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Trial registered on ANZCTR


Registration number
ACTRN12616000732482
Ethics application status
Approved
Date submitted
26/05/2016
Date registered
3/06/2016
Date last updated
1/07/2019
Date data sharing statement initially provided
1/07/2019
Date results information initially provided
1/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Cardiometabolic and cognitive benefits of omega-3 polyunsaturated fatty acids and curcumin supplementation in older, sedentary and overweight/obese adults
Scientific title
Cardiometabolic and cognitive benefits of omega-3 polyunsaturated fatty acids and curcumin supplementation in older, sedentary and overweight/obese adults
Secondary ID [1] 289312 0
Nil known
Universal Trial Number (UTN)
U1111-1183-2927
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obesity 298912 0
Condition category
Condition code
Cardiovascular 298982 298982 0 0
Diseases of the vasculature and circulation including the lymphatic system
Diet and Nutrition 298983 298983 0 0
Obesity
Mental Health 298984 298984 0 0
Studies of normal psychology, cognitive function and behaviour

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A 16-week randomised, double-blind, placebo-controlled, 4-arm parallel dietary intervention trial. Participants will be assigned to one of four treatment groups: Group 1: Placebo only; Group 2: Fish oil+ placebo; Group 3: Curcumin + placebo; Group 4: Fish oil + curcumin. The daily dose for fish oil is 4 x 1g (500mg DHA: 100mg EPA) and 2 x 400mg of curcumin. Volunteers will be required to consume their allocated supplement capsules twice a day with meals and note the time of consumption in their supplement diary.
Intervention code [1] 294866 0
Treatment: Drugs
Comparator / control treatment
Placebo: Corn oil. Placebo: Dextrin and a small amount of (approx 4mg per capsule) tartrazine (E102) for colouring to visually match the active capsule.
Control group
Placebo

Outcomes
Primary outcome [1] 298458 0
To determine in overweight/obese and sedentary older adults the effects of 16-week supplementation with DHA-rich fish oil (Omega Brain) and curcumin (Brain Active), alone or in combination, on CVR to hypercapnia, assessed by transcranial doppler (TCD) ultrasound.
Timepoint [1] 298458 0
Week 0 and 16 weeks post intervention commencement.
Secondary outcome [1] 324201 0
Composite secondary outcome: To determine the effects of supplementation on other indices of cerebrovascular function (basal cerebral haemodynamics and neurovascular coupling, as measured by CVR to cognitive test battery and photic stimuli). Assessed by TCD ultrasound.
Timepoint [1] 324201 0
Week 0 and 16 weeks post intervention commencement.
Secondary outcome [2] 324366 0
Composite secondary outcome: To determine the effects of supplementation on mood, assessed by the Profile of Mood States (POMS) questionnaire, the Center for Epidemiological Studies Depression Scale (CES-D) and the NIH Toolbox Perceived Stress Scale (PSS).
Timepoint [2] 324366 0
Week 0 and 16 weeks post intervention commencement.
Secondary outcome [3] 324367 0
To determine the effects of supplementation on cognitive function, assessed by cognitive test battery, The neuropsychological test battery will consist of the Trail Making Task (measure of attentional and executive functions, which becomes impaired with age), the N-back task, Block design test (measure of visuospatial), reaction time test (Go-No-Go) and the NIH Toolbox Battery of cognitive function.
Timepoint [3] 324367 0
Week 0 and 16 weeks post intervention commencement.
Secondary outcome [4] 324368 0
To determine the effects of supplementation on cardiovascular risk factors (plasma lipids, assessed by plasma assay; clinic blood pressure, assessed using sphygmomanometry and arterial compliance assessed using a Cardiovascular Profiler.
Timepoint [4] 324368 0
Week 0 and 16 weeks post intervention commencement.
Secondary outcome [5] 324369 0
To determine the effects of supplementation on metabolic markers (fasting plasma glucose, insulin, insulin sensitivity, inflammatory cytokines and CRP) assessed by plasma assay.
Timepoint [5] 324369 0
Week 0 and 16 weeks post intervention commencement.
Secondary outcome [6] 324370 0
To determine the effects of supplementation on overall wellbeing (pain and quality of life), assessed by QoL questionnaire (using the SF-36) and McGill pain questionnaire.
Timepoint [6] 324370 0
Week 0 and 16 weeks post intervention commencement.
Secondary outcome [7] 324377 0
Correlation between cognition and plasma curcumin and Omega-3 Index (O3I). Assessed using cognitive test battery and plasma assay and serum assay.
Timepoint [7] 324377 0
Week 0 and 16 weeks post intervention commencement.
Secondary outcome [8] 324378 0
Correlation between mood and plasma curcumin and Omega-3 Index (O3I). Assessed by the Profile of Mood States (POMS) questionnaire, the Center for Epidemiological Studies Depression Scale (CES-D) and the NIH Toolbox Perceived Stress Scale (PSS) and plasma and serum assay.
Timepoint [8] 324378 0
Week 0 and 16 weeks post intervention commencement.
Secondary outcome [9] 324379 0
Correlation between overall well-being (quality of life and pain )and plasma curcumin and Omega-3 Index (O3I). Assessed using QoL questionnaire (using the SF-36), the McGill Pain questionnaire and plasma and serum assay.
Timepoint [9] 324379 0
Week 0 and 16 weeks post intervention commencement.
Secondary outcome [10] 324380 0
Correlation between cerebrovascular function and plasma curcumin and Omega-3 Index (O3I). Assessed using TCD ultrasound and plasma and serum assay.
Timepoint [10] 324380 0
Week 0 and 16 weeks post intervention commencement.
Secondary outcome [11] 324381 0
To determine if changes in neurovascular coupling capacity following supplementation are related to cognitive performance. Assessed by TCD ultrasound and cognitive test battery.
Timepoint [11] 324381 0
Week 0 and 16 weeks post intervention commencement.

Eligibility
Key inclusion criteria
Age 50-80 years old (women must be >12 months postmenopausal)
BMI 25-40kg/m2
Self-reported physical activity level <150min per week
Consuming < 2 fish/seafood meals per week
Consuming up to 300mg/d of LCn-3 PUFA from fish oil supplements or enriched foods
No change in medication type or dose for 1 month before the intervention
Minimum age
50 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Clinic BP >160mmHg systolic or 100mmHg diastolic (determined at screening)
Suspected dementia (ACE-III score <82/100)
Smokers or currently on nicotine therapy
Neurological conditions
Heart/kidney/liver disease
Insulin therapy
Regularly consuming more than four standard alcoholic drinks per day
Major depression as diagnosed by a health care professional
Illiterate
Unwilling to maintain pre-enrolment physical activity levels and dietary habits for the duration of the trial
Unwilling to refrain from consuming stimulants before each clinic visit
Unwilling to provide a blood sample
Have any other medical condition or treatments (including supplements) which, in the investigators’ opinion, may confound the outcome of the study.

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)
Concealment by numbered containers
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Allocation to either treatment phase is based on the minimisation method (BMI and age) to ensure well-balanced groups.
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
A 16-week randomised, double-blind, placebo-controlled, 4-arm parallel dietary intervention trial.
Phase
Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Baseline measures of age, O3I, years of education and scores on the ACE-III and other potentially confounding variables may be added as covariates if they are significantly correlated with the outcome measures.
Pre-supplementation data obtained at the screening/baseline visit 1 and 2 will be used in regression analysis to evaluate the associations between outcome measures. The correlations may include the relationships between cerebrovascular function (arterial stiffness, basal cerebral hemodynamics and CVR to hypercapnia, cognitive and photic stimuli) and cognitive performance, clinic BP and AC, 24-ABP, mood, pain, overall wellbeing and cardiometabolic biomarkers including O3I.
In an intention-to-treat analysis, effects of LCn-3PUFA supplementation on primary and secondary outcomes will be analysed by two-way, repeated measures ANOVA with factors of time (baseline, post-dose) and treatment (placebo, LCn-3PUFA). Significant interactions (with appropriate correction for multiple comparisons) will be further explored by pre-planned comparisons of treatments at each time point using t-tests for independent samples.
Baseline measures will be used as covariates. We will match groups by stratification of age, gender, BMI (overweight or obese categories), O3I and other potentially confounding variables such as global cognition and years of education will be added as covariates.
Relationships between changes in circulatory parameters and cognitive parameters will be analysed by linear regression with appropriate pre-planned Bonferroni comparisons and the effect of biomarker status will be determined using biomarkers as covariates in a mixed model analysis.
134 participants in a four-treatment arm design will give 80% power to detect a 8% change in CVR to hypercapnia (relative increase ~25%) at alpha = 0.05, based on a 8% SD observed previously. We will recruit a total of 160 participants to allow for 20% attrition.

Recruitment
Recruitment status
Completed
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)
NSW

Funding & Sponsors
Funding source category [1] 293690 0
Commercial sector/Industry
Name [1] 293690 0
Blackmores Ltd.
Address [1] 293690 0
20 Jubilee Avenue
Warriewood NSW 2102
Country [1] 293690 0
Australia
Primary sponsor type
Individual
Name
Professor Peter Howe
Address
Clinical Nutrition Research Centre
MS122a
School of Biomedical Sciences & Pharmacy
University of Newcastle
University Drive
Callaghan, New South Wales 2308
Country
Australia
Secondary sponsor category [1] 292523 0
None
Name [1] 292523 0
Address [1] 292523 0
Country [1] 292523 0
Other collaborator category [1] 279008 0
Individual
Name [1] 279008 0
Dr Rachel Wong
Address [1] 279008 0
Clinical Nutrition Research Centre
MS514
School of Biomedical Sciences & Pharmacy
University of Newcastle
University Drive
Callaghan, New South Wales 2308
Country [1] 279008 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295128 0
University of Newcastle Human Research Ethics Committee
Ethics committee address [1] 295128 0
Chancellery
University of Newcastle
University Drive
Callaghan, New South Wales 2308
Ethics committee country [1] 295128 0
Australia
Date submitted for ethics approval [1] 295128 0
30/05/2016
Approval date [1] 295128 0
12/09/2016
Ethics approval number [1] 295128 0
H-2016-0170

Summary
Brief summary
Lifestyle risk factors such as lack of regular exercise, poor diet, ageing, excess body weight, high blood fats and high blood sugar levels can lead to overall inflammation, narrowing and hardening of arteries, thus reducing the ability of blood vessels to dilate effectively. A consequence of ineffective dilation of blood vessels is poor blood flow in the brain and this can lead to memory problems, poor concentration or mood.
Certain ingredients from food sources such as the long-chain Omega-3 polyunsaturated fatty acids in fish and fish oil are known to benefit heart health by increasing the elasticity of blood vessels, as well as boosting mood and mental performance. Recently, curcumin from the spice turmeric which gives curry its yellow colour is gaining attention for its anti-inflammatory activities. We believe that curcumin can reduce inflammation and in turn enhance blood vessel function. However, their direct effects on the blood vessels in the brain and resultant impact on mental performance are unknown.
In this study, we are looking to determine whether supplementing the diet with fish oil or curcumin or a combination of the two nutrients for 16 weeks can enhance the ability of blood vessels in the brain to dilate. We will also explore its effects on blood pressure, blood fats, glucose and markers of inflammation, stiffness of blood vessels, pain, quality of life, mood and mental performance.
WHAT ARE THE AIMS OF THIS STUDY?
We aim to determine if 16 weeks of fish oil and/or curcumin supplementation can:
A. enhance blood flow in the brain in response to demands and thereby improve mood and mental abilities such as short-term memory, attention and concentration
B. enhance perception of quality of life.
C. reduce perception of pain and stress
D. reduce inflammation, blood sugar levels and blood fats.
We are seeking a total of 160 overweight or obese men and post-menopausal women who have not had their period for at least 12 months, age 50 – 80 years old and who are relatively inactive (for example less than 150 minutes of exercise on average per week).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 66210 0
Prof Peter Howe
Address 66210 0
Clinical Nutrition Research Centre MS122a School of Biomedical Sciences & Pharmacy University of Newcastle University Drive Callaghan, New South Wales 2308
Country 66210 0
Australia
Phone 66210 0
+61 2 4921 7309
Fax 66210 0
Email 66210 0
Peter.Howe@newcastle.edu.au
Contact person for public queries
Name 66211 0
Prof Peter Howe
Address 66211 0
Clinical Nutrition Research Centre MS122a School of Biomedical Sciences & Pharmacy University of Newcastle University Drive Callaghan, New South Wales 2308
Country 66211 0
Australia
Phone 66211 0
+61 2 4921 7309
Fax 66211 0
Email 66211 0
Peter.Howe@newcastle.edu.au
Contact person for scientific queries
Name 66212 0
Prof Peter Howe
Address 66212 0
Clinical Nutrition Research Centre MS122a School of Biomedical Sciences & Pharmacy University of Newcastle University Drive Callaghan, New South Wales 2308
Country 66212 0
Australia
Phone 66212 0
+61 2 4921 7309
Fax 66212 0
Email 66212 0
Peter.Howe@newcastle.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary