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Trial registered on ANZCTR


Registration number
ACTRN12618001455257
Ethics application status
Approved
Date submitted
21/08/2018
Date registered
29/08/2018
Date last updated
29/08/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Plant Sterols and Beta-Glucan for Reducing Cardiovascular Disease Risk (Beta-GAPS Trial)
Scientific title
ß-Glucan and Phytosterols for Lipid-Lowering in Hypercholesterolaemic Individuals: A Randomised Controlled Trial (ß-GAPS Trial)
Secondary ID [1] 292633 0
None
Universal Trial Number (UTN)
Trial acronym
ß-GAPS Trial
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
Hypercholesterolaemia 304356 0
Inflammation 304357 0
Cardiovascular Disease Risk 304358 0
Condition category
Condition code
Cardiovascular 303693 303693 0 0
Other cardiovascular diseases
Diet and Nutrition 303694 303694 0 0
Other diet and nutrition disorders
Inflammatory and Immune System 303695 303695 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The effects of dietary supplementation with 2g of phytosterols (phytosterol-enriched margarine) with or without 3g oat beta-glucan each day. This randomised control trial is a 2x2 factorial placebo-controlled, double-blinded design.
Hypercholesterolaemic individuals will be randomly assigned to one of the following treatment arms for 6 weeks:
Arm 1: Placebo-Placebo (PP) Group: 8 small sweet vanilla wholemeal biscuits (no phytosterols, no ß-glucan) per day.
Arm 2: ß-Glucan (ßG) Group: 8 sweet vanilla wholemeal biscuits fortified with oat ß-glucan powder (no phytosterols, 3g oat ß-glucan) per day.
Arm 3: Phytosterol (PS) Group: 8 sweet vanilla wholemeal biscuits fortified with Logical margarine (2g phytosterols, no ß-glucan) per day.
Arm 4: Phytosterol-ß-Glucan Group (ßG-PS) : 8 sweet vanilla wholemeal biscuits fortified with ß-glucan and Logicol margarine (2g phytosterols, 3g oat ß-glucan) per day.

Prior to the trial appointments, participants complete consent form and questionnaires (medical, physical and 3-day food diary) as fast overnight (10hours) avoiding vigorous activity and alcohol 24hours prior.
Participants will attend two clinic visits (baseline and post-intervention) at the Nutraceuticals Research Program at the University of Newcastle that will take 30 minutes in which anthropometric, blood pressure, questionnaires and fasted blood sample will be collected by the lead investigator (PhD student and Accredited Practising Dietitian). Participants will be given the option to participate in an optional 2-hour blood glucose test meal component which is only at baseline, following straight after the appointment. This component involves 5 finger prick tests at timepoint 0, 30min, 60min, 90min and 120min.

The biscuits will be made prior to the study and packaged/sealed and provided to participants along with instructions on how to consume the biscuits at their initial visit to the research clinic. The biscuits are to be consumed by participants in between meals (i.e. snack times) with fluid and a daily biscuit consumption log kept for the duration of the trial.

To assess compliance:
1. Participants will be asked to record their daily consumption of the intervention biscuits in a standardised log provided to them.
2. Participants will be asked to return all unused biscuit bags to the study site when they attend their final appointment at the end of the study period. They will be asked to keep any unfinished and empty biscuits and return them at the end of the study.
Intervention code [1] 298866 0
Treatment: Other
Intervention code [2] 298867 0
Prevention
Comparator / control treatment
Phytosterol placebo - low-fat, canola-based margarine (commercially available) will be used in the biscuits in place of the phytosterol-enriched canola-based margarine (commercially available).
Beta-glucan placebo - wholemeal plain flour (commercially available)
Control group
Placebo

Outcomes
Primary outcome [1] 303056 0
Change in fasting plasma total cholesterol concentration
Timepoint [1] 303056 0
Baseline (day 1) and week 6 (end of study)
Primary outcome [2] 303057 0
Change in fasting Low-density lipoprotein cholesterol concentration in blood plasma
Timepoint [2] 303057 0
Baseline (day 1) and at week 6 (end of study)
Secondary outcome [1] 337792 0
Composite secondary outcome: change in Inflammatory mediators (i.e. CRP, IL-6, TnF-alpha, IL-1beta, ICAM) using Elisa method
Timepoint [1] 337792 0
At baseline (day 1) and week 6 (end of study)
Secondary outcome [2] 337793 0
AUC postprandial glucose Sanofi BGSTAR glucose meter (glucose).
Timepoint [2] 337793 0
Baseline only (day 1) at five time points: 0min, 30min, 60min, 90min and 120min.
Secondary outcome [3] 350929 0
Cardiovascular Disease Risk - using the Framingham cardiovascular disease risk algorithm.
Timepoint [3] 350929 0
At baseline (week zero) and week 6 (end of study)

Eligibility
Key inclusion criteria
* Age: 18-70 years
* Gender: both males and females
* Fasting Total cholesterol levels greater than or equal to 5.5mmol/L
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 and/or oat beta-glucan 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
* 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 (block size 8) method to ensure gender-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 administering 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.

