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Trial registered on ANZCTR

Registration number

ACTRN12615000956505

Ethics application status

Approved

Date submitted

25/08/2015

Date registered

11/09/2015

Date last updated

4/12/2018

Date data sharing statement initially provided

4/12/2018

Date results provided

4/12/2018

Type of registration

Retrospectively registered

Titles & IDs

Public title

Plant sterols and Curcumin for the Prevention of Cardiovascular Disease

Scientific title

Complementary and/or synergistic effects of phytosterols and curcumin on cardiovascular disease risk factors in hypercholesterolaemic adults.

Secondary ID [1]

Nil known

Universal Trial Number (UTN)

U1111-1173-6120

Trial acronym

PAC-CVD Trial

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Hypercholesterolaemia

Inflammation

Cardiovascular disease

Condition category

Condition code

Cardiovascular

Other cardiovascular diseases

Diet and Nutrition

Other diet and nutrition disorders

Inflammatory and Immune System

Other inflammatory or immune system disorders

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

The effects of dietary supplementation of 2.0g of phytosterols (phytosterol-enriched margarine) with or without curcumin (capsules) each day. This randomised control trial is a 2x2 factorial placebo-controlled design.
Hypercholesterolaemic individuals will be randomly assigned to one of the following treatment arms for 4 weeks:
Arm 1: Placebo: 25g Regular canola-based margarine spread plus placebo (2 x 500mg capsules) per day.
Arm 2: 25g Logicol margarine spread (i.e. 2g phytosterols) plus placebo (2 x 500mg capsules) per day.
Arm 3: 25g Regular canola-based margarine spread plus Curcumin (2 x 500mg capsules) per day.
Arm 4: 25g Logicol margarine spread (i.e. 2g phytosterols) and Curcumin (2x 500mg capsules) per day.

The margarine will be pre-weighed into individual containers containing the daily dosage and all of the daily dose of margarine (i.e. 25g) is to be consumed. Participants will be instructed on how to consume the margarine at their initial visit to the research clinic. The margarine is to be consumed as a regular margarine or butter spread would normally be used (i.e. spread on bread, crackers, muffins etc) however, not used for cooking or melted on top of vegetables.

To assess compliance:
1. Participants will be asked to record their daily consumption of the two intervention products in a standardised log provided to them.
2. Participants will be asked to return all margarine containers and capsule bottles at the end of the trial for record and weighing of any remaining products.

Intervention code [1]

Treatment: Other

Intervention code [2]

Prevention

Comparator / control treatment

Phytosterol placebo - low-fat, canola-based margarine (commercially available)
Curcumin placebo capsules - microcrystalline cellulose and dicalcium phosphate anhydrous

Control group

Placebo

Outcomes

Primary outcome [1]

Total cholesterol concentration in blood plasma

Timepoint [1]

At baseline (week zero) and at week 4 (end of study)

Primary outcome [2]

Low-density lipoprotein cholesterol concentration in blood plasma

Timepoint [2]

At baseline (week zero) and at week 4 (end of study)

Secondary outcome [1]

Inflammatory mediators (i.e. CRP, fibrinogen, IL-6, IL-1beta, IkB, iCAM)

Timepoint [1]

At baseline (week zero) and week 4 (end of study)

Secondary outcome [2]

Cardiovascular Disease Risk - using the Framingham cardiovascular disease risk algorithm.

Timepoint [2]

At baseline (week zero) and week 4 (end of study)

Eligibility

Key inclusion criteria

* Age: 18-70 years
* Gender: both males and females
* Total cholesterol levels greater than or equal to 5.5mmol/L (after a 10 hour fast)

Minimum age

18 Years

Maximum age

70 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

* Pregnant or lactating
* History of cardiovascular events (e.g. stroke, heart attack, angina, aneurysm, hemorrhage, myocardial infarction etc)
* People with pace maker implants
* Diabetes mellitus
* A chronic inflammatory disease and/or condition (e.g. cancer)
* Hypertension
* Liver or renal disease
* Taking anti-inflammatory medications/supplements (e.g. Aspirin, Atacand, Celebrex)
* Taking hypolipidaemic medications/supplements (e.g. Lipitor, Crestor, Zocor)
* Taking regular dietary supplements known to influence blood lipid levels (e.g. fish oil, fibre, curcumin)
* Already consuming phytosterol-enriched products on a daily and/or regular basis (approximately 4 days/week)
* Strong allergies/intolerance/sensitivities or food aversions to the foods involved in this study
* History of gastric ulcers, lung and respiratory diseases
* History of severe neurological diseases or seizures
* BMI greater than 40

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)

Interested subjects will contact the study investigator who will then assess the subject's eligibility to participate over the phone. If the participant is deemed eligible, the participant will be sent a consent form, participant information statement and will be enrolled in the study. They will also be sent a series of self-administered questionnaires (medical history, physical activity, 3-day food record) along with instructions. All forms will need to be completed and returned upon baseline visit.
Allocation to treatments will be based on the computer generated block randomization method to ensure well-balanced groups. The allocation concealment will be conducted using sealed opaque envelopes.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Allocation to treatments will be based on the computer generated block randomization method to ensure well-balanced groups.

