, antagonistic–friendly, withdrawn–sociable). Scores for each factor represent the unweighted average number of millimeters (maximum 100 mm) from the negative antonym for the individual scales contributing to the factor.
Timepoint [4] 301905 0
Baseline, 90 days (3 months) and 180 days (6 months)
Secondary outcome [5] 301906 0
Cardiovascular measures

Cardiovascular measures will be assessed using standard blood pressure assessment, SphygmoCor applanation tonometry, Transcranial Doppler as well as Flow Mediated Dilation. The SphygmoCor is a non-invasive tool that measures aortic blood pressure and vascular elasticity (arterial stiffness). Transcranial Doppler, also a non-invasive device, will be used to measure blood velocity in both the Middle Cerebral and Common Carotid arteries. Flow Mediated Dilation will be used to assess endothelial dependent vasodilation of the brachial artery. Such cardiovascular equipment adheres to the necessary Australian safety standards and is commonly used to assess and manage cardiovascular health.

1. Blood pressure
Brachial blood pressure will be calculated with the participant seated and following a five minute rest period. Measurements will be calculated using a sphygmomanometer and an appropriately sized cuff. To ensure the accuracy of the assessment, blood pressure will be taken three times and averaged.

2. SphygmoCor
Aortic blood pressure, pulse pressure and pulse wave velocity (all aspects of arterial stiffness and cardiovascular pressures) will be measured non-invasively using the SphygmoCor. The researcher will place 3 recording electrode stickers on the participant’s chest in a lead II configuration. This will capture the participant’s heart rhythm. Using a pencil-like sensor, the researchers will record the participants pulse allowing the SphygmoCor device to automatically derive all parameters of interest.

3. Transcranial Doppler
This non-invasive system will be used to record Middle Cerebral Artery (MCA) blood velocity by placing a sensor close to the participant’s ear whilst Common Carotid Artery (CCA) blood velocity will be recorded by gently placing a hand held sensor at the base of the participant’s neck.

Timepoint [5] 301906 0
Baseline, 90 days (3 months) and 180 days (6 months)
Secondary outcome [6] 301907 0
Biochemical Assessments

Haematological testing will be conducted at training, baseline, 90 and 180 days. Blood samples will be used to measure HbA1c (glycated haemoglobin - an index of blood glucose levels over the previous few weeks). Glucose control is well documented to decrease with age (Fink et al 1983), and this effect is suggested to contribute to age-related cognitive decline (Messier et al 2003; Riby et al 2004). Therefore, we will measure glucoregulatory efficiency in our dataset of elderly individuals to ensure that differences in cognitive performance are not due to differences in glucoregulatory control.

On the other assessment days (i.e. baseline, 90 and 180 days) blood samples will be taken in order to measure biochemical markers of oxidative stress (glutathione and F2 isoprostanes) and inflammation (cytokines TNF-a, interleukins 1ß/6 and C-reactive protein) together with blood levels of B-Vitamins (B6,B9,B12) and homocysteine (HCy) levels.

Improved HCy levels have been found to result from increased intake of phosphatidylcholine and choline. For these reasons serum choline will also be monitored throughout the study.
Timepoint [6] 301907 0
Baseline, 90 days (3 months) and 180 days (6 months)
Secondary outcome [7] 301908 0
Pharmacogenetic measures

Blood samples obtained from haematological testing will also be used for the purpose of genetic assessment. Specifically, bloods will be analysed to determine the presence or absence of the APOE e4 allele as well as for polymorphisms in the MTHFR gene. Blood sampling for genetic analysis will be conducted once at the baseline study visit (V1).

APOE Genotyping

Genotyping for the APOE e4 allele will be used to investigate whether participants with and without the APOE e4 allele respond to the treatments differently and show differential relationships with the cognitive and biological variables.

The results of the APOE testing may indicate an individual is at a higher risk of developing late onset Alzheimer’s disease. However, it is not possible to determine whether an individual will eventually develop Alzheimer’s disease based on the presence of the APOE e4 allele.

The following steps will be taken to manage this information:
Information about the APOE testing will be included in the Form of Disclosure. Participants will also be provided with an Alzheimer’s Disease Genetic fact sheet (see attached) to read prior to signing the consent form. The researchers will not disclose the results of the APOE testing to the participants. Release of genetic data will be done in consultation with the participants GP.