All the data relating the significant effects of phytosterols and/or oat beta-glucan will be expressed as mean±SEM. Normality will be assessed using Shapiro Wilk's Test and visual plots e.g. histograms, box and scatter plots. Changes from baseline will be assessed using paired samples t-tests for parametric data and Wilcoxon Signed Rank Test for non-parametric data. The effect of interventions on blood lipids and secondary outcome markers between groups will be estimated using one-way ANOVA for parametric data or Kruskall Wallis for non-parametric data. Two-way ANOVA will be used to investigate whether there will be a significant main effect for each independent variable and an interaction term will be used to evaluate the complementary and/or synergistic effects between phytosterols and oat ß-glucan. Tukey’s honestly significant difference will be used for all post-hoc comparisons. A significance of P<0.05 will indicate statistically significant results. Baseline measures will be used as covariates to assess for any potential confounders using logistic regression.

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] 16911 0
2308 - Newcastle University

Funding & Sponsors
Funding source category [1] 297272 0
Self funded/Unfunded
Name [1] 297272 0
N/A
Address [1] 297272 0
N/A
Country [1] 297272 0
Primary sponsor type
University
Name
University of Newcastle
Address
University Drive
Callaghan, NSW
2308
Country
Australia
Secondary sponsor category [1] 296245 0
None
Name [1] 296245 0
N/A
Address [1] 296245 0
N/A
Country [1] 296245 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298388 0
University of Newcastle Human Research Ethics Committee
Ethics committee address [1] 298388 0
The Chancellery The University of Newcastle University Drive Callaghan NSW 2308
Ethics committee country [1] 298388 0
Australia
Date submitted for ethics approval [1] 298388 0
31/03/2017
Approval date [1] 298388 0
21/07/2017
Ethics approval number [1] 298388 0
H-2017-0091

Summary
Brief summary
Cardiovascular disease (CVD) is the leading cause of death worldwide. Dyslipidaemias and insulin resistance have been associated with the development of CVD. In addition, elevated levels of chronic inflammation has also been shown to play a key role in the pathobiology of CVD. Targeting blood lipid levels, insulin sensitivity and chronic inflammation in high risk individuals may help to ameliorate these modifiable risk factors and reduce the overall risk of developing CVD.

Phytosterols are well-known cholesterol-lowering agents, resulting in 10% reductions in LDL-C in only 3-4 weeks of supplementation. Oat beta-glucan is a rich source of soluble fibre which has been shown to lower cholesterol levels with implications for glucose control. This project aims to investigate if combined dietary supplementation with plant sterols and beta-glucan reduces blood cholesterol and to a larger extent than either of the treatments alone.It is expected that participants will have improved levels of blood cholesterol as well as an overall reduced 10-year risk of developing CVD.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 59694 0
Prof Manohar Garg
Address 59694 0
Nutraceuticals Research Program
305C Medical Science Building University of Newcastle University Drive Callaghan, NSW 2308
Country 59694 0
Australia
Phone 59694 0
+61-2-4921 5647
Fax 59694 0
+61-2-4921 2028
Email 59694 0
manohar.garg@newcastle.edu.au
Contact person for public queries
Name 59695 0
Prof Manohar Garg
Address 59695 0
Nutraceuticals Research Program 305C Medical Science Building University of Newcastle University Drive Callaghan, NSW 2308
Country 59695 0
Australia
Phone 59695 0
+61-2-4921 5647
Fax 59695 0
+61-2-4921 2028
Email 59695 0
manohar.garg@newcastle.edu.au
Contact person for scientific queries
Name 59696 0
Prof Manohar Garg
Address 59696 0
Nutraceuticals Research Program 305C Medical Science Building University of Newcastle University Drive Callaghan, NSW 2308
Country 59696 0
Australia
Phone 59696 0
+61-2-4921 5647
Fax 59696 0
+61-2-4921 2028
Email 59696 0
manohar.garg@newcastle.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary