Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000275763
Ethics application status
Approved
Date submitted
27/01/2022
Date registered
14/02/2022
Date last updated
14/02/2022
Date data sharing statement initially provided
14/02/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Impact of kawakawa on energy metabolism and human physiology
Scientific title
Tuhauora ka tahi: Effects of kawakawa containing beverage on the energy metabolism and physiology in healthy human volunteers
Secondary ID [1] 304650 0
None
Universal Trial Number (UTN)
U1111-1273-6221
Trial acronym
Tuhauora ka tahi
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Energy metabolism 322596 0
Obesity 322599 0
Condition category
Condition code
Metabolic and Endocrine 320211 320211 0 0
Normal metabolism and endocrine development and function
Diet and Nutrition 320213 320213 0 0
Other diet and nutrition disorders
Diet and Nutrition 322509 322509 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will examine the postprandial thermogenic and substrate utilisation effect of kawakawa containing beverage. As previously reported, the postprandial state lasts for approximately 4-5 h post-meal period (1). Thus, the study will require participants to attend the Clinical Research Unit (CRU), of the Liggins Institute on each intervention visit for a period of 3 hours. Participants will complete a screening assessment (Visit 1) and if eligible for entry into the trial will be required to visit Liggins Institute in fasted condition. Participants will be provided with a standardised meal (Vegetable pulao, 300gm, 526Kcalories) supplied from muscle chow NZ (www.musclechow.co.nz) to eat the evening before each study visit to reduce variability in the fasting substrate oxidation profile. This meal will be of identical macronutrient composition and energy content within- and between-participants. Participants will be advised to abstain from intense exercise, caffeinated or herbal drinks, spices and alcoholic drinks in the 24 hrs prior to the study visits. Participants will be asked to arrive at the CRU in the morning, following a 12 h fast.
Screening visit :
This screening visit will take place prior to the commencement of the intervention period. The subject will be asked to attend the Clinical Research Unit (CRU) of the Liggins Institute for a 30 minute visit. Written and verbal description of the study will be provided and informed consent obtained from eligible participants. Subjects who meet the inclusion/exclusion criteria will then be registered into the trial. Demographics (age and ethnicity) and anthropometry (height, body weight, BMI) will be recorded. Participant will also be asked to complete screening questionnaire.
Prior to their intervention visits, participants will have their body composition assessed by dual Energy X-Ray Absorptiometry (iDXA, GE-Lunar) at the Clinical Research Unit (CRU) of the Liggins Institute. DXA is based on the 3-compartment model of body composition, and uses two x-ray energies to measure body fat mass, lean mass, and bone mineral. The participant is required to lie recumbent on the open scanner bed for ~10 minutes. Body composition comprising total body fat, fat-free soft tissue and bone mineral content as well as regional fat deposition will be determined from DXA whole-body and segmental scans. Fat-free mass is the main determinant of resting energy expenditure, and hence this information will enable us to mathematically adjust our metabolic rate measurements accordingly.
Intervention visit:
Four acute intervention visits (4 hrs each, separated by at least 48 hrs washout). Treatment-1: 15 mL base beverage formulation containing Livaux gold kiwifruit powder, lemon juice, ginger, turmeric. Washed down with 235 mL water.Treatment-2: 15 mL base formulation + aqueous kawakawa infusion equivalent to tea made with 16 g kawakawa per litre of hot water. Washed down with 235 mL water.Treatment-3: Aqueous kawakawa infusion equivalent to tea made with 16 g kawakawa per litre of hot water. Control: Hot water (250mL)
Upon arrival, the participant’s anthropometric measurements (weight) will be taken and a spot urine sample collected. Participants will then be asked to sit in a comfortable seat, in a quiet, temperature-controlled (20-22°C) laboratory. Body temperature will be measured using a tympanic thermometer to exclude the presence of fever. A peripheral venous cannula will be inserted by the Research Nurse for repeated blood sampling. A 16mL fasting baseline blood sample will be collected, and baseline Visual Analogue Scale (VAS) ratings of hunger, comfort and nausea will be measured using standard VAS methods. Participants will then be connected to equipment for continuous physiological monitoring. The respiratory gas exchange will be measured non-invasively by indirect calorimetry. Continuous, non-invasive, haemodynamic monitoring will also be undertaken. Participants will also be instrumented with autonomous wireless temperature sensors to measure changes in skin temperature. After 30 mins of baseline measurements by indirect calorimetry using an open-circuit ventilated hood system, the hood will be removed and participants will be provided with the randomised test beverage (t= 0 mins) and requested to consume this in entirety within 10 mins prior to recommencing indirect calorimetry measurements. Following 3 h of postprandial monitoring, participants will be invited to eat a controlled lunch meal ad libitum to objectively assess appetite and satiety. Participants will be permitted to watch calm documentaries or films during cardio-metabolic monitoring. Throughout the morning, a total of 6x blood samples will be collected after the test beverage at the following time-points: t= 15, 30, 60, 90, 120, and 180. A total volume of 70mL will be taken at each study visit.

Reference
1. Monnier L, Colette C. Target for glycemic control: concentrating on glucose. Vol. 32 Suppl 2, Diabetes care. 2009.
Intervention code [1] 321001 0
Prevention
Comparator / control treatment
Treatment-4: Hot water (250mL)
Control group
Active

Outcomes
Primary outcome [1] 328083 0
To examine the effect of beverage formulation on metabolic rate (energy expenditure).
metabolic rate will be measured using an Indirect calorimeter: Respiratory gas exchange will be measured non-invasively by indirect calorimetry using an open-circuit ventilated hood system (Quark, Cosmed Srl, Italy). Energy expenditure (EE) and respiratory quotient (RQ) are calculated from the rates of oxygen consumption (VO2) and carbon dioxide (VCO2) production.
Timepoint [1] 328083 0
Metabolic responses will be assessed both at fasting and continuously over the postprandial period (3hr)
Primary outcome [2] 330451 0
To examine the effect of beverage formulation respiratory quotient (relative substrate utilisation).
Timepoint [2] 330451 0
Metabolic responses will be assessed both at fasting and continuously over the postprandial period (3hr)
Secondary outcome [1] 397541 0
To examine the impact of beverage formulation on the plasma metabolic profiles using liquid chromatography with mass spectrometry (LC-MS) techniques.
Timepoint [1] 397541 0
Fasting blood samples will be collected. After the intervention, blood samples will be collected at 15, 30, 60, 90, 120 and 180 mins
Secondary outcome [2] 397542 0
To examine the impact of beverage formulation on the urine metabolic profiles using liquid chromatography with mass spectrometry (LC-MS) techniques.
Timepoint [2] 397542 0
Urine samples will be collected at 0 and 180 min (3hr).
Secondary outcome [3] 397544 0
To examine the impact of beverage formulation on postprandial plasma glucose metabolism. Plasma glucose will be measured using a Roche Cobas c311 autoanalyser by enzymatic colourimetric assay.
Timepoint [3] 397544 0
Fasting blood samples will be collected. After the intervention, blood samples will be collected at 15, 30, 60, 90, 120 and 180 mins.
Secondary outcome [4] 397545 0
To measure the impact of beverage formulation on plasma insulin. Plasma insulin will be measured on a Roche Cobas e411 by electro-chemiluminescence immunoassay.
Timepoint [4] 397545 0
Fasting blood samples will be collected. After the intervention, blood samples will be collected at 15, 30, 60, 90, 120 and 180 mins.
Secondary outcome [5] 397546 0
To examine the impact of beverage formulation on the cardiovascular profile (heart rate, blood pressure).
Timepoint [5] 397546 0
Continuous heart rate monitoring will be monitored. Blood pressure will be monitored at regular time points, first at the baseline and then postprandially every hour until the end of each intervention visit.
Secondary outcome [6] 397547 0
To examine the impact of beverage formulation on body temperature. Participants will be instrumented with autonomous wireless temperature sensors (Thermochron iButton model DS1922H, Maxim) in 12 locations: forehead, upper-back, lower-back, chest, abdomen, bicep, forearm, hand, quadriceps, hamstring, front calf and back calf. A weighted-mean skin temperature will be calculated.
Timepoint [6] 397547 0
The temperature will be measured continuously from the start and over the postprandial period of 3hr
Secondary outcome [7] 405469 0
To examine the impact of beverage formulation on the changes of visual analogue scale (VAS) scores of hunger, comfort, nausea; appetite and satiety assessed via an ad-lib meal.
VAS will be used following the methodology of Blundell et al (1). Participants will mark their responses by placing a vertical line across the 100-mm scale according to their subjective feelings (Figure 3). For example: How hungry do you feel? (a) I am not hungry at all (b) I am as hungry as I've ever been. All these parameters would be analysed together as a composite outcome

Reference:
1. Blundell J, De Graaf C, Hulshof T, Jebb S, Livingstone B, Lluch A, et al. Appetite control: Methodological aspects of the evaluation of foods. Vol. 11, Obesity Reviews. Obes Rev; 2010. p. 251–70.
Timepoint [7] 405469 0
VAS will be used at baseline and every hour postprandially
Secondary outcome [8] 405482 0
To quantify the impact of beverage formulation on metabolic and inflammatory-related gene expression.
Blood chemistry analysis including whole blood count to evaluate changes in white blood cell populations in response to intervention ingestion as a measure of immune activation.
Plasma and peripheral blood mononuclear cell (PBMCs) gene expression will be performed following total RNA extraction for measurement of changes in expression of genes involved in metabolic homeostasis (such as CPT1A, FAS, UCP) and also in inflammatory gene expression (such as TNF-a, MCP-1, IL-1ß) and microRNAs. These will be assessed by either RT-PCR from fasting samples and at 1 & 2 hours following intervention consumption.
Timepoint [8] 405482 0
These will be obtained at fasting, and at 1 &2 hours after the end of fasting.

Eligibility
Key inclusion criteria
Participants will be eligible to participate if:
• Gender: both males and females. To control for menstruation cycle variation in results, female participants would be required to come in the same phase of their cycle for all the intervention visits.
• Age: 18-45 yr.
• BMI: 18-30kg/m2
• Non-smokers
• Self-reported not consuming dietary supplements
• Self-reported healthy
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Participants will be excluded from participation if they:
• 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.
• Have a medical history precluding a healthy state: history of myocardial infarction, angina, stroke, cancer or pre-existing diabetes
• Are Claustrophobic
• Have recently gained or lost around >5% body weight

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 interventions 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)
The allocation sequence will be set up 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, Four-arm crossover trial
Phase
Not Applicable
Type of endpoint/s
Efficacy
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
21/02/2022
Actual
Date of last participant enrolment
Anticipated
31/08/2022
Actual
Date of last data collection
Anticipated
30/10/2022
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment outside Australia
Country [1] 23928 0
New Zealand
State/province [1] 23928 0
Auckland

Funding & Sponsors
Funding source category [1] 309012 0
Other Collaborative groups
Name [1] 309012 0
High Value Nutrition (HVN)
Country [1] 309012 0
New Zealand
Primary sponsor type
University
Name
Liggins Institute, The University of Auckland
Address
85 Park Road, Grafton, 1023
Country
New Zealand
Secondary sponsor category [1] 311835 0
None
Name [1] 311835 0
Address [1] 311835 0
Country [1] 311835 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308898 0
Northern B Health and Disability Ethics Committee
Ethics committee address [1] 308898 0
Ethics committee country [1] 308898 0
New Zealand
Date submitted for ethics approval [1] 308898 0
31/05/2021
Approval date [1] 308898 0
29/06/2021
Ethics approval number [1] 308898 0
21/NTB/119

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 112266 0
Dr Chris Pook
Address 112266 0
Liggins Institute
University of Auckland
85 Park Road
Grafton
Auckland 1023
Country 112266 0
New Zealand
Phone 112266 0
+64 21464234
Fax 112266 0
Email 112266 0
[email protected]
Contact person for public queries
Name 112267 0
Farha Ramzan
Address 112267 0
Liggins Institute
University of Auckland
85 Park Road
Grafton
Auckland 1023
Country 112267 0
New Zealand
Phone 112267 0
+64 22 4505345
Fax 112267 0
Email 112267 0
[email protected]
Contact person for scientific queries
Name 112268 0
Farha Ramzan
Address 112268 0
Liggins Institute
University of Auckland
85 Park Road
Grafton
Auckland 1023
Country 112268 0
New Zealand
Phone 112268 0
+64224505345
Fax 112268 0
Email 112268 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
12326Study protocol  [email protected] 382302-(Uploaded-26-01-2022-11-57-49)-Study-related document.docx
12327Informed consent form  [email protected] 382302-(Uploaded-26-01-2022-11-57-49)-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
No additional documents have been identified.