In the situation that a participant requests access to their results, the release of genetic data will be done in consultation with the participants GP. The GP will be provided with the Alzheimer’s Disease Genetic fact sheet and some information regarding the APOE status test in relation to the research project to read prior to consultation with the participant. The GP will also be provided with the contact details of a qualified genetic counselor to refer participants to make an appointment to discuss their results if they experience any further concerns about the meaning of these results.

MTHFR Genotyping

The methyltetrahydrofolate reductase (MTHFR) gene has been found to influence the way in which B-Vitamins are metabolised, as well as the accumulation of Homocysteine. Genotyping for the MTHFR gene will be used to investigate whether polymorphisms in the MTHFR gene influence the effects of Lacprodan(Registered Trademark) PL-20 on cognition and mood. MTHFR status has not been found to be a risk factor for dementia, although it may indicate the extent to which homocysteine is accumulated in the body.
Timepoint [7] 301908 0
Baseline, 90 days (3 months) and 180 days (6 months)
Secondary outcome [8] 301909 0
Neuroimaging
In a subset of 40 participants neuroimaging with functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) will be conducted in order to further explore the in vivo mechanisms of action of Lacprodan(Registered Trademark) PL-20 in the brain. Previous neuroimaging studies using phosphatidylserine (PS) supplementation in AD have been conducted using electroencephalography (EEG) as well as positron emission tomography (PET). PET results revealed that for the PS group there was increased glucose metabolism during a visual recognition task across a number of brain regions, most notably the temperoparietal regions [120]. However, to-date no further neuroimaging studies have been conducted using phospholipid interventions, and to the best of our knowledge none have been conducted using MRI or MEG.
In the current study structural and functional MRI scans will be acquired using a Siemens 3 Telas tin trio MRI scanner, located at the Centre for Human Psychopharmacology, Swinburne University of Technology. During the initial scan, a structural image will be obtained for each participant and used as a reference point for further functional scans. Scanning for diffusion tensor imaging (DTI) analysis, a measure of white matter integrity, will also be conducted. Following DTI there will be scanning in a resting state in order to assess activity in the default mode network (DMN, approx. 6 minutes). Additional analysis of cell membrane fluidity will also be conducted by using the T2 signal timing information (relaxometry) while in a resting state. Changes in the blood oxygenation-level dependent (BOLD) signal will also be analysed while participants complete in-scanner versions of verbal episodic memory (approx. 20 minutes) and N-Back working memory tasks (approx. 20 mintues).
MEG scanning will be conducted using an Elekta Neuromag TRIUX MEG system, also located at the Centre for Human Psychopharmacology, Swinburne University of Technology. Initial scanning while in a resting state will be conducted in order to collect information as to activity in the default mode network (DMN). Following this scanning will be conducted whilst participants complete the same in-scanner tasks as used in the fMRI task: verbal episodic memory and N-Back working memory. The two tasks are kept the same across both fMRI and MEG in order for information from the two imaging modalities to be combined into a single comprehensive analysis. MEG scanning provides important complementary information which is additional to that provided by fMRI. The temporal resolution of MEG is far superior to fMRI; MEG is capable of recording neural oscillations from delta right through to the gamma range (>40Hz). Whilst the spatial resolution of MEG is less than that of fMRI, the high number of sensors (approx. 300) together with modern source reconstruction algorithms (e.g. beam forming) means that the spatial resolution of MEG is far superior to conventional scalp-recorded EEG. The combination of the two imaging modalities is state-of-the-art and will provide an unparalleled level of analysis regarding the effects of Lacprodan(Registered Trademark) PL-20 on memory function.
Timepoint [8] 301909 0
Baseline, 90 days (3months) and 180 days (6 months)

Eligibility
Key inclusion criteria
-Male or female.

-Aged >55 years.

-Meets diagnostic criteria for age-associated memory impairment: AAMI is defined on the basis of criteria first outlined by Crook et al: (i) A score >25 on the Memory Complaint Questionnaire (MAC-Q) and (ii) a score at =1 standard deviation below the mean for healthy young adults on the Paired Associates Test from the Wechsler Memory Scale - Revised (WMS-R)

-Willing and able to provide written informed consent.

