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Trial registered on ANZCTR


Registration number
ACTRN12611000487910
Ethics application status
Approved
Date submitted
20/04/2011
Date registered
10/05/2011
Date last updated
21/11/2018
Date data sharing statement initially provided
21/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The chronic effects of Bacopa and Pycnogenol on cognitive and cardiovascular function in a healthy older population
Scientific title
The chronic effects of Bacopa and Pycnogenol on cognitive and cardiovascular function in a healthy older population
Secondary ID [1] 253063 0
None
Universal Trial Number (UTN)
Trial acronym
ARC-LI
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Effects of natural supplements on cognition 258626 0
Effects of natural supplements on mood 258627 0
Effects of natural supplements on cardiovascular function 258628 0
Effects of natural supplements on inflammation and oxidative stress 258629 0
Mechanisms of natural supplements 258630 0
Effects of natural supplements on brain function 310525 0
Effects of natural supplements on gut microbiota 310526 0
Condition category
Condition code
Alternative and Complementary Medicine 258770 258770 0 0
Herbal remedies
Mental Health 265976 265976 0 0
Studies of normal psychology, cognitive function and behaviour
Cardiovascular 265977 265977 0 0
Normal development and function of the cardiovascular system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will consume a nutraceutical treatment daily for 12 months. Participants will be randomly allocated to one of three natural supplements (each of which is taken as oral capsules): Bacopa Monniera (300mg/day), Pycnogenol (150mg/day), and a placebo.

In addition, a sub-group of 150 participants will be recruited and will complete baseline assessments only but will not receive any intervention. The data collected from these participants will be used to further explore the relationship between gut microbiota and cognitive function, and will form the basis of a PhD student's thesis.
Intervention code [1] 257585 0
Other interventions
Intervention code [2] 264557 0
Prevention
Comparator / control treatment
Placebo (consisting of avicel, an inert plant cellulose fiber)
Control group
Placebo

Outcomes
Primary outcome [1] 259632 0
Speed of information processing via inspection
time on the Inspection Time Task and reaction time performance on the Hick Reaction Time Paradigm
Timepoint [1] 259632 0
at baseline, 3-month post-treatment commencement, 6-month post-treatment commencement and 12-month post-treatment commencement
Primary outcome [2] 259633 0
Memory via performance on the following computerised tasks: Immediate and delayed word recall, delayed word recognition, immediate and delayed picture recognition, contextual memory, spatial working memory, numeric working memory
Timepoint [2] 259633 0
at baseline, 3-month post-treatment commencement, 6-month post-treatment commencement and 12-month post-treatment commencement
Primary outcome [3] 259634 0
Sustained attention via the Rapid Visual Information Processing task
Timepoint [3] 259634 0
at baseline, 3-month post-treatment commencement, 6-month post-treatment commencement and 12-month post-treatment commencement
Secondary outcome [1] 266430 0
Subjective mood and anxiety via Bond and Lader Visual Analogue Scales, the Spielberger State-Trait Anxiety Inventory and Beck Depression Inventory II
Timepoint [1] 266430 0
at baseline, 3-month post-treatment commencement, 6-month post-treatment commencement and 12-month post-treatment commencement
Secondary outcome [2] 266432 0
Subjective fatigue and health via Short Form 36, Chalder Fatigue Scale and Leeds Sleep Evaluation questionnaire
Timepoint [2] 266432 0
at baseline, 3-month post-treatment commencement, 6-month post-treatment commencement and 12-month post-treatment commencement
Secondary outcome [3] 266433 0
Cardiovascular/arterial stiffness assessment via SphygmoCor system
Timepoint [3] 266433 0
at baseline, 3-month post-treatment commencement, 6-month post-treatment commencement and 12-month post-treatment commencement
Secondary outcome [4] 266434 0
Brachial blood pressure via automatic sphygmomanometer
Timepoint [4] 266434 0
at baseline, 3-month post-treatment commencement, 6-month post-treatment commencement and 12-month post-treatment commencement
Secondary outcome [5] 266435 0
Inflammation and oxidative stress via blood
samples. The haematological measures will include C-Reactive protein, F2 Isoprostanes, cytokines (TNF-alpha, Interleukin-1Beta, Interleukin 1-6 and Interleukin 10) and plasma Glutathione (GSH) concentration.
Timepoint [5] 266435 0
at baseline, 3-month post-treatment commencement, 6-month post-treatment commencement and 12-month post-treatment commencement
Secondary outcome [6] 276251 0
Middle cerebral artery blood velocity via Transcranial Doppler.
Timepoint [6] 276251 0
at baseline, 3-month post-treatment commencement, 6-month post-treatment commencement and 12-month post-treatment commencement
Secondary outcome [7] 276252 0
Flow mediated dilation of the brachial artery via ultrasound
Timepoint [7] 276252 0
at baseline, 3-month post-treatment commencement, 6-month post-treatment commencement and 12-month post-treatment commencement
Secondary outcome [8] 276253 0
Measurement of blood glucose using HbA1c (glycated haemoglobin) and Insulin.
Timepoint [8] 276253 0
at baseline, 3-month post-treatment commencement, 6-month post-treatment commencement and 12-month post-treatment commencement
Secondary outcome [9] 276254 0
Single Nucleotide Polymorphism (SNP) Genotyping from blood samples, using an array of candidate genes related to dementia, oxidative stress, antioxidant defence, individual variability in cognition, intelligence and behaviour and cardiovascular function.
Timepoint [9] 276254 0
Baseline
Secondary outcome [10] 276255 0
Telomere Length (a measure of DNA damage and biological aging) from blood samples
Timepoint [10] 276255 0
Baseline and 12-month post-treatment commencement.
Secondary outcome [11] 354235 0
Changes in the brain's structure, metabolites and blood flow following intervention, measured using magnetic resonance imaging (MRI).
Timepoint [11] 354235 0
Baseline, 3 months post first dose and 12 months post first dose
Secondary outcome [12] 354236 0
Gastrointestinal microbiota composition, measured using deep next-generation shotgun sequencing of DNA extracted from faecal samples.
Timepoint [12] 354236 0
At baseline, 3 months post first dose and 12 months post first dose.
Secondary outcome [13] 354237 0
Changes in the brain's structure, metabolites and blood flow following intervention, measured using magnetic resonance spectroscopy (MRS)
Timepoint [13] 354237 0
Baseline, 3 months post first dose and 12 months post first dose.
Secondary outcome [14] 354238 0
Changes in the brain's structure, metabolites and blood flow following intervention, measured using arterial spin labelled perfusion (ASL)
Timepoint [14] 354238 0
Baseline, 3 months post first dose and 12 months post first dose
Secondary outcome [15] 354239 0
Changes in the brain's structure, metabolites and blood flow following intervention, measured using default mode network scan (DMN)
Timepoint [15] 354239 0
Baseline, 3 months post first dose and 12 months post first dose.

