ANZCTR - Registration

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial registered on ANZCTR

Registration number

ACTRN12621000001897

Ethics application status

Approved

Date submitted

17/08/2020

Date registered

7/01/2021

Date last updated

8/12/2024

Date data sharing statement initially provided

7/01/2021

Type of registration

Retrospectively registered

Titles & IDs

Public title

Characterising the Pre-diabetic Asian and Caucasian Phenotype: the ‘TOFI’ Profile – 3-year Follow-up

Scientific title

Characterising the Pre-diabetic Asian and Caucasian Phenotype: the ‘TOFI’ Profile – 3-year Follow-up: identifying biomarkers of diabetic susceptibility and resilience using a metabolomics platform

Secondary ID [1]

Nil

Universal Trial Number (UTN)

U1111-1249-9953

Trial acronym

TOFI_F/U

Linked study record

This is a 3-year follow up study to ACTRN12616000362493

Health condition

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

Diabetes

Condition category

Condition code

Diet and Nutrition

Obesity

Metabolic and Endocrine

Diabetes

Intervention/exposure

Study type

Observational

Patient registry

False

Target follow-up duration

Target follow-up type

Description of intervention(s) / exposure

The cross-sectional TOFI Asia study recruited Asian Chinese and European Caucasian adults resident in 2016 in Auckland, New Zealand. Participants were across a wide range of age (18-70 years), body weight, BMI (body-mass index (BMI) between 20-45 kg/m2) and glycaemia; with both normoglycaemic and moderately hyperglycaemic (pre-diabetic) included. Current or prior diagnosis of type 2 diabetes (T2D) was an exclusion criterion. The cohorts were matched for gender, age and BMI. Phenotype characteristics were measured once in the fasted state and these included anthropometry, body composition including whole body, visceral and ectopic organ fat, and clinical blood biomarkers related to T2D risk, in addition to serum metabolomics and faecal microbiome. The anticipated duration of the assessments is approximately 2 hours

In order to determine whether these markers may predict who worsens towards and/or develops diabetes, longitudinal follow up will be conducted. The 3-year follow-up study will measure anthropometry and fasted blood samples once in the fasted state. Participants will also have once dual-energy x-ray absorptiometry (DXA) scan to determine total and regional body fat, and collect a stool/faecal sample, for gut microbiome.

100 female participants, due to gender differences in body composition, will additionally undertake a single Magnetic Resonance Imaging and Spectroscopy (MRI/S) scan, to determine ectopic and/or non-adipose tissue organ fat in pancreas and liver. They will also complete a short sub-maximal cardiorespiratory fitness (CRF) test. The MRI/S scan will take about 40 minutes to complete.
A subset of these women (n=25) who additionally also had their MRI/S scan will be invited to have a single intravenous glucose tolerance test (ivGTT) as a measure of insulin secretion in the fasted state. The test will take 1 hour and will involve

Will also recruit a new cohort of Asian Chinese and Caucasian participants, to the study, who will undergo baseline testing (as done in 2016 for the TOFI_Asia participants) and subsequent 3 year follow-up in 2023-24. All new participants will meet the following criteria: Asian (mainland Chinese; Hong Kong, Taiwan, Singapore or Malaysian Chinese; or Korean) or Caucasian European ethnicity, aged 18-70 years old, normal weight or overweight with a body mass index (BMI=weight/height2) of between 20-50kg/m2, but are otherwise healthy.
Participants will be matched for gender, age and BMI. Phenotype characteristics that will be measured will include anthropometry, body composition and clinical blood biomarkers related to T2D risk, in addition to serum metabolomics and faecal microbiome.

Intervention code [1]

Not applicable

Comparator / control treatment

Not applicable

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Characterise the healthy vs prediabetic profile for type 2 diabetes based on blood biomarkers (including established biomarkers i.e., fasting plasma glucose, insulin, HbA1c, full lipid profile, liver function tests and novel metabolomic biomarkers) and body composition (using DeXA and MRI/S). This is a composite primary outcome of both blood biomarkers and body composition.

Timepoint [1]

3 years post-enrolment

Primary outcome [2]

Analysis of pancreas and liver fat deposition using untargeted LC-MS methodology in a subgroup of 100 female participants.

Timepoint [2]

3 years post-enrolment

Primary outcome [3]

Identify novel plasma metabolomic markers, that are predictive of pancreas and liver fat deposition and risk of developing type 2 diabetes in a subgroup of 100 female participants.

Timepoint [3]

3 years post-enrolment

Secondary outcome [1]

Determine the impact of MRI determined pancreas and liver fat on pancreatic beta-cell function and insulin secretion using an intravenous glucose tolerance test (iVGTT) in a subgroup of 25.

Timepoint [1]

3 years post-enrolment.
2-stepped 30-minute tests with blood samples collected at -10, 0, 2, 4, 6, 10,25, 30, 32, 34, 36, 40, 55 and 60 minutes for iVGTT.

Secondary outcome [2]

Determine cardiorespiratory fitness as assessed by the YMCA cycle ergometer submaximal test in 100 women.