-Understands and is willing and able to comply with all study procedures.

-English speaking.

-Normal or corrected vision.

-Must be right-handed (applies only to the neuroimaging sub-study).
Minimum age
56 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Dementia and/or MMSE score <24.
Neurological, cardiac, endocrine, gastrointestinal or bleeding disorders.
Psychiatric illness including mood disturbance/depression, as confirmed with a BDI-II >=20.
History of alcoholism and/or substance abuse.
Any known or suspected allergy to cow’s milk and/or lactose intolerance.
Smoker.
Participation in another clinical trial during the past 2 months.
Using any medications that could affect the outcome of the study including any pharmacological agents with known cognitive effects and diabetic medications.
Taking vitamins or herbal supplements regularly.

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)
Randomisation of participants to treatment groups will be determined by random allocation. Eligible, recruited participants will be assigned a participant number. The participant will receive the treatment that has been randomly allocated to that participant number. For the neuro-imaging sub-study sixty randomisation numbers will be set aside which correspond to 10 lacprodan, 10 rice starch placebo, 10 milk protein placebo for females and 10 lacprodan, 10 rice starch placebo, 10 milk protein placebo for males. The first 30 males and 30 females who have indicated their willingness to participate in the neuro-imaging component of the study will be assigned one of these sub-study specific randomisation numbers. Allocation concealment will be achieved by means of a label identification code attached to the treatment containers. The identification code will be recorded in a treatment dispensing log (maintained by the study investigator) and cross-referenced to the participant number to whom the treatment was dispensed. Blinding for both the main study as well as the neuro-imaging sub-study will be achieved by enlisting a Centre for Human Psychopharmacology staff member who is outside of the project to code the treatments, and maintain the key to this code until data collection is completed. Two copies of the randomisation codes will be kept throughout the trial; one for administration purposes (A,B,C) and one for emergency code break situations (unblinding). Whilst the investigation is a double blind trial, investigators will know the whereabouts of, and have access to, this information. The unblinded code list will only be broken in an emergency, such as an SAE that requires knowledge of the treatment being taken in order to manage a participant’s condition. The principle investigator and ethics committee will be informed within 24 hours of the code-break envelope being opened. Once testing has been completed, the randomisation schedule (A,B,C) will be revealed to the investigators in order to compile data sets for analysis. Unblinding will subsequently be conducted once final data analysis has been completed and it is time for generating the final report and publishing the research findings.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomization will be achieved by computerized sequence generation.
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
The three groups will be stratified according to age, IQ as measured by Raven’s Progressive Matrices (RPM), and baseline cognitive ability as measured by the WMS-R Paired Associates test
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The primary analysis will investigate the effect of treatment on all cognitive outcomes from baseline to 180 days, using the groups as randomised (“intension to treat”). Statistical analyses will be conducted using Linear Mixed modelling, whereby subject-specific random intercepts and slopes will be fitted to subject data and fixed effects will be fitted to treatment group, time and the treatment x time interaction. On the basis of APOE and MTHFR genotyping, subgroup analysis will also be conducted in order to investigate the effect of allelic differences on treatment response. Secondary outcome variables will be analysed using similar statistical techniques. Results will be considered statistically significant at p< 0.05 corrected for multiple comparisons. While stratification according to age, intelligence and baseline WMS-R scores may help to explain some of the residual between-group variance unrelated to the treatment effect, further exploration of possible covariates will also be investigated. Baseline correlations between the primary cognitive outcome measures and other baseline variables including body mass index, educational background, diet, cardiovascular function and biochemical parameters will also be investigated in order to investigate other important covariates. In the event that significant correlations at the p<.05 level are found at baseline then these additional variables will also be controlled for in the primary analysis of cognitive outcomes. Analysis of functional neuro imaging data (both MEG and fMRI) during episodic memory and N-Back working memory tasks will be conducted using a region of interest (ROI) approach. Using this method, between-group (Lacprodan(Registered Trademark) PL-20 versus rice starch placebo and Lacprodan(Registered Trademark) PL-20 versus milk protein placebo) functional differences in predefined brain regions will be statistically analysed. The ROIs for the episodic memory task will include the medial temporal lobes, the lateral prefrontal cortices, the associative temporal and paretial regions, the cingulate gyrus and the cerebellum. The ROIs that will be analysed in the N-Back working memory task will include the dorsolateral, ventrolateral and medial prefrontal cortex, anterior cingulate, parietal cortex and sensorimotor cortex. The required sample size for this study is 150 participants, with 50 participants assigned to each treatment group (Lacprodan(Registered Trademark) PL-20, rice starch placebo and milk protein placebo). Allowing for a 20% drop-out rate over the course of the 180-day testing period, this will give 80% power to detect significant treatment x time interactions from baseline to 180 days for primary cognitive outcomes of small-medium effect size (f=0.14). (Calculated using G*Power 3.1, with a=0.05 and r=0.5 for the correlation between repeated measures).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/09/2013
Actual
12/08/2014
Date of last participant enrolment
Anticipated
1/12/2015
Actual
9/03/2017
Date of last data collection
Anticipated
Actual
11/10/2017
Sample size
Target
150
Accrual to date
Final
138
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 6597 0
3122 - Hawthorn