Eligibility
Key inclusion criteria
Participants who meet the following inclusion criteria will be included in the trial;
1.) Healthy non-smoking males and females aged 60 - 75 years
2.) Free from psychiatric disorders
3.) No neurological diseases
4.) Not suffering from severe cardiovascular, gastrointestinal or endocrine disorders
5.) Not suffering from any other disorders affecting food metabolism
6.) No recent history (past 5 years) of chronic/severe illness (longer than 6 weeks)
7.) Must not be taking antidepressants, antipsychotics, anxiolytics, AChE inhibitors, illicit drugs or significant cognitive enhancing drugs that will interfere with the study measures (e.g. chronic intake of substances such as Ginkgo)
8.) Must score 24 and above on the Mini-Mental Status Examination (MMSE)
9.) Must score <20 on the Geriatric Depression Scale
10.) Must have corrected to normal vision
11.) No alcohol abuse (defined as greater than 14 standard drinks per week for women and 28 standard drinks per week for men) or addiction.
12.) No concurrent participation in any other clinical trial
For a sub-set of participants who will complete the MRS imaging, participants must also meet the following criteria in addition to the criteria above:
13.) Right handed
14.) Must not have any metal on or in your body such as that from any surgery involving metal plates and pace makers which increases the risk of having a Magnetic Resonance Imaging scan
15) Must not have non-removable body piercings
16) Must not have worked as a welder or have metal splinters in your body
Minimum age
60 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Participants who report any of the following will be excluded from the trial;
1.) Smokers
2.) Psychiatric disorder
3.) Neurological disease
4.) Significant endocrine, gastrointestinal or cardiovascular disorder
5.) Other disorders effecting food metabolism
6.) Recent history (past 5 years) of chronic/severe illness (longer than 6 weeks)
7.) Taking psychoactive medication including, antidepressants, antipsychotics, anxiolytics, AChE inhibitors, illicit drugs or significant cognitive enhancing drugs (e.g. chronic intake of substances such as Ginkgo)
8.) A score <24 on the MMSE
9.) A score >19 on the Geriatric Depression Scale
10.) Vision that is not corrected to normal
11.) Current regular alcohol use exceeding 14 standard drinks per week for women and 28 standard drinks per week for men
12.) Clinical trial participation additional to ARCLI

