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Trial registered on ANZCTR


Registration number
ACTRN12618000692235
Ethics application status
Approved
Date submitted
19/04/2018
Date registered
27/04/2018
Date last updated
9/04/2019
Date data sharing statement initially provided
9/04/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Statins & nutraceuticals to prevent cardiovascular ageing
Scientific title
Strategies to prevent cardiovascular aging in people at moderate risk of cardiovascular disease.
Secondary ID [1] 294654 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cardiovascular disease 307500 0
Condition category
Condition code
Cardiovascular 306584 306584 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Double-blind, randomized placebo-controlled trial with 4 treatment arms, run in parallel. Participants are randomised to one treatment arm where they receive all treatments listed in that treatment arm.
Arm 1: Atorvastatin 40mg, given as oral tablets once daily for 12 weeks + placebo given as oral tablets once daily for 12 weeks
Arm 2: Nutraceutical combination containing 500mg Berberine (berberine hydrochloride) + 200mg Red Yeast Rice Extract (equivalent to 3 mg Monacolin K) + 2g Plant Sterols + 1.2 billion CFU ENLIVA (Lactobacillus plantarum) given as oral tablets once daily for 12 weeks + placebo given as oral tablets once daily for 12 weeks
Arm 3: Atorvastatin 40mg, given as oral tablets once daily for 12 weeks + Nutraceutical combination containing 500mg Berberine (berberine hydrochloride) + 200mg Red Yeast Rice Extract (equivalent to 3 mg Monacolin K) + 2g Plant Sterols + 1.2 billion CFU ENLIVA (Lactobacillus plantarum) given as oral tablets once daily for 12 weeks
Arm 4: Statin placebo given as oral tablets once daily for 12 weeks + nutraceutical placebos given as oral tablets once daily for 12 weeks.

Compliance for all treatment arms will be monitored via tablet count from drug return.
Intervention code [1] 300950 0
Treatment: Drugs
Comparator / control treatment
Matching placebos will be provided for the active treatments (atorvastatin and nutraceutical combination), that are identical in size and appearance and be given as oral tablets. These will be comprised of Avicel (Microcrystalline cellulose).
Control group
Placebo

Outcomes
Primary outcome [1] 305578 0
Low density lipoprotein (LDL) cholesterol levels as assessed via fasting blood sample, taken after a 12 hour fast.
Timepoint [1] 305578 0
Baseline and at 12 weeks post intervention commencement.
Primary outcome [2] 305579 0
Vascular function as assessed via fasting ultrasound determination of flow-mediated dilation of the brachial artery, after a 12 hour fast.
Timepoint [2] 305579 0
Baseline and 12 weeks after intervention commencement.
Secondary outcome [1] 345813 0
Gut microbiome composition as assessed via plasma and stool levels of short chain fatty acids and bile acids.
Timepoint [1] 345813 0
Baseline and 12 weeks after intervention commencement.

Eligibility
Key inclusion criteria
Participants aged 50-70 years of age and who are at moderate risk of CVD will be recruited. Moderate risk will be defined as having one or more of the following:
1. Hypertension (mean clinic systolic > 135 mmHg, or diastolic > 85 mmHg, or treatment)
2. Dyslipidaemia (fasting total cholesterol > 5.5 mmol/L, or LDL > 2 mmol/L, or triglycerides > 1.5 mmol/L)
3. Central obesity (men > 100 cm and women > 89 cm)
4. Hyperglycaemia (fasting glucose > 5.5 mmol/L or treatment)
5. Overweight (BMI > 27)
6. A score of 10-15% as calculated by the Australian Absolute Cardiovascular Disease Risk Score calculator
Minimum age
50 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Previous known statin intolerance
• Current use of statin therapy
• Pregnant or lactating women
• BMI >35 kg/m2
• Any adult with a previous diagnosis of a severe co-existing medical condition that would prevent participation (e.g. severe dementia or terminal illness)
• Alcohol intake >3 standard drinks a day (men) or >2 standard drinks a day (women)
• Vegetarian, vegan or previous gastric banding surgery
• Current use of prebiotic or probiotic medications
• Recent use of antibiotics (<3 months)
• Current smoker or quit smoking within the last 3 months
• Unable to give informed consent

