Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000629932p
Ethics application status
Submitted, not yet approved
Date submitted
8/04/2020
Date registered
29/05/2020
Date last updated
29/05/2020
Date data sharing statement initially provided
29/05/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
BOKA-T: Bioavailability Of Kawakawa Tea metabolites in human volunteers
Scientific title
BOKA-T: Bioavailability Of Kawakawa Tea metabolites in healthy male volunteers
Secondary ID [1] 300943 0
None
Universal Trial Number (UTN)
U1111-1248-8566
Trial acronym
BOKA-T
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metabolic disorders 316955 0
Condition category
Condition code
Metabolic and Endocrine 315149 315149 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will examine the response after an acute (single) ingestion of either water or different doses of Kawakawa tea (1g or 4g per 250ml of hot water). The postprandial state lasts for approximately 4-5 h post-meal period, the study is to be carried out for 6h. Participants under the supervision of clinical coordinator will complete a screening assessment and if eligible for entry into the trial will be required in fasted condition to consume either a kawakawa tea infusion (1g or 4g per 250ml of hot water) or only hot water within 15 minutes. Following the tea ingestion, a standard breakfast will be provided at 60 minutes. Blood will be sampled at 0, 30, 45, 60, 90, 120, 180, 240, 300 mins, and 24 h from an arm vein (total 220ml blood) by a certified phlebotomist or registered nurse. Urine samples will be collected for 24 h with a time frame of 0, 0-2, 2-4, 4-5, 5-24 h after the consumption of tea. A washout period of 1 week is required between each intervention, therefore the participants will be informed to come for their second and third intervention visits after a washout of 1 week.
Intervention code [1] 317262 0
Prevention
Comparator / control treatment
Hot water (250mL)
Control group
Placebo

Outcomes
Primary outcome [1] 323404 0
Composite primary outcome: To examine the bioavailability of Kawakawa and its metabolites following the consumption of tea infused with Kawakawa leaves
Timepoint [1] 323404 0
Fasting blood and urine samples will be collected.
After intervention- Blood samples will be collected at 30, 45, 60, 90, 120, 180, 240, 300 mins, and at 24 hours. Urine samples will be collected for 24 hours with a time frame of 0-2, 2-4, 4-5, 5-24 hours.
Untargeted Metabolomics will be utilised to analyse these samples
Secondary outcome [1] 381827 0
To measure kawakawa metabolites in plasma following consumption of different doses of Kawakawa infused Tea or hot water
Timepoint [1] 381827 0
Blood samples collected at fasting and then after the intervention at 30, 45, 60, 90, 120, 180, 240, 300 mins, and at 24 hours will be analysed for Kawakawa metabolites using both targeted as well as untargeted metabolic profiling approach.
Secondary outcome [2] 381828 0
To measure kawakawa metabolites in Urine collected for 24 hours after consumption of different doses of Kawakawa infused Tea or hot water.
Timepoint [2] 381828 0
Urine samples collected for 24 hours with a time frame of 0, 0-2, 2-4, 4-5, 5-24 hours will be analysed for Kawakawa metabolites using both targeted as well as untargeted metabolic profiling approach.
Secondary outcome [3] 381829 0
To measure the impact of Kawakawa tea ingestion on biochemical parameters of blood glucose level.
Timepoint [3] 381829 0
Plasma glucose will be measured using a Roche Cobas c311 autoanalyser by enzymatic colorimetric assay. Blood samples collected at 0, 30, 45, 60, 90, 120, 180, 240, 300 mins, and at 24 hours
Secondary outcome [4] 381830 0
To measure the impact of Kawakawa tea ingestion on biochemical parameters of blood insulin level.
Timepoint [4] 381830 0
Plasma insulin will be measured on a Roche Cobas e411 by electro-chemiluminescence immunoassay. Blood samples collected at 0, 30, 45, 60, 90, 120, 180, 240, 300 mins, and at 24 hours
Secondary outcome [5] 381831 0
To measure the impact of Kawakawa tea ingestion on biochemical parameters of blood lipids.
Timepoint [5] 381831 0
Fasting plasma lipids will be analysed by Roche Cobas c311 autoanalyser by enzymatic colorimetric assay. Blood samples collected at 0, 30, 45, 60, 90, 120, 180, 240, 300 mins, and at 24 hours

Eligibility
Key inclusion criteria
Males participants will be included to participate if
• BMI- 18-30 kg/m2
• Non-smokers
• Self-reported not consuming dietary supplements
• No medical conditions
Minimum age
18 Years
Maximum age
60 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
Participants will be excluded from participation if they:
• Female subjects
• Are taking dietary supplements or herbal remedies which may affect the study outcome
• Are allergic to pepper, nutmeg or similar spices
• Are diagnosed with gastrointestinal disease (i.e. celiac, Crohn’s, colitis, etc.) or pre-existing metabolic disease
• Are currently taking medications expected to interfere with normal digestive or metabolic processes including proton pump inhibitors, laxatives, etc.
• Have used antibiotics within the previous one month or were on long-term antibiotic therapy.

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)
Participants will be randomised to receive the intervention or the control as the first in a crossover sequence using computer-generated sequences.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Allocation sequence will be set up as through a web-based secure database. Sequences will not be accessible to the research team prior to allocation.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Randomised, Open-label, Three-arm, Three-period crossover trial
Phase
Not Applicable
Type of endpoint/s
Bio-availability
Statistical methods / analysis
Differences in the primary endpoints will be compared between treatment groups using Repeated measure ANOVA or non-parametric tests where appropriate and followed-up with posthoc tests. The relationship between secondary end-points will be assessed using multiple regression analysis.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/06/2020
Actual
Date of last participant enrolment
Anticipated
30/07/2020
Actual
Date of last data collection
Anticipated
30/09/2020
Actual
Sample size
Target
6
Accrual to date
Final
Recruitment outside Australia
Country [1] 22472 0
New Zealand
State/province [1] 22472 0
Auckland

Funding & Sponsors
Funding source category [1] 305385 0
University
Name [1] 305385 0
Liggins Institute, The University of Auckland
Country [1] 305385 0
New Zealand
Primary sponsor type
University
Name
Liggins Institute, The University of Auckland
Address
85 Park road, Grafton, Auckland 1023.
Country
New Zealand
Secondary sponsor category [1] 305800 0
None
Name [1] 305800 0
Address [1] 305800 0
Country [1] 305800 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 305716 0
Health and Disability Ethics Committees
Ethics committee address [1] 305716 0
Ministry of Health
Health and Disability Ethics Committees
133 Molesworth Street, Thorndon
Wellington 6011
Ethics committee country [1] 305716 0
New Zealand
Date submitted for ethics approval [1] 305716 0
16/03/2020
Approval date [1] 305716 0
Ethics approval number [1] 305716 0
--

Summary
Brief summary
Kawakawa is a versatile herb, endemic to New Zealand, where it is widely used for food, medicinal, and traditional ceremonial purposes by Maori. Kawakawa leaves and fruits are reported to possess medicinal properties and are utilised for a wide range of health conditions not only limited to skin diseases but for the treatment of genitourinary,
gastrointestinal as well as respiratory diseases. A previous study by Butts et al (2019) described that there is a significant number of chemical constituents present in kawakawa leaves with potential pharmacological properties. Therefore, as a candidate for potential functional food applications, examining the bioavailability of kawakawa metabolites for human consumption is required. In-vitro or mechanistic studies carried out with kawakawa leaves and fruits have discovered that they are safe for human consumption and have potential health benefits. With the advent of this, there exists a scientific need to explore the mechanisms of human metabolism and bioavailability upon the ingestion of kawakawa tea. Therefore, the aim of this study is to evaluate the bioavailability of kawakawa metabolites from commercially available kawakawa tea leaves and its effects on other metabolic and biochemical parameters in healthy adults.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 101330 0
Prof Richard Mithen
Address 101330 0
Liggins Institute
University of Auckland
85 Park Road
Grafton
Auckland 1023
Country 101330 0
New Zealand
Phone 101330 0
+64 27 201 7675
Fax 101330 0
Email 101330 0
[email protected]
Contact person for public queries
Name 101331 0
Prof Richard Mithen
Address 101331 0
Liggins Institute
University of Auckland
85 Park Road
Grafton
Auckland 1023
Country 101331 0
New Zealand
Phone 101331 0
+64 27 201 7675
Fax 101331 0
Email 101331 0
[email protected]
Contact person for scientific queries
Name 101332 0
Dr Farha Ramzan
Address 101332 0
Liggins Institute
University of Auckland
85 Park Road
Grafton
Auckland 1023
Country 101332 0
New Zealand
Phone 101332 0
+64 22 4505345
Fax 101332 0
Email 101332 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All of the Individual participant data (including data dictionaries) collected during the trial will be available after de-identification, along with the study protocol.
When will data be available (start and end dates)?
Data will be available beginning 3 months following the first publication of study results and ending 36 months following publication.
Available to whom?
Data will be available to investigators who provide a methodologically sound proposal approved by the Study Steering Committee, for use to achieve the aims in the approved proposal. Proposals should be directed to the principal investigator. To gain access, requests will need to sign a data access agreement.
Available for what types of analyses?
For use to achieve the aims in an approved proposal.
How or where can data be obtained?
Proposals should be directed to the principal investigator ([email protected]). To gain access, requests will need to sign a data access agreement.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
7564Study protocol  [email protected]
7565Informed consent form  [email protected] 379568-(Uploaded-07-04-2020-14-47-46)-Study-related document.doc



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseAcute Effects of Kawakawa (Piper excelsum) Intake on Postprandial Glycemic and Insulinaemic Response in a Healthy Population.2022https://dx.doi.org/10.3390/nu14081638
N.B. These documents automatically identified may not have been verified by the study sponsor.