MRI Component
Participants who report any of the following will be excluded from the trial:
1.) Left handed
2.) Pacemaker
3.) Infusion pumps
4.) Aneurysm clips
5.) Metal protheses
6.) Metal joints
7.) Metal rods
8.) Metal plates
9.) Metal staples
10.) Non-removable body piercings
11.) Persons who have worked as welders or may have metal splinters in their body

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 treatment will be randomly assigned to the
subject by randomisation done by a third party, created off-site. Staff who enroll a subject into the study will provide a treatment bottle to the subject, which will already be numbered off-site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation by using a randomization table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis

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] 258129 0
Government body
Name [1] 258129 0
Australian Research Council
Address [1] 258129 0
Level 2, 11 Lancaster Place
Majura Park ACT 2609
Country [1] 258129 0
Australia
Funding source category [2] 258130 0
Commercial sector/Industry
Name [2] 258130 0
Flordis PTY LTD
Address [2] 258130 0
Lvl 5 156 Pacific Highway
St Leonards
New South Wales
2065
Country [2] 258130 0
Australia
Funding source category [3] 258131 0
Commercial sector/Industry
Name [3] 258131 0
Horphag Research
Address [3] 258131 0
PO Box 80
Cointrin/GENEVA
CH-1216
Country [3] 258131 0
Switzerland
Primary sponsor type
University
Name
Swinburne University of Technology
Address
Centre for Human Psychopharmacology, Swinburne University of Technology, Advanced Technology Centre 427-451 Burwood Rd, Hawthorn, Victoria, 3122
Country
Australia
Secondary sponsor category [1] 257304 0
None
Name [1] 257304 0
Address [1] 257304 0
Country [1] 257304 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 260110 0
Swinburne University Human Research Ethics
Ethics committee address [1] 260110 0
Swinburne University PO Box 218 HAWTHORN
VIC 3122
Ethics committee country [1] 260110 0
Australia
Date submitted for ethics approval [1] 260110 0
Approval date [1] 260110 0
14/07/2010
Ethics approval number [1] 260110 0
2010/106

Summary
Brief summary
This study will investigate the effects of chronic administration of two natural supplements on cognition, cardiovascular function and biological measures, in comparison to a placebo.
The primary aim of this project is to determine whether 12 months administration of the natural supplements Bacopa monniera (EBm) and Pycnogenol (PYC) improve cognitive functioning in a healthy older population. The secondary aims of this project are to investigate the mechanisms underpinning any cognitive effects of EBm and PYC by examining the relationship between cognition, biochemical, neuroimaging and cardiovascular measures and to investigate the time course of any improvements. The study will follow a double-blind, randomised, placebo-controlled, between-group design.
Participants will be required to consume one of three types of supplements (EBm, PYC, or placebo) daily for 12-months. We will measure performance on different cognitive tasks, mood, brain imaging (for a sub-group of participants), gut microbiota (for a sub-group of participants), cardiovascular and biochemical measures before treatment (baseline), 3-months, 6-months and 12-months after consuming the treatment.

In addition, as a sub-study to the main project 150 participants will be recruited to take part only in baseline assessments. The participants will undergo the same measures (excluding brain imaging) as for the main study, but will not receive any intervention and will not be required to attend follow-up assessments. This sub-study will allow further exploration of the relationship between GI microbiota and the other outcome measures including cognition, mood and cardiovascular function.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31898 0
Prof Con Stough
Address 31898 0
Mailbox H24
Centre for Human Psychopharmacology
Swinburne University of Technology
PO Box 218
Hawthorn
VIC 3122
Country 31898 0
Australia
Phone 31898 0
+61 3 9214 8167
Fax 31898 0
Email 31898 0
cstough@gmail.com
Contact person for public queries
Name 15145 0
Dr Naomi Perry
Address 15145 0
Mailbox H24
ATC1014
Centre for Human Psychopharmacology
Swinburne University of Technology
PO Box 218
Hawthorn
VIC 3122
Country 15145 0
Australia
Phone 15145 0
+61 3 9214 8930
Fax 15145 0
Email 15145 0
nlperry@swin.edu.au
Contact person for scientific queries
Name 6073 0
Prof Prof Con Stough
Address 6073 0
Centre for Human Psychopharmacology, Swinburne University of Technology, Level 10 Advanced Technology Centre 427-451 Burwood Rd, Hawthorn, Victoria, 3122
Country 6073 0
Australia
Phone 6073 0
+61 3 9214 8167
Fax 6073 0
+61 3 9214 5525
Email 6073 0
cstough@swin.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment
It is expected that the results of this trial will be published in peer reviewed journals and student theses, as well as being presented 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.
What supporting documents are/will be available?
No other documents available
Summary results
No Results