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Trial registered on ANZCTR


Registration number
ACTRN12619000112167
Ethics application status
Approved
Date submitted
10/01/2019
Date registered
24/01/2019
Date last updated
7/05/2019
Date data sharing statement initially provided
24/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Blackmores Memory (ARCLI II): Investigating the safety and efficacy of a Blackmores micronutrient formula on cognitive function in healthy adults aged 50-75 years.
Scientific title
Investigating the safety and efficacy of acute and chronic administration of Blackmores’ ARCLI proprietary formula on cognitive function and mood in healthy adults
Secondary ID [1] 296712 0
None
Universal Trial Number (UTN)
Trial acronym
ARCLI-II
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cognitive function 310563 0
Mood 310564 0
Cardiovascular function 310565 0
Brain function 310566 0
Condition category
Condition code
Mental Health 309276 309276 0 0
Studies of normal psychology, cognitive function and behaviour
Cardiovascular 309277 309277 0 0
Normal development and function of the cardiovascular system
Neurological 309278 309278 0 0
Studies of the normal brain and nervous system
Alternative and Complementary Medicine 309279 309279 0 0
Other alternative and complementary medicine

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Blackmores' Micronutrient formulation:

The excipient ingredients of the active formulation have been kept private at the request of the sponsor.

The micronutrient formulation contains 12.5mg Pyridoxine Hydrochloride, 200mcg Folic Acid, 150mg r, s-alpha lipoic acid, 250mcg Cyanocobalamin, and 41.6mg Soy Lecithin (equivalent to 25mg Phosphatyldiserine.

Participants will be asked to consume 1 capsule, twice daily with food (Total of 2 capsules per day, one in the morning and one in the evening), for 90 days in their own home. Participants will also be supplied with an additional 14 days' supply of capsules in case the final visit is delayed.

Participants will be provided with a diary/log that they will be instructed to tick when they have taken their treatment each day. In addition, they will be required to return any left over treatment at their final visit so that compliance can be calculated based on capsule count.

A sub-group of 40 participants will undergo MRI assessment to investigate changes in brain function. Randomisation will be stratified such that 20 participants per treatment arm will undergo this procedure. Participants will be allocated to this sub-group based on their interest in taking part in the additional procedures and additional inclusion/exclusion criteria such as having no metal implants.
Intervention code [1] 313021 0
Treatment: Drugs
Comparator / control treatment
The placebo treatment contains Silica-Colloidal Anhydrous (6mg), Cellulose-Microcystalline (240mg), Magnesium Stearate (10mg), iron oxide red (0.19mg) and iron oxide yellow (0.45mg) in an opaque white, 2-piece hard capsule, made of hydroxypropyl methyl cellulose (gelatine free) and titanium dioxide.

The placebo capsules are identical in appearance to those containing the active treatment. Participants will be asked to consume 1 capsule, twice daily with food (Total of 2 capsules per day, one in the morning and one in the evening), for 90 days in their own home.
Control group
Placebo

Outcomes
Primary outcome [1] 308254 0
Memory composite score, calculated from the memory tasks included in the CogTrack cognitive testing battery.
Timepoint [1] 308254 0
3 months post first dose
Secondary outcome [1] 354397 0
Non-memory cognitive function composite score, calculated from the simple reaction time, choice reaction time and digit vigilance tasks in the CogTrack cognitive testing battery.
Timepoint [1] 354397 0
3 months post first dose.
Secondary outcome [2] 354398 0
Subjective memory assessed using the Prospective and Retrospective Memory Questionnaire (PRMQ)
Timepoint [2] 354398 0
3 months post first dose
Secondary outcome [3] 354399 0
Mood assessed using the Profile of Mood States (POMS)
Timepoint [3] 354399 0
3 months post first dose
Secondary outcome [4] 354400 0
Cardiovascular function measured using SphygmoCor
Timepoint [4] 354400 0
3 months post first dose
Secondary outcome [5] 354401 0
Oxidative stress measured as levels of F2 isoprostanes in blood.
Timepoint [5] 354401 0
3 months post first dose
Secondary outcome [6] 354402 0
Safety measured using participants' self-reported adverse event reports, measures of kidney and liver function (urea, electrolytes, total bilirubin, total protein, albumin, globulin, alkaline phosphatase, alanine aminotransferase. gamma glutamyl transferase) assessed in blood, and a symptoms checklist questionnaire developed by Swinburne University's Brain Sciences Institute to assess the side effects of natural medicines. Possible side effects of this supplement include: diarrhoea, abdominal pain, nausea, vomiting, bloating, trouble sleeping, headache, skin tingling, sleepiness, and skin redness.
Timepoint [6] 354402 0
Monitored throughout study.
Secondary outcome [7] 354403 0
Brain function measured using Magnetic Resonance Spectroscopy (MRS; conducted in MRI sub-group of 40 participants only)
Timepoint [7] 354403 0
3 months post first dose
Secondary outcome [8] 354404 0
Resting state functional connectivity in the brain measured using a resting state sequence in MRI (conducted in MRI sub-group of 40 participants only).
Timepoint [8] 354404 0
3 months post first dose
Secondary outcome [9] 354405 0
Cognitive performance of the n-back task whilst undergoing brain imaging procedures ((conducted in MRI sub-group of 40 participants only).
Timepoint [9] 354405 0
3 months post first dose.
Secondary outcome [10] 354406 0
Memory composite score, calculated from the memory tasks included in the CogTrack cognitive testing battery.
Timepoint [10] 354406 0
14 days post first dose
Secondary outcome [11] 354407 0
Memory composite score, calculated from the memory tasks included in the CogTrack cognitive testing battery.
Timepoint [11] 354407 0
30 days post first dose
Secondary outcome [12] 354408 0
Memory composite score, calculated from the memory tasks included in the CogTrack cognitive testing battery.
Timepoint [12] 354408 0
60 days post first dose
Secondary outcome [13] 354409 0
Non-memory cognitive function composite score, calculated from the simple reaction time, choice reaction time and digit vigilance tasks in the CogTrack cognitive testing battery.
Timepoint [13] 354409 0
14 days post first dose
Secondary outcome [14] 354410 0
Non-memory cognitive function composite score, calculated from the simple reaction time, choice reaction time and digit vigilance tasks in the CogTrack cognitive testing battery.
Timepoint [14] 354410 0
30 days post first dose
Secondary outcome [15] 354411 0
Non-memory cognitive function composite score, calculated from the simple reaction time, choice reaction time and digit vigilance tasks in the CogTrack cognitive testing battery.
Timepoint [15] 354411 0
60 days post first dose
Secondary outcome [16] 354412 0
Subjective memory assessed using the Prospective and Retrospective Memory Questionnaire (PRMQ)
Timepoint [16] 354412 0
14 days post first dose
Secondary outcome [17] 354413 0
Subjective memory assessed using the Prospective and Retrospective Memory Questionnaire (PRMQ)
Timepoint [17] 354413 0
30 days post first dose
Secondary outcome [18] 354414 0
Subjective memory assessed using the Prospective and Retrospective Memory Questionnaire (PRMQ)
Timepoint [18] 354414 0
60 days post first dose
Secondary outcome [19] 354415 0
Mood assessed using the Profile of Mood States (POMS)
Timepoint [19] 354415 0
14 days post first dose
Secondary outcome [20] 354416 0
Mood assessed using the Profile of Mood States (POMS)
Timepoint [20] 354416 0
30 days post first dose
Secondary outcome [21] 354417 0
Mood assessed using the Profile of Mood States (POMS)
Timepoint [21] 354417 0
60 days post first dose

Eligibility
Key inclusion criteria
People who meet the following inclusion criteria will be included in the trial:
1. Male or female, aged 50-75 years, inclusive.
2. Willing and able to provide written informed consent.
3. Understands and is willing and able to comply with all study procedures.
4. Fluent in written and spoken English.
5. Participants must be in general good health defined for the purposes of this study by the absence of the exclusion criteria and as judged by the Investigator/Clinical advisor on the basis of medical history.
6. Normal, or corrected to normal vision.
7. Participant has internet access in the home and has basic computer skills in order to complete the questionnaires and tasks online.
8. Willing to maintain habitual diet (including caffeine and alcohol) and physical activity patterns throughout the study period.
9. Willing to abstain from caffeine for 10 hours prior to and throughout the test visits, (up to 6 hours).
10. Willing to abstain from alcohol for 24 hours and vigorous physical activity for 12 hours prior to all study visits.
Minimum age
50 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
People who meet the following exclusion criteria will not be included in the trial:
1. Current smoker
2. History of Type I diabetes (insulin dependent) or Type II diabetes on treatment. (Type II diabetes and prediabetes treated with diet alone is not an exclusion).
3. Cardiovascular disease.
4. Neurological conditions including epilepsy, Parkinson’s disease, Myaesthenia Gravis, Huntington’s Chorea.
5. History of dementia, stroke or other neurological conditions.
6. Head trauma with loss of consciousness in the previous 6 months.
7. History of anxiety, depression, or psychiatric disorders requiring treatment in the last 2 years.
8. Current endocrine, gastrointestinal or bleeding disorders.
9. Current moderate or severe alcohol misuse disorder as defined in DSM5.
10. Current substance misuse disorder as defined in DSM5 (including misuse of prescription drugs)
11. Uncontrolled hypertension (systolic blood pressure >160 mm Hg or diastolic blood pressure > 100 mm Hg)
12. If female, pregnant or lactating.
13. Not willing to abstain from using vitamin E, multivitamins, B vitamin complex, ginkgo biloba, fish oil, St John’s Wort, or other cognitive enhancing dietary or herbal supplements over the study period.
14. Taking the following (in the 4 weeks preceding the baseline visit and for study duration):
i. Vitamin supplements including multivitamins, B vitamin complex, vitamin E
ii. Herbal supplements including ginkgo biloba, fish oil, St John’s Wort or other cognitive enhancing dietary or herbal supplement.
iii. Anti-coagulant drugs (warfarin, heparin, clopidogrel, aspirin, dipyrimidole, apixiban , rivaroxiban, dabigatran, tirofiban , ticagrelor);
iv. anti-cholinergics or acetylcholinesterase inhibitors (bethanechol (Urecholine), donepezil (Aricept), rivastigmine (Exelon), galantamine (Reminyl), pyridostigmine (Mestinon)
v. anti-depressant medications
vi. anti-anxiety medication including benzodiazepines
vii. Hypnotics including benzodiazepines, zolpidem and zopiclone
15. Allergy to the investigational product or any of the ingredients.
16. Participation in any other study involving an investigational product in the preceding 4 weeks.
For imaging participants ONLY:
17. Left-handed.
18. Metal implants such as metal joints, pacemakers, or stents.
19. Claustrophobic

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)
Allocation will be concealed by sealed opaque envelopes, which are to be kept in a locked filing cabinet in the Principal Investigator's office and will only be opened in the case of an emergency. In addition, the full randomisation list will be kept in a password protected document in a restricted access confidential folder on a secure server. Only the Laboratory Manager (who is responsible for generating the randomisation list) and the Clinical Trials Coordinator will have the password to access this document.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation for this trial will be conducted using computerised sequence generation, and stratification based on MRI status (included in MRI subgroup or not) will be used.
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
Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
For each outcome measure, data will be manually screened and (only) data deemed ‘invalid’ will be omitted from analyses. Data will be deemed invalid if a biological rationale sustains this assumption, e.g. non-physiological values or in the case of cognitive and psychological variables, data that violates the task requirements and could be considered as outliers as deemed by standard statistical processes. These invalid data and the reason for exclusion will be reported in the final report. Demographic data will be presented with summary statistics (number of participants, mean, standard deviation, median and range). The number and percentage of subjects will be presented for categorical variables.
Repeated measures ANOVAs (Time by Treatment effects) will be used to analyse the primary and secondary parameters. Analysis of variance using the SPSS Version 23 statistical package will be conducted to ascertain any significant group differences reflecting effects of the treatment over time for the two groups on the cognitive, subjective memory and mood measures. Demographic data will be analysed using univariate analyses of variances (ANOVAs) in SPSS, applying standard statistical thresholds (p < 0.05), corrected for multiple comparisons where appropriate with two tailed significance level. Individual means will be obtained for each outcome measure and group means, collapsed across the two treatment arms, will be calculated to determine treatment effects. Relationships between memory, subjective memory and mood will also be performed using Pearson’s correlation coefficient or the non-parametric equivalent, Spearman’s R.

Recruitment
Recruitment status
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)
VIC

Funding & Sponsors
Funding source category [1] 301292 0
Commercial sector/Industry
Name [1] 301292 0
Blackmores Ltd
Address [1] 301292 0
20 Jubilee Avenue
Warriewood
NSW 2102
Country [1] 301292 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Blackmores Ltd
Address
20 Jubilee Avenue
Warriewood
NSW 2102
Country
Australia
Secondary sponsor category [1] 300945 0
None
Name [1] 300945 0
Address [1] 300945 0
Country [1] 300945 0
Other collaborator category [1] 280445 0
University
Name [1] 280445 0
Swinburne University of Technology
Address [1] 280445 0
PO Box 218
Hawthorn
VIC 3122
Country [1] 280445 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302033 0
Swinburne University Human Research Ethics Committee
Ethics committee address [1] 302033 0
Research Ethics, Integrity and Biosafety Office
Swinburne Research (H68)
PO Box 218
Hawthorn VIC 3122
Ethics committee country [1] 302033 0
Australia
Date submitted for ethics approval [1] 302033 0
27/09/2018
Approval date [1] 302033 0
30/11/2018
Ethics approval number [1] 302033 0
SHR Project 2018/363

Summary
Brief summary
The current study will sample healthy older volunteers aged 50-75 years to examine the effects of the Blackmores micronutrient formulation on cognitive function, mood, cardiovascular function and brain function. Research has investigated the individual components of the combination formula but research is yet to examine the effects of this newly devised combination formula on cognitive, cardiovascular and biochemical outcomes.

One hundred and twenty participants will be recruited to take part in this trial, to allow for a complete set of 100 participants after attrition. Participants will complete three visits at the site (screening, baseline and 90 days follow-up), as well as three testing sessions completed online in their own home (14 days, 30 days and 60 days post first dose). Forty participants (20 per treatment arm) will also undergo brain imaging procedures at the baseline and follow-up visits.

We hypothesize that significant improvement in cognition will occur after 3 months administration of the combination formula relative to placebo. In addition, it is hypothesized that the largest cognitive improvements will be seen at the longest time points (3 months) of administration. Secondary or exploratory outcomes/hypotheses concern the effect of this supplement on the neuroimaging, biochemical and neuropsychological variables.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 88910 0
Prof Con Stough
Address 88910 0
Swinburne University of Technology
Centre for Human Psychopharmacology
ATC Building, Mail H24
John Street,
Hawthorn
Victoria 3122
Country 88910 0
Australia
Phone 88910 0
+61 3 9214 8167
Fax 88910 0
Email 88910 0
cstough@gmail.com
Contact person for public queries
Name 88911 0
Dr Naomi Perry
Address 88911 0
Swinburne University of Technology
Centre for Human Psychopharmacology
ATC Building, Mail H24
John Street,
Hawthorn
Victoria 3122
Country 88911 0
Australia
Phone 88911 0
+61 3 9214 8930
Fax 88911 0
Email 88911 0
nlperry@swin.edu.au
Contact person for scientific queries
Name 88912 0
Prof Con Stough
Address 88912 0
Swinburne University of Technology
Centre for Human Psychopharmacology
ATC Building, Mail H24
John Street,
Hawthorn
Victoria 3122
Country 88912 0
Australia
Phone 88912 0
+61 3 9214 8167
Fax 88912 0
Email 88912 0
cstough@gmail.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
It is expected that the results of this trial will be disseminated via peer-reviewed publications and at academic conferences. For these purposes the data will be collated and analysed as group data. If required by the publishing journal, de-identified raw data will be uploaded to an appropriate repository. Otherwise, as the Intellectual Property of this study are owned by the sponsor and may be used for the purposes of commercialisation of the study product, the trial data will not be made available.
What supporting documents are/will be available?
No other documents available
Summary results
No Results