Funding & Sponsors
Funding source category [1] 286933 0
Commercial sector/Industry
Name [1] 286933 0
Arla Foods Ingredients
Country [1] 286933 0
Denmark
Primary sponsor type
University
Name
Swinburne University of Technology
Address
Advanced Technologies Centre
427-451 Burwood Rd
Hawthorn
Victoria
3122
Country
Australia
Secondary sponsor category [1] 285722 0
None
Name [1] 285722 0
Address [1] 285722 0
Country [1] 285722 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288989 0
Swinburne University Human Research Ethics Committee
Ethics committee address [1] 288989 0
Ethics committee country [1] 288989 0
Australia
Date submitted for ethics approval [1] 288989 0
14/12/2012
Approval date [1] 288989 0
03/04/2014
Ethics approval number [1] 288989 0
2012/294

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

Contacts
Principal investigator
Name 38682 0
Prof Andrew Scholey
Address 38682 0
Level 10, Room 10.40
Advanced Technologies Centre (ATC)
Swinburne University of Technology
427-451 Burwood Rd
Hawthorn, Victoria
3122
Country 38682 0
Australia
Phone 38682 0
+613 9214 8932
Fax 38682 0
Email 38682 0
[email protected]
Contact person for public queries
Name 38683 0
Antionette Goh
Address 38683 0
Level 10, Room 10.09
Advanced Technologies Centre (ATC)
Swinburne University of Technology
427-451 Burwood Rd
Hawthorn, Victoria
3122
Country 38683 0
Australia
Phone 38683 0
+613 9214 5094
Fax 38683 0
Email 38683 0
[email protected]
Contact person for scientific queries
Name 38684 0
Andrew Scholey
Address 38684 0
Level 10, Room 10.40
Advanced Technologies Centre (ATC)
Swinburne University of Technology
427-451 Burwood Rd
Hawthorn, Victoria
3122
Country 38684 0
Australia
Phone 38684 0
+613 9214 8932
Fax 38684 0
Email 38684 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
Participants will be provided with their individual data upon request. In all publications, conferences, reports etc. only de-identified aggregate data will be presented. As this trial is industry-sponsored and there may be issues of intellectual property, raw data will not be made available unless the publishing journal requests it. In this case, with the sponsor's permission data will be made available in an appropriate repository.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
2979Study protocolScholey et al. (2013). A randomized controlled trial investigating the neurocognitive effects of Lacprodan® PL-20, a phospholipid-rich milk protein concentrate, in elderly participants with age-associated memory impairment: the Phospholipid Intervention for Cognitive Ageing Reversal (PLICAR): study protocol for a randomized controlled trial, BMC Trials, 14:404, DOI: https://doi.org/10.1186/1745-6215-14-404  
2980OtherReddan et al. (2018). Glycerophospholipid Supplementation as a Potential Intervention for Supporting Cerebral Structure in Older Adults, Frontiers in Aging Neuroscience, 10:49. DOI: 10.3389/fnagi.2018.00049.   Literature review relating to the investigational ... [More Details]



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SourceTitleYear of PublicationDOI
EmbaseDiet May Moderate the Relationship between Arterial Stiffness and Cognitive Performance in Older Adults.2022https://dx.doi.org/10.3233/JAD-210567
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