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Trial registered on ANZCTR


Registration number
ACTRN12615000361505
Ethics application status
Approved
Date submitted
25/03/2015
Date registered
21/04/2015
Date last updated
24/03/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
The effects of acute and long-term apple consumption on risk factors for cardiovascular disease
Scientific title
The effects of acute and long-term apple consumption on risk factors for cardiovascular disease in individuals with at least one current risk factor.
Secondary ID [1] 286412 0
None
Universal Trial Number (UTN)
U1111-1168-7209
Trial acronym
HHBA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cardiovascular Disease 294572 0
Gut Microbiome 294573 0
Condition category
Condition code
Cardiovascular 294876 294876 0 0
Diseases of the vasculature and circulation including the lymphatic system
Cardiovascular 294877 294877 0 0
Hypertension
Oral and Gastrointestinal 294878 294878 0 0
Normal oral and gastrointestinal development and function

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Acute component of study: 1 whole apple (medium size) + 1 apple skin blended with 1/2 cup water.
Measurements will be taken before (baseline) and 2 hours after ingestion of the treatment.


Long-term component of study: 1 whole apple (medium size) + 1 apple skin blended with 1/2 cup water twice a day for 4 weeks.
Volunteers will be asked to only use 'Pink Lady' apples.

Volunteers will be asked to fill in a diary and we will also be measuring urinary metabolites to monitor adherence to the intervention.

Measurements will be taken on day 1 (baseline) and day 28.

The washout period will be two weeks prior to commencing the study and for two weeks inbetween treatment periods. During these times and throughout the study we will ask volunteers to reduce their flavonoid intake:
- Limit tea to 1 or less cups per day
- Limit coffee to 2 or less cups per day
- Limit dark chocolate
- Limit red wine
- Reduced onion intake
- Do not eat any other apples
- Avoid eating large quantities of curly kale, leeks, broccoli, capers and blueberries.
Intervention code [1] 291484 0
Treatment: Other
Comparator / control treatment
Acute component of study: 1 apple (medium size) without skin blended with 1/2 cup water. Measurements will be taken before (baseline) and 2 hours after ingestion of the treatment.
chronic component of study: 1 apple (medium size) without skin blended with 1/2 cup water twice a day for 4 weeks.
Volunteers will be asked to only use 'Pink Lady' apples.

Measurements will be taken on day 1 (baseline) and day 28.
Control group
Dose comparison

Outcomes
Primary outcome [1] 294630 0
Primary outcome: % Flow-mediated dilatation of the brachial artery assesed by ultrasonogaphy.
Timepoint [1] 294630 0
Timepoint for chronic intervention: Baseline and 4 weeks after intervention commencement
Timepoint for acute intervention: Baseline and 2 hours after intervention
Secondary outcome [1] 313759 0
Blood pressure assessed using the V100 Dinamap
Timepoint [1] 313759 0
Timepoint for chronic intervention: Baseline and 4 weeks after intervention commencement
Timepoint for acute intervention: Baseline and 2 hours after intervention
Secondary outcome [2] 313760 0
Arterial stiffness measured as pulse wave velocity and augmentation index using the SphygomoCor XCEL device.
Timepoint [2] 313760 0
Timepoint for chronic intervention: Baseline and 4 weeks after intervention commencement
Timepoint for acute intervention: Baseline and 2 hours after intervention
Secondary outcome [3] 313761 0
Blood pressure during stess assessed by monitoring blood pressure during a cognitive demand battery test.
Timepoint [3] 313761 0
Timepoint for chronic intervention: Baseline and 4 weeks after intervention commencement
Timepoint for acute intervention: Baseline and 2 hours after intervention
Secondary outcome [4] 313762 0
Plasma quercetin metabolites assessed by liquid chromatography mass spectromemetry
Timepoint [4] 313762 0
Timepoint for chronic intervention: Baseline and 4 weeks after intervention commencement
Timepoint for acute intervention: Baseline and 2 hours after intervention
Secondary outcome [5] 313763 0
Plasma markers of nitric oxide status assessed by chemiluminescence methods
Timepoint [5] 313763 0
Timepoint for chronic intervention: Baseline and 4 weeks after intervention commencement
Timepoint for acute intervention: Baseline and 2 hours after intervention
Secondary outcome [6] 313764 0
Levels of plasma F2-isoprostanes assessed by gas chromatography mass spectrometry
Timepoint [6] 313764 0
Timepoint for chronic intervention: Baseline and 4 weeks after intervention commencement
Secondary outcome [7] 313765 0
Effect of the treatment on the gut microflora assessed by collecting faecal samples and measuring the differences in bacteria species
Timepoint [7] 313765 0
Timepoint for chronic intervention: Baseline and 4 weeks after intervention commencement

Eligibility
Key inclusion criteria
We are looking for volunteers with one or more of the following:
- Slightly elevated blood pressure (120 < systolic BP < 160)
- High blood sugar (5.6 < glucose < 6.5)
- High cholesterol (5 < total cholesterol < 8)
- Central obesity (men > 94cm; women > 80cm)
It is critical to the study that participants are not currently taking any blood pressure or cholesterol lowering medication.
Minimum age
20 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Current or recent (12 months) smoking
- Body mass index less than 18 or greater than 40 kg/m2
- History of cardiovascular or peripheral vascular disease
- A systolic blood pressure less than 100 or greater than 160 mmHg.
- A diastolic blood pressure less than 50 or greater than 100 mmHg
- Diagnosed diabetes, and non-diabetic individuals with fasting plasma glucose concentrations greater than 6.5 mmol/L
- A psychiatric illness
- Other major illnesses such as cancer
- Current or recent (within previous 6 months) significant weight loss or gain ( greater than 6% of body weight) or actively trying to lose weight
- Alcohol intake greater than 210g per week for women and greater than 280 g per week for men
- Women who are lactating, pregnant or wishing to become pregnant during the study

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Eligible participants will be randomly assigned to one of 2 sequence. 30 sealed opaque envelopes, numbered 1-30, each containing one of the 2 sequence orders for intervention diets will be used for randomisation by opening an envelope, in consecutive order, as participants are entered into the study. The computer generated random numbers and sealed opaque envelopes will be completed and held by a person independent of study researchers within the University of Western Australia. The study coordinator will contact the person independent of study researchers to obtain the next available envelope once an individual is deemed eligible. The envelope will be opened and the code will be recorded
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Using the Mersenne Twister pseudorandom number generator
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Statistical analyses will be performed according to a pre-specified statistical analysis plan using IBM SPSS Statistics Version 21 (2012, Armonk, NY: IBM Corp.); SAS software (Version 9.3: SAS Institute Inc); or STATA 12 (StataCorp). The primary analysis will be modified intention to treat (all randomised participants for which we have collected baseline data). Analysis will be performed using mixed models (including all available data). The sample size for this study has been calculated on the primary endpoint of blood vessel function, measured as flow mediated dilation of the brachial artery (FMD). 30 participants will provide more than 80% power to detect a difference between apple flavonoid treatment and control (placebo) treatment. This has been based on a difference of 1.5% FMD and a standard deviation of 2%. We have previously demonstrated in a group of 30 subjects a significant increase in FMD following acute treatment with quercetin-rich apples.

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)
WA
Recruitment hospital [1] 3607 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 9396 0
6000 - Perth

Funding & Sponsors
Funding source category [1] 290985 0
Government body
Name [1] 290985 0
National Health and Medical Research Council
Address [1] 290985 0
GPO Box 1421
Canberra ACT 2601
Country [1] 290985 0
Australia
Primary sponsor type
University
Name
The University of Western Australia
Address
35 Stirling Highway
Crawley WA 6009
Country
Australia
Secondary sponsor category [1] 289665 0
None
Name [1] 289665 0
Address [1] 289665 0
Country [1] 289665 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292574 0
The University of Western Australia Human Research Ethics Committee
Ethics committee address [1] 292574 0
35 Stirling Highway
Crawley WA 6009
Ethics committee country [1] 292574 0
Australia
Date submitted for ethics approval [1] 292574 0
Approval date [1] 292574 0
23/01/2015
Ethics approval number [1] 292574 0
RA/4/1/5880

Summary
Brief summary
This project aims to determine if a major flavonoid component found in apple skin can improve blood vessel function and blood pressure in human volunteers. The apple variety Cripps Pink, marketed as ‘Pink Lady’ is particularly rich in the flavonoid quercetin. Our previous short term studies with pure quercetin and apples show improved blood vessel function. We now wish to determine if long term consumption (4 weeks) of apples will improve vessel function and lower blood pressure and try to understand the biochemical mechanism of this beneficial effect.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 56034 0
Prof Kevin D. Croft
Address 56034 0
The University of Western Australia School of Medicine and Pharmacology
Rear 50 Murray St, Perth WA 6000
Country 56034 0
Australia
Phone 56034 0
+61 8 9224 0275
Fax 56034 0
Email 56034 0
kevin.croft@uwa.edu.au
Contact person for public queries
Name 56035 0
Miss Nicola Bondonno
Address 56035 0
The University of Western Australia School of Medicine and Pharmacology
Rear 50 Murray St, Perth WA 6000
Country 56035 0
Australia
Phone 56035 0
+61 8 9224 0342
Fax 56035 0
Email 56035 0
nicola.bondonno@uwa.edu.au
Contact person for scientific queries
Name 56036 0
Miss Nicola Bondonno
Address 56036 0
The University of Western Australia School of Medicine and Pharmacology
Rear 50 Murray St, Perth WA 6000
Country 56036 0
Australia
Phone 56036 0
+61 8 9224 0342
Fax 56036 0
Email 56036 0
nicola.bondonno@uwa.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