Timepoint [2]

3 years post-enrolment.
Steady-state heart rate (SSHR) will be calculated as an average HR recorded during the 2nd and 3rd minute of each stage of the YMCA Cycle Ergometer Submaximal Exercise Test.

Eligibility

Key inclusion criteria

Participants of both gender,
(i) between 18–70 years
(ii) BMI 20–45 kg/m2
(iii) both parents of the same ethnic origin, either European Caucasian or Asian Chinese (including mainland China, Singapore, Malaysia, Hong Kong, Taiwan, and Korea)
(iv) normo- or dysglycaemic (fasting plasma glucose, FPG: 5·6–6·9 mmol/L)

Minimum age

18 Years

Maximum age

70 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

*Recent body weight loss/gain >10%, within previous 3 months
*Recent bariatric surgery, within previous 6 months
*Significant current disease
*Pregnant or breastfeeding women
*Standard exclusions for DXA and MRI scanning techniques, including cardiac pacemaker

Study design

Purpose

Screening

Duration

Longitudinal

Selection

Defined population

Timing

Prospective

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

Actual

2/03/2020

Date of last participant enrolment

Anticipated

30/06/2021

Actual

6/08/2021

Date of last data collection

Anticipated

30/06/2024

Actual

6/08/2021

Sample size

Target

400

Accrual to date

Final

204

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Auckland

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

National Science Challenge High Value Nutrition (HVN)

Address [1]

Building 505
85 Park Road, Grafton
Auckland, 1023

Country [1]

New Zealand

Primary sponsor type

University

Name

University of Auckland

Address

Level 10, Building 620
49 Symonds St
Auckland
1010

Country

New Zealand

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Southern Health and Disability Ethics Committees

Ethics committee address [1]

Ministry of Health
Freyberg Building
20 Aitken Street
PO Box 5013
Wellington
6011

Ethics committee country [1]

New Zealand

Date submitted for ethics approval [1]

27/10/2019

Approval date [1]

26/02/2020

Ethics approval number [1]

16/STH/23/AM09

Summary

Brief summary

Background: People of Asian descent are at much higher risk of poor metabolic health and diabetes at a younger age and a lower body weight than those of European Caucasian descent. The reason why some individuals are more susceptible than others and what controls their diabetes risk may lie in the storage of body fat and may be identified through early changes in serum metabolite profile. Gaining even small amounts of body weight can lead to the fat ‘spilling over’ from adipose tissue and into important organs such as the muscle, liver and pancreas, which in turn may significantly increase risk of disease. Often known as the TOFI profile – ‘Thin on the Outside, Fat on the Inside’ – people who appear ostensibly slim and/or mildly overweight can develop diabetes whilst those who are very overweight and/or obese may not. Few predictive biomarkers of early diabetes risk and propensity to susceptibility or resilience have yet been determined.
Objective: To investigate diabetic risk profile, susceptibility and resilience to weight gain and increasing adiposity in a population of Asian Chinese and Caucasian adults using body composition and metabolomic techniques; and, to conduct 3-year follow-up to determine whether these markers may predict who worsens towards and/or develops frank diabetes.
Design: This is a longitudinal follow-up study of 400 participants, aged 18-70 years, of Asian Chinese (n=200) or Caucasian European (n=200) ethnicity. At baseline and 3-year follow-up, fasting blood samples will be collected to assess diabetic profile based on fasting plasma glucose, and also for untargeted metabolomics profiling; whole body and segmental fat free mass and adipose tissue fat mass will be measured on a single occasion using DEXA scanning; and in a subset of 100 individuals ectopic lipid storage in key organs including liver, pancreas and muscle will be measured using MRI/S.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Sally D Poppitt

Address

University of Auckland Human Nutrition Unit
18 Carrick Place
Mt Eden
Auckland 1024

Country

New Zealand

Phone

+64 96305160

Fax

s.poppitt@auckland.ac.nz

Contact person for public queries

Name

Louise Lu

Address

University of Auckland Human Nutrition Unit
18 Carrick Place
Mt Eden
Auckland 1024

Country

New Zealand

Phone

+64 96305160

Fax

louise.lu@auckland.ac.nz

Contact person for scientific queries

Name

Ivana Sequeira

Address

University of Auckland Human Nutrition Unit
18 Carrick Place
Mt Eden
Auckland 1024

Country

New Zealand

Phone

+64 96305160

Fax

i.sequeira@auckland.ac.nz

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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. However, if this is necessary additional consent will be obtained from participants to allow the use of data for other studies.

What supporting documents are/will be available?

Doc. No.	Type	Attachment
7404	Study protocol	379483-(Uploaded-19-03-2020-13-11-29)-Study-related document.docx
7405	Informed consent form	379483-(Uploaded-19-03-2020-13-11-51)-Study-related document.docx
7406	Ethical approval	379483-(Uploaded-19-03-2020-13-12-17)-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.

Trial Review

Registering a new trial?

Documents added manually

Documents added automatically