Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000967987p
Ethics application status
Submitted, not yet approved
Date submitted
13/07/2020
Date registered
28/09/2020
Date last updated
28/09/2020
Date data sharing statement initially provided
28/09/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Assessing metabolic response curves during mixed meal tolerance testing in healthy European males
Scientific title
Assessing metabolic response curves during mixed meal tolerance testing in healthy European males
Secondary ID [1] 301760 0
Nil Known
Universal Trial Number (UTN)
U1111-1249-5558
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes 318218 0
Insulin resistance / hyperinsulinaemia 318219 0
Condition category
Condition code
Metabolic and Endocrine 316230 316230 0 0
Metabolic disorders
Diet and Nutrition 316231 316231 0 0
Obesity
Metabolic and Endocrine 316878 316878 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Observing the metabolic responses following each of three different meals: 75g glucose in 300mL water (using the commercial standard 'Carbotest' drink); mixed meal smoothie (SMMT) (e.g. milk, blueberries, banana, protein powder), and whole food mixed meal (WMMT) (e.g. muesli, milk and fruit with eggs on Vogel's toast). The latter two will be prepared for participants based on the information provided from a three-day food diary and will provide approximately one-third of their personalised daily caloric requirement. The carbohydrate, protein and total fat content of the smoothies and the mixed meals will comprise 55%, 20%, and 25%, respectively, of this energy intake. Foods used may vary slightly depending on caloric requirements.

It is typical, and will be encouraged, for the glucose drink to be consumed within about 5 minutes. Participants will be timed eating the SMMT and WMMT. Ideally these meals will be consumed within 15 minutes.

It is anticipated that each test will take 3-3.5 hours to complete. (e.g. three hours from the commencement of the meal, but allow about 30 minutes for administration and initial cannulation)

Each test will be conducted seven days apart to allow a 'wash-out' between each testing period.
Intervention code [1] 318054 0
Diagnosis / Prognosis
Comparator / control treatment
As described above, there is no separate control group. Each person acts as their own control. The glucose test is the standard baseline currently used for diagnosis/monitoring
Control group
Active

Outcomes
Primary outcome [1] 324417 0
Inter-and intra- individual variability of the plasma glucose assessed by pharmacokinetic parameters (e.g. AUC, time to maximum concentration, maximum concentration and half-life of the response curve)
Timepoint [1] 324417 0
Sampling will occur at baseline then 30 min, 60 min, 120 min, and 180 min. Timing will commence when the participants commence meal consumption.
Primary outcome [2] 324418 0
Inter-and intra- individual variability of the plasma insulin concentrations assessed by pharmacokinetic parameters (e.g. AUC, time to maximum concentration, maximum concentration and half-life of the response curve)
Timepoint [2] 324418 0
Sampling will occur at baseline, 30 min, 60min, 120 min and 180 min. Timing will commence when the participant commences meal consumption.
Primary outcome [3] 324648 0
Inter-and intra- individual variability of the plasma c-peptide levels assessed by pharmacokinetic parameters (e.g. AUC, time to maximum concentration, maximum concentration and half-life of the response curve)
Timepoint [3] 324648 0
Sampling will occur at baseline, 30 min, 60min, 120 min and 180 min. Timing will commence when the participant commences meal consumption.
Secondary outcome [1] 386446 0
There are no secondary outcomes except as described in statistical analysis
Timepoint [1] 386446 0
N/A

Eligibility
Key inclusion criteria

NZ European

Healthy with no recent injuries (acute or chronic)

Currently consuming at least 150g carbohydrate per day for at least two weeks prior to the testing period.

Able to provide informed consent and adhere to research protocols.
Minimum age
20 Years
Maximum age
45 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
Body mass index less than 18 kg/m2

Any food allergy or intolerance, including, but not limited to coeliac disease, lactose intolerance, and nut or egg allergies.

An unwillingness to consume a variety of foods, even in the absence of food allergies or intolerances.

Anyone with a medical condition (illness or injury) that may cause: increased bleeding, poor circulation, poor venous access, or unstable health.

Anyone with a known gastrointestinal disorder, including, but not limited to, inflammatory bowel disease, irritable bowel disease, chronic constipation or diarrhoea, or recent (within 4 weeks) gastrointestinal infection.

Anyone taking medication that can affect blood glucose, phosphate, or lipid levels including (but not limited to): insulin; sulphonylurea medications; metformin; statins; or calcium.

A history of cancer (excluding non-melanoma skin cancers).

Current smokers / vapers or those recently discontinued smoking/vaping (previous three months).

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using Excel random generators
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis
The OGTT with insulin assay will be stratified according to World Health Organisation standards for glucose response and Kraft pattern algorithms as according to Crofts et al. (2016).