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)
Central randomization by computer generated numbers,
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomization using a randomization table created by computer software
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
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis
We are targeting a sample size of 130 men and women, with sample size calculations based on assumptions made on two primary outcomes (low-density lipoprotein (LDL) cholesterol levels and % change FMD). Two sample mean method with type I error of 5% and power of 80% was used in this calculation. According to data from the 2011 National Health Measurement Survey, the population mean LDL is 3.1 mmol/L, with a standard deviation (SD) of 0.7 mmol/L. We expect an average LDL difference of 0.4 mmol/L for patients who receive nutraceuticals or statin versus those who receive no nutraceutical or statin. A sample size of 100 is required for this endpoint. Therefore at least 25 participants in each study group is required to power the investigation of LDL. In terms of FMD, in order to detect a 2% difference between participants who receive nutraceuticals or statin versus those who receive no nutraceutical or statin, assuming an average FMD level of 6% with SD of 4%, a sample size of 126 is required, equating to 32 per group. These numbers will also provide sufficient power to detect changes in the main secondary endpoint, gut microbiome composition. Thirty-two participants per group will provide 80% power (type I error 5%) to detect a significant difference in bacterial profile (type II error 0.05) with an affect size of 70%.

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
A decision was made to stop the study before it started. This was predominantly due to updates in the literature regarding other studies. No participants were recruited and the study will no longer go ahead.
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)
WA

Funding & Sponsors
Funding source category [1] 299268 0
Government body
Name [1] 299268 0
NHMRC Program Grant
Address [1] 299268 0
National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601
Country [1] 299268 0
Australia
Primary sponsor type
University
Name
Curtin University
Address
Kent Street
Bentley WA 6102
Country
Australia
Secondary sponsor category [1] 298539 0
None
Name [1] 298539 0
N/A
Address [1] 298539 0
N/A
Country [1] 298539 0
Other collaborator category [1] 280072 0
University
Name [1] 280072 0
University of Western Australia
Address [1] 280072 0
35 Stirling Highway
Crawley WA 6009
Country [1] 280072 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300183 0
Curtin University Human Research Ethics Committee
Ethics committee address [1] 300183 0
Kent Street
Bentley WA 6102
Ethics committee country [1] 300183 0
Australia
Date submitted for ethics approval [1] 300183 0
Approval date [1] 300183 0
18/04/2018
Ethics approval number [1] 300183 0
HRE2018-0168

Summary
Brief summary

Cardiovascular disease (CVD) is the leading cause of death and disability. Ageing is associated with a number of traditional CVD risk factors, including high blood pressure and high cholesterol, as well as changes to the structure of our heart and blood vessels, which over time contribute to an increased risk of cardiovascular events. Statins are common cholesterol-lowering drugs that have been shown to reduce the risk of developing heart disease. Nutraceuticals are food components or active ingredients in food that may be used as therapeutic agents to help lower cholesterol and modify risk of heart disease. This project will investigate the effect of statins and nutraceuticals, either alone or in combination, on markers of heart and blood vessel function in people at moderate risk of heart disease. We hypothesise that statin therapy will delay the cardiovascular ageing process, as evidenced by improvements in structural and functional outcomes. These improvements will be further enhanced with adjunct nutraceutical therapy. In addition to the beneficial effects on risk factors for heart disease, nutraceutical compounds will offer additional benefit through changes to the gut microbiome, including improvements in bacterial diversity and composition, as well as alterations in the production of important short chain fatty acids and bile acids.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 82826 0
Dr Natalie Ward
Address 82826 0
School of Public Health
Curtin University
Kent Street
Bentley WA 6102
Country 82826 0
Australia
Phone 82826 0
+61 8 92664188
Fax 82826 0
Email 82826 0
natalie.ward@curtin.edu.au
Contact person for public queries
Name 82827 0
Dr Natalie Ward
Address 82827 0
School of Public Health
Curtin University
Kent Street
Bentley WA 6102
Country 82827 0
Australia
Phone 82827 0
+61 8 92664188
Fax 82827 0
Email 82827 0
natalie.ward@curtin.edu.au
Contact person for scientific queries
Name 82828 0
Dr Natalie Ward
Address 82828 0
School of Public Health
Curtin University
Kent Street
Bentley WA 6102
Country 82828 0
Australia
Phone 82828 0
+61 8 92664188
Fax 82828 0
Email 82828 0
natalie.ward@curtin.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
Study is no longer going ahead.
What supporting documents are/will be available?
No other documents available
Summary results
No Results