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Factorial

Other design features

Phase

Not Applicable

Type of endpoint/s

Efficacy

Statistical methods / analysis

Sample size determination:
Twenty participants in a 2x2 factorial study design will give 80% power to detect a 10% drop in total cholesterol levels at alpha = 0.05. We will recruit 4x20 = 80 participants according to the inclusion criteria.

Baseline data:
Baseline measures will be used as covariates. Gender, age and other potentially confounding variables such as anthropometrics, physical activity levels, and duration of hypercholesterolaemia may be added as covariates if they are significantly correlated with the outcome measures.

Treatment effects:
All the data relating the significant effects of phytosterols and/or curcumin will be expressed as mean+/- SEM. The effect of interventions on blood lipids and pro-inflammatory markers between groups will be estimated using two-way ANOVA with post-hoc comparisons (Tukey’s significant difference). Significance (P-value set at 0.05) indicates the changes from the baseline values. Changes from baseline will be determined using non-parametric analysis (Wilcoxon’s signed ranked test). This statistical analysis will help to determine whether there will be a significant main effect for each independent variable by testing for between subject effects. The statistical analysis by this method will be performed to evaluate the synergistic effects between Phytosterols and Curcumin.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

7/09/2015

Actual

7/09/2015

Date of last participant enrolment

Anticipated

Actual

28/10/2016

Date of last data collection

Anticipated

Actual

2/12/2016

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment postcode(s) [1]

2308 - Newcastle University

Recruitment postcode(s) [2]

2300 - Newcastle

Funding & Sponsors

Funding source category [1]

Self funded/Unfunded

Name [1]

Address [1]

Country [1]

Primary sponsor type

University

Name

University of Newcastle

Address

University Drive
Callaghan, NSW
2308

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Human Research Ethics Committee

Ethics committee address [1]

The Chancellery 
The University of Newcastle 
University Drive
Callaghan NSW 2308

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

25/08/2015

Ethics approval number [1]

H-2015-0162

Summary

Brief summary

Cardiovascular disease (CVD) is the leading cause of death worldwide.Two major risk factors for CVD are high levels of blood cholesterol and inflammation. It is well known that dietary supplementation with foods enriched with plant sterols lower cholesterol levels by 10% in 3 weeks. It is also known that curcumin (found in tumeric) has anti-inflammatory properties. This project aims to investigate if combined dietary supplementation with plant sterols and curcumin reduces blood cholesterol and inflammation to a larger extent than either of the treatments alone.It is expected that participants will have improved levels of blood cholesterol, fatty acids and markers of inflammation as well as an overall reduced 10-year risk of developing CVD. The findings of this research could translate to wider public health benefits through the development of a single functional food that combines both phytosterols and curcumin (e.g. margarine spread or reduced-fat milk). This could be easily incorporated into the regular diet of the general Australian adult population in order to minimise the risk of developing cardiovascular disease.

Trial website

Trial related presentations / publications

Publication: Ferguson JJA, Stojanovski E, MacDonald-Wicks L and Garg ML. Curcumin potentiates cholesterol-lowering effects of phytosterols in hypercholesterolaemic individuals. A randomised controlled trial. Metabolism - Clinical & Experimental. 2018;82:22-35

Presentations; 
ORAL: ‘Curcumin enhances cholesterol-lowering potential of phytosterols in hypercholesterolaemic individuals: A randomized controlled trial.’ 13th Congress of the International Society For the Study of Fatty Acids and Lipids (ISSFAL). Las Vegas, United Sates. May 2018.

POSTER: ‘Lipid-lowering effects of phytosterols and/or curcumin in hypercholesterolaemic individuals: a randomized controlled trial.’ 10th Asia Pacific Conference on Clinical Nutrition. Adelaide, Australia. November 2017.

ORAL: ‘Synergistic effects of phytosterols and curcumin to reduce cardiovascular disease risk in hypercholesterolaemic individuals.’ 2017 Australian Atherosclerosis Society Annual Meeting. Sydney, Australia. October 2017.

Public notes

Contacts

Principal investigator

Name

Prof Manohar Garg

Address

Nutraceuticals Research Group
305C Medical Science Building
University of Newcastle
University Drive
Callaghan, NSW 2308

Country

Australia

Phone

+61-2-4921 5647

Fax

+61-2-4921 2028

[email protected]

Contact person for public queries

Name

Manohar Garg

Address

Nutraceuticals Research Group
305C Medical Science Building
University of Newcastle
University Drive
Callaghan, NSW 2308

Country

Australia

Phone

+61-2-4921 5647

Fax

+61-2-4921 2028

[email protected]

Contact person for scientific queries

Name

Manohar Garg

Address

Nutraceuticals Research Group
305C Medical Science Building
University of Newcastle
University Drive
Callaghan, NSW 2308

Country

Australia

Phone

+61-2-4921 5647

Fax

+61-2-4921 2028

[email protected]

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?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Association of Plasma Neurofilament Light Chain With Glycaemic Control and Insulin Resistance in Middle-Aged Adults.	2022	https://dx.doi.org/10.3389/fendo.2022.915449

N.B. These documents automatically identified may not have been verified by the study sponsor.

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