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Trial registered on ANZCTR


Registration number
ACTRN12617000305325
Ethics application status
Approved
Date submitted
23/02/2017
Date registered
27/02/2017
Date last updated
19/06/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of 4 weeks supplementation with a multi-vitamin/mineral preparation on neurocognitive function in healthy adults
Scientific title
Effects of 4 weeks supplementation with a multi-vitamin/mineral preparation on neurocognitive function in healthy adults: A randomised, double-blind, placebo controlled trial
Secondary ID [1] 291257 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mood 302189 0
Cognitive Function 302190 0
Condition category
Condition code
Mental Health 301799 301799 0 0
Studies of normal psychology, cognitive function and behaviour
Neurological 301800 301800 0 0
Studies of the normal brain and nervous system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be randomly assigned to one of the following treatments:

1)Berocca Performance (registered trademark)
2)Placebo: Matched for appearance, taste and smell.

Treatments will be administered in the form of effervescent tablets.

Participants will be instructed to take one tablet daily, dissolved in a glass of water (approx 200 ml) for a duration of 28 days. Treatment adherence will be monitored by the use of a compliance log which participants will take home with them and record the time at which they take their tablet 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 tablets at the completion of the study so that the experimenter can confirm that the number of tablets they have taken is in agreement with their log. The count of returned treatments will be used for compliance where these measures disagree.

Each daily dose of Active treatment (Berocca Performance) contains:

Vitamin C 500mg
Thiamine Monophosphoric acid ester chloride 18.54mg
Riboflavin (Vitamin B2) 15mg
Nicotinamide (B3/niacin) 50mg
Vitamin B5 23mg
Vitamin B6 10mg
Vitamin B12 0.01mg
Folic Acid (Vitamin B9) 0.4mg
Biotin (Vitamin B7) 0.15mg
Calcium 100mg
Magnesium 100mg
Zinc 10mg
Intervention code [1] 297261 0
Treatment: Other
Comparator / control treatment
Placebo, matched for appearance, taste and smell.
Control group
Placebo

Outcomes
Primary outcome [1] 301200 0
Everyday mood - Assessed by Profile of Mood States
Timepoint [1] 301200 0
Follow-up assessment after 28 days of treatment
Primary outcome [2] 301201 0
Functional brain activity during completion of the Rapid Visual Information Processing task (fMRI BOLD response; within the cohort of participants completing the MRI assessment (n=40)).
Those amongst the study population who indicate willingness to participate in this MRI component and fit safety criteria for MRI will be selected for this assessment (see exclusion criteria 10, 11, 12). This will be offered to all participants, until the sub-group is filled (n=40).
Timepoint [2] 301201 0
Follow-up assessment after 28 days of treatment
Secondary outcome [1] 332019 0
Cognitive performance during completion of the Multi-Tasking Framework.
Timepoint [1] 332019 0
Follow-up assessment after 28 days of treatment
Secondary outcome [2] 332020 0
Self-rated stress, as assessed by the Perceived Stress Scale
Timepoint [2] 332020 0
Follow-up assessment following 28-days treatment
Secondary outcome [3] 332022 0
Stress reactivity in response to Cognitive Demand Battery and Multi-Tasking Framework assessed using composite score from State-Trait Anxiety Inventory - State scale and stress visual analogue scales,
Timepoint [3] 332022 0
Follow-up assessment after 28-days of treatment
Secondary outcome [4] 332023 0
Survey of Subjective Effects (3 semi-structured questions probing any perceived positive, negative and unusual changes in physical or mental functioning), designed for this study.
Timepoint [4] 332023 0
Follow-up assessment following 28-days treatment
Secondary outcome [5] 332024 0
Hematological measures:
B2, B6, Red Cell Folate, B12, homocysteine, protein carbonyl content
Timepoint [5] 332024 0
Follow-up assessment following 28-days treatment
Secondary outcome [6] 332025 0
MRI cohort only (n=40)
Cerebral Metabolic Rate of Oxygen Consumption (using T2 relaxation under spin tagging + phase contrast MRI)
Timepoint [6] 332025 0
Follow-up assessment following 28-days treatment
Secondary outcome [7] 332078 0
Cognitive performance during completion of the Cognitive Demand Battery
Timepoint [7] 332078 0
Follow-up assessment following 28-days treatment
Secondary outcome [8] 332079 0
Perceived workload in response to significant cognitive demand, assessed using NASA-Task Load Index.
Timepoint [8] 332079 0
Follow-up assessment following 28-days treatment
Secondary outcome [9] 332080 0
Mood reactivity to Cognitive Demand and Multi-Tasking Framework, assessed using Bond-Lader Visual Analogue Mood scale.
Timepoint [9] 332080 0
Follow-up assessment following 28-days treatment
Secondary outcome [10] 332081 0
Fatigue in response to Cognitive Demand Battery and Multi-Tasking Framework, assessed from Fatigue visual Analogue Scales.
Timepoint [10] 332081 0
Follow-up assessment following 28-days treatment
Secondary outcome [11] 332082 0
MRI cohort only (n=40)
Neurometabolite change (NAA, ch, cr, MI) using Magnetic Resonance Spectroscopy of Posterior Cingulate (PRESS sequence, 30 TE)
Timepoint [11] 332082 0
Follow-up assessment following 28-days treatment
Secondary outcome [12] 332083 0
Cardiovascular function (Arterial Stiffness)
- pulse wave velocity using the SphygmoCor system
Timepoint [12] 332083 0
Follow-up assessment following 28-days treatment

Eligibility
Key inclusion criteria
1. Healthy, non-smoking, males and females aged 18-40.
2. Are comfortable with computers and MRI and willing and able to participate in all scheduled visits, treatment plan, tests and other trial procedures according to the protocol.
3. Provide a personally signed and dated informed consent indicating that the participant has been informed of all pertinent aspects of the trial.
4. For participants in the MRI condition, only right handed participants will be recruited
5. Female subjects of childbearing age using an acceptable form of contraception (including hormonal methods (eg. oral contraceptive, hormonal implants), barrier methods (eg. male or female condom, diaphragm) or abstinence).
6. Fluent in spoken and written English
Minimum age
18 Years
Maximum age
40 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. History, or current diagnosis, of anxiety, depression, other psychiatric disorders, or dementia.
2. History of / currently suffering from heart disease, high blood pressure or diabetes
3. Taking any medication, herbal extracts, vitamin supplements or illicit drugs within 4 weeks prior to (and duration of) study reasonably expected to affect the outcomes of the trial or interact with investigational products (routine medications to treat benign conditions, such as antibiotics to treat acne, are permissible)
4. Health conditions that would affect food metabolism including the following: food allergies, kidney disease, liver disease and/or gastrointestinal diseases (e.g. Irritable bowel syndrome, coeliac disease, peptic ulcers)
5. History of serious head trauma, epilepsy or other neurological condition
6. Renal function problems, Hypercalcaemia; Hypermagnesemia, Severe hypercalciuria, phenylketonuria (autosomal metabolic disorder)
7. Currently pregnant or lactating
8. Participation in another trial within 30 days prior to the start of the study.
9. Hypersensitivity to the investigational product or any of the active/inactive ingredients
10. Any condition which may interfere with the subject’s ability to perform assessments (e.g. claustrophobia for the MRI arm, dyslexia).
11. People with metal implants (for MRI component only)
12. Left handed participants (for MRI component only).
13. Excessive alcohol consumption consistent with harmful or hazardous drinking, or alcohol use disorder

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)
Screening for eligibility will be conducted prior to randomisation. Subjects who meet all inclusion and exclusion criteria will be randomised according to the randomisation schedule - generated by a disinterested third party such that investigators remain blind to allocation.

Randomisation numbers will be assigned in ascending numerical order according to appearance at the study site on the day subjects are randomised.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A disinterested third party will generate the randomisation sequence using a computerised sequence generator.

Randomization sequences will be stratified by gender and assessment protocol (MRI sub-group), in order to balance treatment assignments for males and females and within the MRI sub-component.
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
Efficacy
Statistical methods / analysis
Based on the reported eta squared =.11 obtained from a previous trial with this intervention in a similar population (White et al., 2015), we anticipate a medium to large effect size for this outcome (f=.352). At an alpha rate of .05, the study would require 66 participants, a total of 33 per treatment arm to obtain power =.80 in detecting this effect size. Accounting for drop-outs and other data loss, the study originally aimed to recruit 40 participants per treatment arm (n=80). The planned sample size was extended based on a desire to be sufficiently powered for the cognitive performance secondary outcomes (Multi-Tasking Framework), to enable the trial to be powered for these outcomes. Based on a previous trial with same MTF cognitive outcome, which reported a treatment effect with a Cohen's d = 0.5431, it was determined the study will require 109 participants to obtain power =.80 at an alpha rate of .05. In order to account for dropouts and other data loss order, the study will recruit 130 participants attending baseline assessment (~15-20% attrition and data loss). Based on the effect size observed on the depression-dejection outcome described above, this sample size provides 95% power for the mood primary outcome, whilst providing 80% power for the secondary cognitive outcome.

The primary analysis will be done on the per protocol population. All participants selected for analyses must have completed the whole study and have a suitable level of compliance. Any participants with data that inexplicably varies widely from the rest of their treatment group will be excluded from analyses. Screening of data will be completed while blind to treatment allocation, as part of a blind data review meeting.

Primary analysis of outcomes will examine scores for cognitive, mood, cardiovascular and nutritional status measures, using ANCOVA analyzing between groups effect of treatment on post-treatment scores, using baseline scores as a covariate. The impact of additional baseline variables, including fruit and vegetable intake, will also be studied by including as a covariate in outcome analysis. Post-hoc analysis will be conducted where appropriate using Bonferroni correction.

For the functional brain activity outcome, primary analyses will pursue Regions of Interest defined from pilot data obtained during the previous trial (see White et al., 2016, doi: 10.3389/fnagi.2016.00288), including bilateral parietal regions, supplementary motor and frontal areas. Follow-up whole-brain analysis of treatment effects will utilize second-level random effects 2 x 2 ANOVA including visit (baseline, post-treatment) and treatment group (placebo, Berocca), with subject included as a factor in the design matrix. Whole-brain analyses will be conducted using a Family-Wise Error corrected threshold of p<.05 to control for multiple comparisons

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
6/03/2017
Actual
30/03/2017
Date of last participant enrolment
Anticipated
22/11/2017
Actual
13/04/2018
Date of last data collection
Anticipated
22/12/2017
Actual
11/05/2018
Sample size
Target
130
Accrual to date
Final
130
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 295712 0
Commercial sector/Industry
Name [1] 295712 0
Bayer Consumer Care AG
Country [1] 295712 0
Switzerland
Primary sponsor type
University
Name
Swinburne University
Address
PO Box 218
Hawthorn,
VIC, 3122
Country
Australia
Secondary sponsor category [1] 294560 0
None
Name [1] 294560 0
Address [1] 294560 0
Country [1] 294560 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297015 0
Swinburne University Human Research Ethics Committee
Ethics committee address [1] 297015 0
Ethics committee country [1] 297015 0
Australia
Date submitted for ethics approval [1] 297015 0
25/11/2016
Approval date [1] 297015 0
21/02/2017
Ethics approval number [1] 297015 0
SHR Project 2016/312

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

Contacts
Principal investigator
Name 72726 0
Prof Andrew Scholey
Address 72726 0
Centre for Human Psychopharmacology,
Swinburne University,
Mail H24
PO Box 218
Hawthorn
VIC, 3122
Country 72726 0
Australia
Phone 72726 0
+61 3 92148932
Fax 72726 0
Email 72726 0
andrew@scholeylab.com
Contact person for public queries
Name 72727 0
David White
Address 72727 0
Centre for Human Psychopharmacology,
Swinburne University,
Mail H24
PO Box 218
Hawthorn
VIC, 3122
Country 72727 0
Australia
Phone 72727 0
+61 3 92145341
Fax 72727 0
Email 72727 0
dawhite@swin.edu.au
Contact person for scientific queries
Name 72728 0
David White
Address 72728 0
Centre for Human Psychopharmacology,
Swinburne University,
Mail H24
PO Box 218
Hawthorn
VIC, 3122
Country 72728 0
Australia
Phone 72728 0
+61 3 92145341
Fax 72728 0
Email 72728 0
dawhite@swin.edu.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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