The mixed meal tolerance tests will have their c-peptide, insulin and glucose responses drawn for each individual. Insulin and glucose responses will be compared for area-under-the-curve and pharmacokinetic parameters including time to maximum concentration, maximum concentration and half-life of the response curve. Comparisons will be between participants, across the different meals.

A sub-study will perform secondary analysis on the collected data to compare the pharmacokinetic parameters of the insulin to the c-peptide response curves from each individual meal. Curves will be compared using Pearson's correlations

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/10/2020
Actual
Date of last participant enrolment
Anticipated
8/10/2020
Actual
Date of last data collection
Anticipated
30/10/2020
Actual
Sample size
Target
10
Accrual to date
Final
Recruitment outside Australia
Country [1] 22739 0
New Zealand
State/province [1] 22739 0
Auckland

Funding & Sponsors
Funding source category [1] 306190 0
University
Name [1] 306190 0
Auckland University of Technology
Country [1] 306190 0
New Zealand
Primary sponsor type
University
Name
Auckland Universityof technology
Address
90 Akoranga Drive,
Northcote 0627
Auckland
Country
New Zealand
Secondary sponsor category [1] 306663 0
None
Name [1] 306663 0
Address [1] 306663 0
Country [1] 306663 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 306401 0
Northern B Health and Disability Ethics Committees
Ethics committee address [1] 306401 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 306401 0
New Zealand
Date submitted for ethics approval [1] 306401 0
11/03/2020
Approval date [1] 306401 0
Ethics approval number [1] 306401 0
20/NTB/52
Ethics committee name [2] 306402 0
Auckland University of Technology Ethics Committee
Ethics committee address [2] 306402 0
Auckland University of Technology
46 Wakefield Street, Auckland 1010
Private Bag 92006, Auckland 1142
Ethics committee country [2] 306402 0
New Zealand
Date submitted for ethics approval [2] 306402 0
13/07/2020
Approval date [2] 306402 0
Ethics approval number [2] 306402 0

Summary
Brief summary
A comparison of mixed meals (smoothie compared to 'whole food') against the standard oral glucose tolerance test to investigate a) feasibility for use in assessing and monitoring metabolic response and b) use of c-peptide for assessing hyperinsulinaemia.
Chronic hyperinsulinaemia associated with insulin resistance underpins many globally significant chronic diseases, including type 2 diabetes with resultant morbidity and premature mortality and economic burden. Although the relationship between elevated plasma glucose and /or insulin levels and chronic disease is accepted, there are mounting concerns about the methodologies used to diagnose these conditions. The globally standardised oral glucose tolerance challenge, the baseline measure for both glucose and insulin response tests, is standardised so that every adult older than 20 years receives 75g glucose, The fundamental flaw with this procedure is that glucose disposal rates vary depending on sex, lean body mass, physical activity and foods consumed during the previous 72 hours. Further criticisms of the oral glucose challenge include that it does not reflect normal eating patterns, and the excessively high glucose dose. It is hypothesised that a mixed meal tolerance test (a combination of protein, carbohydrate and fats) that is tailored to the participants’ gender, mass and activity status may provide a better platform from which to understand metabolic responses. It may also provide a better platform from which to better understand metabolic responses following dietary interventions to manage metabolic health, such as a low-carbohydrate diet. It is further hypothesised that c-peptide response patterns could be used as a proxy for insulin response patterns but comparative data is lacking.
Recruiting 10 european males for a 3-way cross-over will collect sufficient data for this pilot.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 103758 0
Dr Catherine Crofts
Address 103758 0
A-25
Auckland University of Technology (AUT)
Private Bag 92006
Auckland 1142 , New Zealand
Country 103758 0
New Zealand
Phone 103758 0
+64 9 921 9999
Fax 103758 0
Email 103758 0
[email protected]
Contact person for public queries
Name 103759 0
Dr Catherine Crofts
Address 103759 0
A-25
Auckland University of Technology (AUT)
Private Bag 92006
Auckland 1142 , New Zealand
Country 103759 0
New Zealand
Phone 103759 0
+64 9 921 9999
Fax 103759 0
Email 103759 0
[email protected]
Contact person for scientific queries
Name 103760 0
Dr Catherine Crofts
Address 103760 0
A-25
Auckland University of Technology (AUT)
Private Bag 92006
Auckland 1142 , New Zealand
Country 103760 0
New Zealand
Phone 103760 0
+64 9 921 9999
Fax 103760 0
Email 103760 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?
Anthropometric data, glucose, insulin, c-peptide reponses
When will data be available (start and end dates)?
Starting January 2022; available for a minimum of ten years. (Following that, will be dependent on whether it has been accessed within that time.)
Available to whom?
researchers who provide a methodologically sound proposal, case-by-case basis at the discretion of Primary Sponsor
Available for what types of analyses?
only to achieve the aims in the approved proposal
How or where can data be obtained?
access subject to approvals by Principal Investigator [email protected]


What supporting documents are/will be available?

No Supporting Document Provided



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.