Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000318886
Ethics application status
Approved
Date submitted
20/01/2021
Date registered
22/03/2021
Date last updated
25/01/2023
Date data sharing statement initially provided
22/03/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
The New Zealand Synergy Study for diabetes prevention in Asian Chinese
Scientific title
The New Zealand Synergy Study: The effect of a dietary intervention on diabetes biomarkers in pre-diabetic Asian Chinese and European Caucasian cohorts
Secondary ID [1] 300917 0
Nil known
Universal Trial Number (UTN)
U1111-1255-2348
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prediabetes 316885 0
Condition category
Condition code
Metabolic and Endocrine 315062 315062 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This trial will be a 2 week, fully diet controlled, parallel design, 3 treatment intervention, conducted within the Human Nutrition Unit (HNU) residential facility.
The effect of dietary intervention will be assessed in:
-Asian Chinese on Healthy diet (HD) – control
-Asian Chinese on Synergy+ diet (SD) – NZ synergy diet.
-Caucasian European on Healthy diet (HD) – control
All Caucasian participants will be enrolled in the Healthy diet arm while the Chinese participants will be allocated by chance to either the Healthy diet or the Healthy Synergy+ diet arms.

The macronutrient composition of the diets are as follows:

1) Healthy diet (HD) – control:
~55 en% carbohydrate [range 45-60en%], with <10en% added sugars; moderate (soluble) fibre, moderate glycaemic index (GI) [56-69 units]
~30en% total fat, with <10en% saturated fat
~15en% protein, with <80g/week red meat

2) Synergy+ Diet (SD):
~45 en% carbohydrate [range 45-60en%], with <5en% added sugars; high (soluble) fibre, low glycaemic index (GI) [<55 units]
~30en% total fat, with <10en% saturated fat; high monounsaturated fatty acid/polyunsaturated fatty acid ratio (MUFA/PUFA) including n-3 PUFA (docosahexaenoic acid, eicosapentaenoic acid)
~25en% protein, with <40g/week red meat; high dairy (whey), marine and plant origin food

Both HD and SD intervention diets will be based on a typical Asian Chinese-style diet. The HD will adhere to New Zealand Ministry of Health healthy eating (Ministry of Health, 2015), and National guidelines of China (Pagoda Diet) for good metabolic health. The SD will also adhere to New Zealand Ministry of Health healthy eating (Ministry of Health, 2015), and National guidelines of China (Pagoda Diet) for good metabolic health, and matched to the control arm and will additionally include a combination of foods hypothesised to further improve glycaemic/metabolic health outcomes. All diets will be approved by a Registered Dietitian and the diets will be administered by trained Research Staff at the Human Nutrition Unit.
Daily energy intake will be calculated based on 1.4 x predicted basal metabolic rate (BMR), using gender- and age-specific equations. This is equivalent to a sedentary day, where physical activity level (PAL) is 1.4 x BMR. Participants will be kept in energy balance throughout the intervention to ensure no weight gain or loss. The diet will be prepared in 0.5MJ increments (e.g. 6, 6.5, 7, 7.5, 8, 8.5MJ) and hence individualised for each participant.

Compliance to diet will be monitored throughout the 14 day study. All foods, beverages and snacks will be provided. Breakfast and dinner meals will be consumed under supervision. Lunch and snacks may be eaten outside the HNU. No other foods will be allowed. Nitrogen balance will be measured on Day 7, based on 24-h urine collection.

Intervention code [1] 317236 0
Prevention
Comparator / control treatment
The Healthy control (HD) diet will be comparator to assess the effect of dietary intervention and is designed by investigators using guidelines specified by the New Zealand Ministry of Health healthy eating (Ministry of Health, 2015), and National guidelines of China (Pagoda Diet). The macronutrient composition will comprise ~55 en% carbohydrate [range 45-60en%], with <10en% added sugars; moderate (soluble) fibre, moderate glycaemic index (GI) [56-69 units]
~30en% total fat, with <10en% saturated fat
~15en% protein, with <80g/week red meat
10 Asian Chinese participants and 10 Caucasian European participants will be in the Healthy Control Arm.
Control group
Active

Outcomes
Primary outcome [1] 323367 0
Change in plasma metabolome
Timepoint [1] 323367 0
Baseline (0w) and 2 weeks (2w) post-intervention commencement
Secondary outcome [1] 381674 0
Composite change in established plasma markers of obesity and type 2 diabetes; fasting plasma glucose (FPG), postprandial 2-h glucose (oral glucose tolerance test, OGTT), HbA1c, fasting insulin, C-peptide
Timepoint [1] 381674 0
Baseline (0w) and 2 weeks (2w) post-intervention commencement
Secondary outcome [2] 381675 0
Composite change in both basal metabolic rate (BMR) and post prandial energy expenditure (glucose induced thermogenesis, GIT) assessed using indirect calorimetry

Timepoint [2] 381675 0
BMR: will be tested fasted for 30 minutes at Baseline (0w) and 2 weeks (2w) post-intervention commencement

GIT: will be tested at Baseline (0w) and 2 weeks (2w) post-intervention commencement during a 75g oral glucose tolerance test (OGTT)
7.42-7.45am: t=0 min, fasted blood sample
8-9.30am: blood sample every 15 min, t=15min to t=90 min
9.45am: final blood sample t=120min,
Secondary outcome [3] 381676 0
Feacal microbiome
Timepoint [3] 381676 0
Baseline (0w) and 2 weeks (2w) post-intervention commencement
Secondary outcome [4] 390770 0
Change in clinical markers of obesity and type 2 diabetes - blood lipid profile (TC, LDL-C, HDL-C, TAG)
Timepoint [4] 390770 0
Baseline (0w) and 2 weeks (2w) post-intervention commencement
Secondary outcome [5] 392088 0
Regulation of the aryl hydrocarbon receptor (AhR) activity in faecal sample
Timepoint [5] 392088 0
Baseline (0w) and 2 weeks (2w) post-intervention commencement
Secondary outcome [6] 392090 0
Change in clinical markers of obesity and type 2 diabetes - blood liver function tests
Timepoint [6] 392090 0
Baseline (0w) and 2 weeks (2w) post-intervention commencement
Secondary outcome [7] 392091 0
Change in clinical markers of obesity and type 2 diabetes - blood inflammatory markers and blood PBMCs for immune profiling
Timepoint [7] 392091 0
Baseline (0w) and 2 weeks (2w) post-intervention commencement
Secondary outcome [8] 392092 0
Change in blood clinical markers of obesity and type 2 diabetes related peptides, including adiponectin, amylin, glucagon, GLP-1
Timepoint [8] 392092 0
Baseline (0w) and 2 weeks (2w) post-intervention commencement
Secondary outcome [9] 392093 0
Change in epigenetic, SNP and miRNA markers of T2D in blood
Timepoint [9] 392093 0
Baseline (0w) and 2 weeks (2w) post-intervention commencement
Secondary outcome [10] 392094 0
Change in urine metabolome profile
Timepoint [10] 392094 0
Baseline (0w) and 2 weeks (2w) post-intervention commencement

Eligibility
Key inclusion criteria
• Male and female
• Asian Chinese and European Caucasian
• Aged between 18-60 years
• BMI 24-40 kg/m2
• Fasting plasma glucose (FPG) in prediabetic range, 5.6 – 6.9 mmol/L
• Otherwise healthy, as per self-report
• Agreement to participate in a residential study
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Type 1 or type 2 diabetes mellitus
• Low serum iron and ferritin levels
• Medications controlling glycaemia
• Current or history of significant disease including cardiovascular disease; pancreatic disease, or other digestive diseases including inflammatory bowel syndrome/disease, ulcerative colitis, Crohn's disease; cancer
• Recent body weight loss/gain >10% within previous 3 months or taking part in an active diet program; or current medications for weight loss
• Previous bariatric surgery
• Smoker, current or in previous 6 months
• Recreational drug user, current or in previous 6 months
• Dislike or unwilling to consume food items included in the study (including animal products), or hypersensitivities or allergies to these foods
• Unwilling/unable to comply with study protocol
• Participation in other clinical study, current or in previous 6 months
• Pregnant or breastfeeding women, current or in previous 6 months
• Considered unsuitable to participate by the PI
• Blood donation within previous 3 months.


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 to the investigators
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Other
Other design features
Participants will be blinded to whether they will be receiving the Healthy diet (HD) or the Synergy diet (SD).
All Caucasian participants will be enrolled in the Healthy diet arm while the Chinese participants will be allocated by chance to either the Healthy diet or the Synergy diet arms so that responses and differences in the diabetes biomarker profile can be tested.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
A priori modelling of sample size required to identify the change in plasma metabolomic biomarker ‘fingerprint’ in response to a 2 week dietary intervention as significant has been estimated using data from our previous TOFI_Asia study (ACTRN12616000362493). This was a cross sectional analysis where plasma metabolomics biomarkers were measured on 1 occasion (baseline) using state-of-the-art LC-MS in a cohort of ~400 Asian Chinese and European Caucasians. Using variance data from this study (plasma metabolites) and estimates of expected effect size (effect of diet over 2 weeks – dichotomous ‘fingerprint’ of metabolites between ethnicities converge or diverge or unchanged), response of the metabolites was modelled across a range of sample sizes. In order to be able to identify a significant difference between the 2 ethnicity ‘fingerprints’ using PLS-DA modelling, it was estimated that n=10 individuals was required in each of the 2 ethnicity cohorts.
All statistical models generated during data analysis in the residential study will be adjusted for potential confounding (if any) due to inclusion of both genders in the study design, which may influence the response/outcome variables of interest.



Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/04/2021
Actual
3/05/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
30
Accrual to date
15
Final
Recruitment outside Australia
Country [1] 22460 0
New Zealand
State/province [1] 22460 0
Auckland

Funding & Sponsors
Funding source category [1] 305363 0
Government body
Name [1] 305363 0
New Zealand Ministry of Business, Innovation and Employment (MBIE) , National Science Challenge funding.
Country [1] 305363 0
New Zealand
Primary sponsor type
University
Name
The University of Auckland
Address
Level 10, Building 620
49 Symonds St
Auckland 1010
New Zealand
Country
New Zealand
Secondary sponsor category [1] 305739 0
None
Name [1] 305739 0
Not Applicable
Address [1] 305739 0
Not Applicable
Country [1] 305739 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305696 0
Southern Health and Disability Ethics Committees (HDECs) New Zealand
Ethics committee address [1] 305696 0
Health and Disability Ethics Committee
Ministry of Health
133 Molesworth Street, PO Box 5013,
Wellington 6011
Ethics committee country [1] 305696 0
New Zealand
Date submitted for ethics approval [1] 305696 0
26/03/2020
Approval date [1] 305696 0
09/09/2020
Ethics approval number [1] 305696 0
20/STH/51

Summary
Brief summary
Researchers aim to identify blood, urine and faecal markers of type 2 diabetes (T2D) risk that differ between ethnicities; and undertake nutritional interventions that target these biomarkers.
Our previous study showed that Asian Chinese had a unique ‘fingerprint’ of diabetes markers with worse blood glucose (blood sugar), lipids (blood fats), and different novel metabolomic markers when they were still younger and outwardly-slim than matched European Caucasian counterparts.
The reason for this difference is not known, and so in this current study we will try to find out what causes the difference.
One possibility is that the markers are different due to completely different home diets.
Therefore, we will test whether differences in the novel ‘metabolomics’ blood markers are completely due to diet and also assess whether diet with additional nutrients may together (synergistically) be beneficial in changing the profile of these novel blood markers.
In order to do so, we will design two healthy diets based on the New Zealand and the Chinese dietary guidelines for improving metabolic health. The two diet arms will be:
1) HEALTHY DIET (‘control’ diet, HD): which adheres to NZ and Chinese national dietary guidelines for good metabolic health
2) HEALTHY SYNERGY+ DIET (SD): which adheres to NZ and Chinese national dietary guidelines for good metabolic health and includes some additional nutrients** hypothesised to have further improve metabolic health.
** Examples are whole foods such as omega-3 rich fish, more fibre, nuts and seeds, meat with less saturated fats. Both diets are healthy and matched with each other for energy content.
All Caucasian participants will be enrolled in the Healthy diet arm while the Chinese participants will be allocated by chance to either the Healthy diet or the Healthy Synergy+ diet arms.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 101262 0
A/Prof Jennifer Miles-Chan
Address 101262 0
University of Auckland
Human Nutrition Unit,
18 Carrick Place, Mt Eden, Auckland 1024
Country 101262 0
New Zealand
Phone 101262 0
+64 09 6305160
Fax 101262 0
Email 101262 0
[email protected]
Contact person for public queries
Name 101263 0
Dr Ivana R Sequeira
Address 101263 0
University of Auckland
Human Nutrition Unit,
18 Carrick Place, Mt Eden, Auckland 1024
Country 101263 0
New Zealand
Phone 101263 0
+64 09 6301162
Fax 101263 0
Email 101263 0
[email protected]
Contact person for scientific queries
Name 101264 0
Dr Ivana R Sequeira
Address 101264 0
University of Auckland
Human Nutrition Unit,
18 Carrick Place, Mt Eden, Auckland 1024
Country 101264 0
New Zealand
Phone 101264 0
+64 09 6301162
Fax 101264 0
Email 101264 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
This is in accordance to National Health and Disability Ethics Committees application that all data generated will only be used for this study only.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
10276Study protocol    379551-(Uploaded-25-01-2023-07-07-17)-Study-related document.docx
10277Informed consent form    379551-(Uploaded-25-01-2023-07-06-27)-Study-related document.docx
10278Ethical approval    379551-(Uploaded-18-03-2021-13-08-37)-Study-related document.pdf



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.