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Trial registered on ANZCTR

Registration number

ACTRN12617000302358

Ethics application status

Approved

Date submitted

23/02/2017

Date registered

27/02/2017

Date last updated

8/03/2018

Type of registration

Prospectively registered

Titles & IDs

Public title

Short-term effects of black tea on vascular function in healthy adults

Scientific title

Short-term effects of black tea on vascular function in healthy adults

Secondary ID [1]

None

Universal Trial Number (UTN)

U1111-1193-4680

Trial acronym

Linked study record

Health condition

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

endothelial function

high blood pressure

Condition category

Condition code

Cardiovascular

Normal development and function of the cardiovascular system

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

15 healthy men and women 18 to 75 years old will be recruited from the general population. Volunteers will have no history of major chronic disease.
A randomised, controlled, cross-over designed trial will be performed.
Each participant will complete 3 visits in random order. Prior to each visit participants will be asked to consume a standard meal for dinner (the night before their visit) and a low-fat breakfast (on the morning of their visit). Prior to the first visit, participants will be asked to document the meals so that they are able to repeat them for subsequent visits. For each visit participants will attend the School of Medicine and Pharmacology Research Unit at Royal Perth Hospital in the morning 2.5 hours after breakfast.
Participants will consume for 28 days, 3 cups per day (morning, during the day and afternoon/evening), of the following beverages:
1. Hot water (200 ml)
2. Black tea (2 g tea leaves infused in 200 ml)
3. Black tea with added milk (2 g tea leaves infused in 200 ml plus 20 ml of low fat [1.5%] milk)
The order of beverage consumption will be randomly assigned. There will be no washout between periods.
On the morning of each visit, participants consume 1 cup of their assigned beverage with their breakfast meal, then a second cup 1.5 hours later. One hour after this they will attend the clinic for assessments of outcomes.
All teas will be matched for total polyphenol content.
Adherence will be monitored using participant diaries, tea bag counts and measurement of biomarkers of tea-derived flavonoid exposure in urine.

Intervention code [1]

Lifestyle

Comparator / control treatment

Participants will consume for 28 days, 3 cups per day (morning, during the day and afternoon/evening), of the following beverages:
1. Hot water (200 ml)
2. Black tea (2 g tea leaves infused in 200 ml)
3. Black tea with added milk (2 g tea leaves infused in 200 ml plus 20 ml of low fat [1.5%] milk)
The order of beverage consumption will be randomly assigned.

Control group

Active

Outcomes

Primary outcome [1]

Primary outcome: endothelial function (flow-mediated dilation)
Flow-mediated dilation (FMD) of the brachial artery will be measured non-invasively using ultrasound. This measurement will be performed 1.5-2.0 hours after the last beverage, and again 3.0-3.5 hours after the last beverage.
A trained ultrasonographer dedicated to the research protocol and blinded to the interventions used will perform all measurements according to a published protocol. Briefly, subjects are studied in a quiet, temperature-controlled room (21 to 25 degrees Celcius) while resting in a supine position. Participants rest for 15 minutes in the supine position before initiation of FMD measurement. The left arm is extended and supported comfortably on a foam mat. ECG is monitored continuously. For the ultrasound, a 12-MHz transducer connected to an Acuson Aspen 128 ultrasound device (Acuson Corp.) is fixed in position with a clamp over the brachial artery 5 to 10 cm proximal to the antecubital crease. After a baseline artery diameter recording of 1 min, a blood pressure cuff is placed around the left forearm and inflated to 200 mm Hg. The cuff is released after 5 min, inducing reactive hyperemia. The brachial artery image is then recorded for 4 min (240 seconds) after cuff deflation to assess flow-mediated dilatation. Images are downloaded for retrospective analysis. Analysis of FMD of the brachial artery is performed with semi-automated edge detection software, which automatically calculates the brachial artery diameter, corresponding to the internal diameter. This is gated to the R wave of ECG, with measurements taken at end diastole. Responses are calculated as the percentage change in brachial artery diameter from baseline. The FMD is measured at 10 second intervals to 240 seconds after cuff deflation.
The primary outcome measure is the mean FMD between 60 seconds and 240 seconds. Analysis will also be performed using peak FMD as a secondary outcome.

Timepoint [1]

1.5-2.0 hours after the last beverage, and again 3.0-3.5 hours after the last beverage, at the end of each intervention period (on day 28 of each period).

