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Trial registered on ANZCTR


Registration number
ACTRN12617000328370
Ethics application status
Approved
Date submitted
23/02/2017
Date registered
2/03/2017
Date last updated
23/07/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Fibre structure of whole grains in blood glucose response
Scientific title
The fibre structure size of whole grains and impact on postprandial blood glucose response of normal glucose tolerant adults and those diagnosed with type 2 diabetes: randomised crossover study
Secondary ID [1] 291064 0
None
Universal Trial Number (UTN)
U1111-1192-5947
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
type 2 diabetes 301859 0
Postprandial blood glucose control 301860 0
Condition category
Condition code
Diet and Nutrition 301540 301540 0 0
Other diet and nutrition disorders
Metabolic and Endocrine 301836 301836 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study is a crossover design to measure the postprandial blood glucose response to wholegrain foods of different fibre particle size. Each food exposure is an intervention of the study. Each wholegrain product is made primarily from wheat, but differs in its degree of food processing and therefore fibre structure particle size. Each wholegrain product will be defined by its fibre particle size, and the glycaemic response it generates when compared to a recognised glucose standard.

The categories of food being tested are:
Bread comparison
* A bread with refined grain components in the same ratio found in whole grains
* A bread made with finely milled whole grains
* A bread made with a mixture of finely milled and partially ground whole grains (i.e. kibbled)
* A bread made with a mixture of finely ground, partially ground and whole grains

Cracker Comparison
* A cracker made with finely milled whole grains
* A cracker made with a mixture of finely ground, partially ground and whole grains

Cereal Comparison
* A cold cereal made with finely milled whole grains
* A cold cereal made with whole grains
* A hot cereal made with finely milled whole grains
* A hot cereal made with whole grains

The postprandial blood glucose response to these foods and relevant controls will be measured inline with accredited Glycaemic Index (GI) testing protocols. This requires study participants to attend a testing facility in person. Each morning of the test participants will arrive at the testing facility having consumed no food since 10pm the night before. Baseline capillary blood glucose will be measured in duplicate. Wholegrain products containing 50 grams of available carbohydrate will be consumed, 250ml of water will be provided with each food. The participant's postprandial blood glucose response will be identified by a series of capillary blood glucose measures. In participants of normal glucose tolerance (NGT), these measures are taken at 15, 30, 45, 60, 90, and 120 minutes after meal commencement. For participants diagnosed with type 2 diabetes (T2), these measures are taken at 15, 30, 45, 60, 90, 120, 150, and 180 minutes, so to record their prolonged blood glucose response. This is a standardised process with all participants tested in the same manner for each exposure. In addition to the 10 wholegrain products being tested, each participant will attend three mornings of a control containing an equivalent amount of carbohydrate. Each test morning will require participants to be present for 2.5 (NGT) to 3.5 (T2) hours. There will be no more than three test mornings per participant per week resulting in a minimum 24 hour washout before the next intervention. With 13 morning exposures in total (10 foods, 3 controls) participant will be enrolled in the study for a minimum five weeks.

Researchers of this study have published widely in this area. Data from each exposure will be measured by researchers and assistants trained to do so inline with the University of Otago's internationally accredited GI testing facility.

Intervention order will randomised by product for the breads, crackers, and two controls (eight mornings). We will then give participants the opportunity to continue testing the cereals and final control (five mornings) in randomised order. If participants choose not to continue and test the cereals we will recruit new participants so that 20 normal glucose participants and 20 participants with type 2 diabetes have tested all wholegrain products. Adherence will be recorded and fidelity with the required preparations: no food from 10pm the night before, a good source of carbohydrate consumed with the evening meal, alcohol restricted and physical activity in the 24 hours standardised before each test morning. Any participants who decides not to complete the study can do so at no disadvantage. However, we will ask them to fill in a short form to determine the reason for not completing the study. If the participant prefers not to fill in such a form they can do so at no disadvantage. To reduce the non-completion rate, a screening visit will occur before any postprandial response is measured. The screening visit is a chance for interested applicants to meet the researchers collecting the data in person, confirm their eligibility, and to be briefed on the expectations of study participation. Should informed consent be provided, participants will then be asked a series of baseline questions and undergo measurements (height, body weight, waist circumferences, glycated haemoglobin and lipid profile).

During this study additional measures will be made during the postprandial blood glucose response. These measures do not involve additional blood samples or invasive measures. They are described clearly as secondary outcomes of this study.
Intervention code [1] 297053 0
Prevention
Intervention code [2] 297054 0
Lifestyle
Comparator / control treatment
This is a cross over design where each participant acts as their own control. The postprandial blood glucose response of the wholegrain products listed above will be compared within category (breads, cereals, crackers) and against glucose standards to consider the effect of food processing and fibre particle size on postprandial blood glucose response of wholegrain products.
Control group
Active

Outcomes
Primary outcome [1] 300945 0
The postprandial blood glucose response as measured by the incremental area under the curve of 10 wholegrain products that differ in fibre particle size.
Timepoint [1] 300945 0
Capillary blood glucose is measured in duplicate a zero minutes (baseline), then at 15, 30, 45, 60, 90, and 120 minutes for normal glucose tolerant participants, and at 15, 30, 45, 60, 90, 120, 150, and 180 minutes for participants with type 2 diabetes.
Secondary outcome [1] 331253 0
The acceptability of the wholegrain products. Palatability measures are adapted from Flint et al (2000); “Reproducibility, power and validity of visual analogue scales in assessment of appetite sensations in single test meal studies”.
Timepoint [1] 331253 0
Palatability is tested on consumption of each test wholegrain product. This test should take under a minute.
Secondary outcome [2] 331254 0
To assess composite measures of the cognition domains recall and reasoning during carbohydrate digestibility. Validated tests (Immediate word recall / delayed word recall / word presentation / simple reaction time task / Stroop / Go-No Go) will be performed by participants on electronic tablets using the Inquisit software to administer and measure responses.

Timepoint [2] 331254 0
We will measure acute recall and reasoning of participants with an interactive test conducted on portable tablets. This will occur during the postprandial meal response of the two cracker carbohydrate foods, and a glucose standard. This interactive test will be done within the postprandial exposure - at the height of the blood glucose response (60 minutes after meal commencement). A baseline measure of the same interactive test will be undertaken on one morning before any meal is consumed, to represent recall and reasoning when fasted. These cognition tests should take under 20 minutes each time.
Secondary outcome [3] 331255 0
Small organic molecule profile of exhaled breath during carbohydrate digestion as measured by mass spectroscopy.
Timepoint [3] 331255 0
We will measure the exhaled gas profile of participants at each of the blood glucose time points (0, 15, 30, 45, 60, 90, 120 minutes from meal commencement and 150 and 180 minutes from meal commencement for participants diagnosed with type 2 diabetes. Participants are required to breathe three normal breaths near a sensor, this should take under a minute each time.
Secondary outcome [4] 332119 0
Satiety due to consumption of the wholegrain products. Measures of satiety are adapted from Flint et al (2000); “Reproducibility, power and validity of visual analogue scales in assessment of appetite sensations in single test meal studies”.
Timepoint [4] 332119 0
Satiety will be measured directly before and after each wholegrain product is consumed, and then at 30, 60, 90, and 120 minutes after meal consumption. These tests should take under a minute each time.

Eligibility
Key inclusion criteria
Participants will be from two separate groups of the population. One group is of participants diagnosed with type 2 diabetes mellitus aged 18 to 75-years recruited through general practices, hospital outpatient clinics, the local diabetes society and services that cater for people with chronic diseases. The second group will be of 18- 75 year olds without diagnosed type 2 diabetes or any evidence of impaired glucose tolerance. Presence of comorbidities will not exclude participation.
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
For all participants pregnancy, lactation, inability or unwillingness to comply with the intervention requirements will exclude participation.

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)
As a cross over study each participant will undergo each intervention. The order of intervention will be randomised. The researcher who determines if a subject is eligible for inclusion in the trial at the screening visit will not be aware the order of intervention the subject will be allocated to during the study.

The intervention order of participants will be randomised by computer generated process off-site by a biostatistician not involved with the screening of participants.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software balanced for first order carry over effects.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Crossover
Other design features
Regarding blinding - participants will not be truly masked as they can visually identify the products they are eating (e.g. determining between a bread and a cracker), this is not plausible. However, within the food categories (bread, cracker, cereal) the exact nature of the food will not be disclosed to participants.
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
We base our estimate of the sample size on a power calculation with an alpha of 0·05 and power of 0·80 to detect within-group differences in primary outcome variable: a clinically relevant 30% difference in postprandial glycaemia (iAUC). We needed 14 participants from each group (NGT and T2) to complete all interventions, however we intend to over recruit and enrol 20 participants from each group into the study to better consider the effect size and the secondary objectives, some of which (2 &3) are more exploratory in nature than the primary objective. Data will be analysed according to intention to treat. A mixed model, which includes a term for order, will be used to analyse the data. Results will be presented as differences (with 95% confidence intervals) between the two interventions. Data may be log transformed before analysis if skewed. Differences in the primary outcome iAUC will be presented as ratios of the geometric means. Analysis will be undertaken in Stata (StataCorp, TX, USA) with the statistician blinded to the primary analysis.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 8616 0
New Zealand
State/province [1] 8616 0
Otago

Funding & Sponsors
Funding source category [1] 295504 0
Charities/Societies/Foundations
Name [1] 295504 0
The Baking Industry Research Trust
Address [1] 295504 0
PO Box 29 265,
Fendalton, Christchurch 8540,
New Zealand
Country [1] 295504 0
New Zealand
Funding source category [2] 295529 0
Other
Name [2] 295529 0
Riddet Institute
Address [2] 295529 0
Riddet Institute
Massey University
Private Bag 11 222
Palmerston North 4442
Country [2] 295529 0
New Zealand
Primary sponsor type
University
Name
University of Otago
Address
Po Box 56
Dunedin 9010 Otago
Country
New Zealand
Secondary sponsor category [1] 294596 0
None
Name [1] 294596 0
None
Address [1] 294596 0
None
Country [1] 294596 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296832 0
Health and Disability Ethics Committee
Ethics committee address [1] 296832 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 296832 0
New Zealand
Date submitted for ethics approval [1] 296832 0
07/03/2017
Approval date [1] 296832 0
20/03/2017
Ethics approval number [1] 296832 0
17/STH/41

Summary
Brief summary
There is almost universal acceptance that appropriate nutrition is a pivotal component of attempts to reduce the burden of disease such as obesity, diabetes, cardiovascular disease and some cancers. Healthy eating also has the potential to help achieve equity of health outcomes amongst population groups where inequalities exist such as Maori and Pacific people in New Zealand. While some dietary advice is generally accepted, there is continuing debate regarding the amount and type of dietary carbohydrate. The project proposed is to better understand the potential health benefits of wholegrain foods.

There is convincing evidence that wholegrain consumption protects against colorectal cancer, type 2 diabetes (T2) and cardiovascular disease. Given the global escalation of rates T2 and the importance of colorectal cancer and CVD it is hardly surprising that substantial increases in whole grains have been recommended worldwide. However, what it is in whole grains or the parameters of their consumption that confer health benefits has not been clearly identified.

Whole grains products are recommended in New Zealand and abroad in dietary guidelines however current definitions make no mention of structure and particle size, referring only to grain constituents. Given that an increasing number of relatively refined wholegrain products (as presently defined) are now appearing on supermarket shelves, the potential effect of reducing wholegrain particle size must be considered. It seems possible, indeed likely, that so-called wholegrain foods consumed today may be very different from those available several decades ago in the prospective studies where the benefit of whole grains were clearly demonstrated.

The most recent evidence of the importance of wholegrain particle size on metabolic markers comes from a study by Jarvi et al (1999). Their objective was to compare the effects of diets high in carbohydrate foods that were either minimal processed or highly refined in people with T2. Macronutrient composition and type and amount of dietary fibre were identical. After 24 days, measures of glucose and insulin were 30% lower after the diet of more intact whole grains. LDL cholesterol was also lower. No further research on this topic has been published since, despite it being urgently required.

The immediate objectives of the proposed research are:

(1) to develop a range of wholegrain products with various particle sizes produced under a range of typical food processing conditions and test their acceptability;

(2) to examine the acute physiological effects after ingestion of wholegrain test products in healthy subjects and those diagnosed with T2.

This research will determine the effects of processing these wholegrain products and to inform, if indicated, a change in the definition. This research has the potential to enhance nutrition guidelines in terms of reducing the risk of non-communicable diseases in New Zealand and internationally.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 72166 0
Dr Lisa Te Morenga
Address 72166 0
University of Otago
Department of Human Nutrition
PO Box 56
Dunedin Otago 9010
Country 72166 0
New Zealand
Phone 72166 0
+64210427283
Fax 72166 0
Email 72166 0
lisa.temorenga@otago.ac.nz
Contact person for public queries
Name 72167 0
Dr Lisa Te Morenga
Address 72167 0
University of Otago
Department of Human Nutrition
PO Box 56
Dunedin Otago 9010
Country 72167 0
New Zealand
Phone 72167 0
+64210427283
Fax 72167 0
Email 72167 0
lisa.temorenga@otago.ac.nz
Contact person for scientific queries
Name 72168 0
Dr Lisa Te Morenga
Address 72168 0
University of Otago
Department of Human Nutrition
PO Box 56
Dunedin Otago 9010
Country 72168 0
New Zealand
Phone 72168 0
+64210427283
Fax 72168 0
Email 72168 0
lisa.temorenga@otago.ac.nz

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary