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Trial registered on ANZCTR


Registration number
ACTRN12618001960246
Ethics application status
Approved
Date submitted
23/11/2018
Date registered
4/12/2018
Date last updated
4/12/2018
Date data sharing statement initially provided
4/12/2018
Date results information initially provided
4/12/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Plant sterols and Curcumin for Reducing Heart Disease Risk
Scientific title
Phytosterol and/or curcumin enriched bread modulates lipoprotein profile in hypercholesterolaemic individuals. A randomised controlled trial
Secondary ID [1] 296692 0
Nil known
Universal Trial Number (UTN)
Trial acronym
PAC-FOOD Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypercholesterolaemia 310537 0
Dyslipidaemia 310538 0
Condition category
Condition code
Cardiovascular 309247 309247 0 0
Other cardiovascular diseases
Diet and Nutrition 309248 309248 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The effects of dietary supplementation with a bread enriched with 2.5g of phytosterols with or without 228mg curcumin 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: x2 slices/day of white bread containing no Phytosterols and no Curcumin.
Arm 2: PS: x2 slices/day of white bread containing 2.5g Phytosterols and 0mg Curcumin.
Arm 3: CC: x2 slices/day of white bread containing 0g Phytosterols and 228mg Curcumin.
Arm 4: PS-CC: x2 slices/day of white bread containing 2.5g Phytosterols and 228mg Curcumin.
*Phytosterols are delivered as Vegapure 67 WDP and Curcumin as Meriva Curcuma Phospholipid Complex powder

The bread will be manufactured and packaged by a bread manufacturing company.

Participants will be instructed on how to consume the bread (as part of their habitual diet) at their initial baseline visit to the research clinic. The bread is to be consumed as two slices together in the one meal, preferably at breakfast time each day.

To assess compliance:
1. Participants will be asked to record their daily consumption of bread in a standardised log provided to them.
2. Participants will be asked to return all bread bags/packets as well as any remaining or uneaten bread slices.
Intervention code [1] 313004 0
Treatment: Other
Intervention code [2] 313005 0
Prevention
Comparator / control treatment
Phytosterol placebo - canola oil
Curcumin placebo powder - lucarotin 1 CWD/Y and apo carotenal 2%
Control group
Placebo

Outcomes
Primary outcome [1] 308222 0
Total cholesterol concentration in blood plasma
Timepoint [1] 308222 0
At baseline (week zero) and at week 4 (end of study)
Primary outcome [2] 308223 0
Low-density lipoprotein cholesterol concentration in blood plasma
Timepoint [2] 308223 0
At baseline (week zero) and at week 4 (end of study)
Secondary outcome [1] 354270 0
Composite secondary outcome: Lipoprotein profile (particle size, particle concentration, particle subclass distribution).
Timepoint [1] 354270 0
At baseline (week zero) and at week 4 (end of study)
Secondary outcome [2] 354271 0
Composite secondary outcome: Plasma Inflammatory mediators (i.e. CRP, fibrinogen, IL-6, IL-1beta, IkB, iCAM) will be measured by ELISA analysis.
Timepoint [2] 354271 0
At baseline (week zero) and week 4 (end of study)
Secondary outcome [3] 354272 0
Cardiovascular Disease Risk - using the Framingham cardiovascular disease risk algorithm.
Timepoint [3] 354272 0
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
Gender
Both males and females
Can healthy volunteers participate?
No
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 e.g. gluten, wheat
* 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.

Breads were colour-coded by kwik locks on packaging by the manufacturer so as to maintain double-blinding (lead investigators and participants)

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
Not Applicable
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
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
Recruitment postcode(s) [1] 24894 0
2308 - Newcastle University

Funding & Sponsors
Funding source category [1] 301269 0
University
Name [1] 301269 0
University of Newcastle
Address [1] 301269 0
University Drive
Callaghan
NSW 2308
Country [1] 301269 0
Australia
Funding source category [2] 301271 0
Commercial sector/Industry
Name [2] 301271 0
Newtrition Asia Research Grant Program
Address [2] 301271 0
BASF South East Asia Pte Ltd.
7 Tamasek Boulevard, 038987 Singapore, Singapore
Country [2] 301271 0
Singapore
Primary sponsor type
University
Name
University of Newcastle
Address
University of Newcastle
University Drive, Callaghan 2308 NSW
Country
Australia
Secondary sponsor category [1] 300911 0
None
Name [1] 300911 0
Address [1] 300911 0
Country [1] 300911 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302012 0
The University of Newcastle Human Research Ethics Committee
Ethics committee address [1] 302012 0
The Chancellery
The University of Newcastle
University Drive
Callaghan NSW 2308
Ethics committee country [1] 302012 0
Australia
Date submitted for ethics approval [1] 302012 0
07/12/2017
Approval date [1] 302012 0
22/01/2018
Ethics approval number [1] 302012 0
H-2015-0162

Summary
Brief summary
The study aims to reduce circulating blood lipids (fats) and inflammation, two key modifiable risk factors of dyslipidaemia; a major contributor to heart disease. Plant sterols and curcumin are potent cholesterol-lowering and anti-inflammatory agents, respectively. We have previously investigated this novel combination as dietary supplements and now pose the development of a functional food containing both ingredients. We hypothesis that the functional food containing plant sterols and curcumin will be an effective delivery mode for both bioactives, have enhanced compliance and be effective for lowering circulating blood lipids and inflammatory markers in individuals with high cholesterol.
Trial website
N/A
Trial related presentations / publications
N/A
Public notes
N/A

Contacts
Principal investigator
Name 88850 0
Prof Manohar Garg
Address 88850 0
Nutraceuticals Research Program
305C Medical Science Building
University of Newcastle
University Drive
Callaghan, NSW 2308
Country 88850 0
Australia
Phone 88850 0
+61-2-4921 5647
Fax 88850 0
+61-2-4921 2028
Email 88850 0
manohar.garg@newcastle.edu.au
Contact person for public queries
Name 88851 0
Prof Manohar Garg
Address 88851 0
Nutraceuticals Research Program
305C Medical Science Building
University of Newcastle
University Drive
Callaghan, NSW 2308
Country 88851 0
Australia
Phone 88851 0
+61-2-4921 5647
Fax 88851 0
+61-2-4921 2028
Email 88851 0
manohar.garg@newcastle.edu.au
Contact person for scientific queries
Name 88852 0
Prof Manohar Garg
Address 88852 0
Nutraceuticals Research Program
305C Medical Science Building
University of Newcastle
University Drive
Callaghan, NSW 2308
Country 88852 0
Australia
Phone 88852 0
+61-2-4921 5647
Fax 88852 0
+61-2-4921 2028
Email 88852 0
manohar.garg@newcastle.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents 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