Secondary outcome [1]

Secondary outcome: home blood pressure
Participants will monitor their home blood pressure in the morning, afternoon and evening each day for the last 7 days of each of the 3 intervention periods. During each 7-day home blood pressure measurement period, participants measure their blood pressure: (i) in the morning ~30 minutes after waking and prior to breakfast; (ii) in the afternoon between lunch and dinner; and (iii) in the evening ~1-2 hour after dinner. Blood pressures will be measured using an A&D Medical UA-67PC digital blood pressure monitor (A&D Instruments Ltd.). After a 5-min rest in a seated position, 5 blood pressure measurements are performed with a 1-min interval between measurements. The first reading is discarded.

Timepoint [1]

Participants will monitor their home blood pressure in the morning, afternoon and evening each day for the last 7 days of each of the 3 intervention periods.

Secondary outcome [2]

Secondary outcome: office blood pressure

Timepoint [2]

Office blood pressure will be measured, following a 5 minute rest in the seated position, 5 times at 1 minute intervals, from 1 hour after the last beverage, and then each hour for 4 hours. This will be performed at the end of each 28 day intervention period (day 28).

Secondary outcome [3]

Secondary outcome: arterial stiffness
Arterial stiffness will be assessed non-invasively using the SphygomCor pulse wave analysis system. Measurements of pulse wave velocity, central blood pressure and augmentation index will be performed at 2.0-2.5 hours after the last beverage (5 replicates). The carotid–femoral pulse wave velocity is measured after 5 min rest in a supine position by applanation tonometry using the Sphygmo- Cor pulse wave analysis system (AtCor Medical, Sydney, Australia. Model MM3. Software version 9). Before measuring pulse wave velocity, systolic and diastolic blood pressure, measured using the Dinamap PRO 100 oscillometric recorder, are entered. The ECG is recorded throughout the procedure. Pulse waves are recorded at the carotid and then femoral locations. The pulse wave velocity is calculated from measurements of pulse transit time and distance travelled by the pulse wave. The augmentation index is measured from the peripheral pulse pressure curve registered at the radial artery.

Timepoint [3]

Measurements of pulse wave velocity, central blood pressure and augmentation index will be performed at 2.0-2.5 hours after the last beverage (5 replicates). Performed at the at the end of each intervention period (day 28).

Secondary outcome [4]

Secondary outcome: faecal microflora
Faecal samples will be used to measure faecal microflora and will be frozen until later analysis.

Timepoint [4]

Participants will collect a faecal sample at the end of each 28 day period period.

Secondary outcome [5]

Secondary outcome: office heart rate

Timepoint [5]

Office heart rate will be measured, following a 5 minute rest in the seated position, 5 times at 1 minute intervals, from 1 hour after the last beverage, and then each hour for 4 hours. Performed at the end of each 28 day intervention period.

Secondary outcome [6]

Secondary outcome: home heart rate
Participants will monitor their home heart rate in the morning, afternoon and evening each day for the last 7 days of each of the 3 intervention periods. During each 7-day home hear rate measurement period, participants measure their heart rate: (i) in the morning ~30 minutes after waking and prior to breakfast; (ii) in the afternoon between lunch and dinner; and (iii) in the evening ~1-2 hour after dinner. Heart rate will be measured using an A&D Medical UA-67PC digital blood pressure monitor (A&D Instruments Ltd.). After a 5-min rest in a seated position, 5 heart rate measurements are performed with a 1-min interval between measurements. The first reading is discarded.

Timepoint [6]

Participants will monitor their heart rate in the morning, afternoon and evening each day for the last 7 days of each of the 3 intervention periods.

Eligibility

Key inclusion criteria

men and women
Aged 18 to 75 years old
No history of major chronic disease.

Minimum age

18 Years

Maximum age

75 Years

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key exclusion criteria

1 current or recent (<12 months) smoking
2 body mass index < 18 or > 35 kg/m2,
3 history of cardiovascular or peripheral vascular disease,
4 diagnosed diabetes, and non-diabetic individuals with fasting plasma glucose concentrations greater than or equal to 6.5 mmol/L,
5 a psychiatric illness, or other major illnesses such as cancer,
6 current or recent (within previous 6 months) significant weight loss or gain (> 6% of body weight),
7 alcohol intake > 210 g per wk for women and > 280 g per wk for men,
8 inability or unwillingness to follow the study protocol.

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)

Allocation is not concealed

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

Simple randomisation using a randomisation table created by computer software

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

The sample size of 15 participants completing the trial has been calculated on the primary endpoint of plasma FMD. With alpha=0.01, 15 participants will provide >90% power to detect a 1% difference (a 10% difference in percentage terms) in the mean FMD between 60 and 240 seconds post ischaemia. This assumes a SD of 3% based on our previous studies, a correlation between post ischaemia measures of 0.6, a correlation between mean (60-240 second) FMD at 1.5-2.0 hours and 3.0-3.5 hours of 0.6, and a minimum of 18 FMD measures at 1.5-2.0 hours and 3.0-3.5 hours. A 1% difference in flow-mediated dilatation is substantial and clinically important.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

15/03/2017

Actual

2/03/2017

Date of last participant enrolment

Anticipated

3/07/2017

Actual

31/03/2017

Date of last data collection

Anticipated

29/09/2017

Actual

27/09/2017

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Funding & Sponsors

Funding source category [1]

University

Name [1]

University of Western Australia

Address [1]

Level 4
Medical Research Foundation Building
Rear 50 Murray Street
Perth, WA 6000

Country [1]

Australia

Primary sponsor type

Individual

Name

Jonathan Hodgson

Address

Level 4
Medical Research Foundation Building
Rear 50 Murray Street
Perth, WA 6000

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

University of Western Australia Human Ethics Committee

Ethics committee address [1]

The University of Western Australia
35 Stirling Highway
Crawley WA 6009

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

12/08/2016

Approval date [1]

15/09/2016

Ethics approval number [1]

RA/4/1/8566

Summary

Brief summary

Population studies indicate that regular consumption of tea can reduce the risk of cardiovascular disease by between 5 and 15%. The pooled estimate of risk reduction for black tea is influenced by two studies which included populations from the United Kingdom where milk is traditionally added to tea. This has led to the suggestion that addition of milk may diminish or negate cardiovascular health benefits of tea.
Results of population and intervention studies suggest that regular consumption of tea can reduce blood pressure by 1 to 10 mm Hg. At a population level, a 5 mm Hg lower blood pressure would be associated with a 10% lower risk of coronary artery disease, and a 20% lower risk of stroke.
A meta-analysis of randomised controlled trials to have assessed the effects of tea on endothelial function was recently published. This analysis suggests that acute and chronic tea ingestion can improve endothelial function, assessed by measuring flow-mediated dilatation of the brachial artery, by 30 to 40% (~2% absolute improvement). If sustained, this would be associated with about a 25% reduction in risk of cardiovascular events, which would be consistent with estimates of risk reduction from population studies.
The precise pathway linking flavonoids to vascular function is not clear. However, it is known that the majority of dietary flavonoids are not absorbed or bioactive without prior metabolism by specific groups of enzymes produced by the microbes residing in the gastrointestinal tract (the microbiome). Although increased flavonoid intake can improve measures of vascular function, there is substantial inter-individual variability in response. Current knowledge of flavonoid metabolism indicates that this is largely due to individual differences in the capacity of the microbiome to metabolise flavonoids. However, this hypothesis has yet to be explored. Initial research needs to describe changes to the microbiome that occur with tea consumption.
Furthermore, despite studies showing that the effect of the addition of milk to tea on bioavailability of tea flavonoids is modest, questions remain regarding the effects of milk to black tea on its bioactivity. One study has suggested that addition of milk almost negates the acute improvement in endothelial function. However, it is possible that this may relate to the study design, where endothelial function was assessed at a single time point following a single dose of tea. It is possible that addition of milk may delay absorption of the active components of tea (the flavonoids), but the overall impact on endothelial function is similar.
Thus, the primary aim of the proposed study will be to investigate the short-term effects of black tea on endothelial function. We will investigate the effect of the addition of milk to black tea on its bioactivity. We will also describe and compare the changes to the microbiome after short-term regular consumption of black tea with and without milk.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Jonathan Hodgson

Address

Edith Cowan University
Level 4
Medical research Foundation Building
Rear 50 Murray Street
Perth, WA 6000

Country

Australia

Phone

+61 (0)8 92240267

Fax

Jonathan.Hodgson@ecu.edu.au

Contact person for public queries

Name

Jonathan Hodgson

Address

Edith Cowan University
Level 4
Medical research Foundation Building
Rear 50 Murray Street
Perth, WA 6000

Country

Australia

Phone

+61 (0)8 92240267

Fax

Jonathan.Hodgson@ecu.edu.au

Contact person for scientific queries

Name

Jonathan Hodgson

Address

Edith Cowan University
Level 4
Medical research Foundation Building
Rear 50 Murray Street
Perth, WA 6000

Country

Australia

Phone

+61 (0)8 92240267

Fax

Jonathan.Hodgson@ecu.edu.au

No information has been provided regarding IPD availability

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No Supporting Document Provided

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