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Trial registered on ANZCTR


Registration number
ACTRN12619000420145
Ethics application status
Approved
Date submitted
15/02/2019
Date registered
14/03/2019
Date last updated
6/05/2019
Date data sharing statement initially provided
14/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The impact of age on the effects of whey protein intake on blood glucose, insulin and gut mechanisms.
Scientific title
The impact of age on the acute effects of whey protein intake on blood glucose, plasma insulin concentrations and underlying gut mechanisms in younger and older type 2 diabetes patients.
Secondary ID [1] 297245 0
None
Universal Trial Number (UTN)
U1111-1227-6787
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes 311321 0
Condition category
Condition code
Metabolic and Endocrine 309962 309962 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The proposed project consists of a randomized, double-blind, placebo-controlled, within-participants design. It aims to determine the acute effects of drinks containing either :
(i) 30g whey protein (120 kcal, 120 ml), (ii) 30g glucose (120 kcal, 120 ml), (iii) 30g glucose plus 30g whey protein (240 kcal, 120 ml), (iv) iso-palatable flavoured control drink (~2 kcal, 120 ml). All drinks will have a similar look, smell and taste. Participants will be studied during 4 study days and drinks will be randomised over the study days. Both the participants and the investigators analysing the data will be blinded to the treatment allocation.

Participants will attend the laboratory for a screening visit after reading the volunteer information sheet and after after signing the consent form a total of 20 older (aged 65 years or more) and 20 younger (aged 18 - 50 years) people with type 2 diabetes (managed by diet and/or metformin), and 40, age-, gender- and body-weight-matched, healthy controls, will be recruited. Each subject will be studied on 4 occasions. On each occasion, they will receive, in randomized fashion, any of the flavoured drinks as mentioned above. Participants will arrive at the laboratory ~8.00 am after fasting for ~12 hours overnight and refraining from exercise and alcohol for ~24 hours. Participants will be required to similar meal of their own choice the night before each study day and refrain from consuming anything other than water after 7pm. Upon arrival, an intravenous catheter will be inserted for blood sampling. Blood samples (~15 mL) will be collected at regular intervals (before the drink (0 mins) and 15, 30, 60, 90, 120, 180 min after ingestion of the drink), blood pressure and heart rate. 180 min after ingestion of the study drink, participants will be presented, with a standard, cold, buffet-style meal. A visual analogue scale (VAS) questionnaire to assess perceptions of appetite and gastrointestinal symptoms will be given.
The wash out period would be 5 days in order to eliminate the effects of the drink, if any.

Our PhD student will administer the drinks face to face individually and do the measurements at the Adelaide Health and Medical Sciences building.
Intervention code [1] 313499 0
Prevention
Comparator / control treatment
Control drink with distilled water and cordial
Control group
Placebo

Outcomes
Primary outcome [1] 318871 0
blood glucose using a Yellow Springs Instrument analyser






Timepoint [1] 318871 0
AUC glucose concentration based on blood collection at (before the drink (0 mins) and 15, 30, 60, 90, 120, 180 min after ingestion of the drink)
Primary outcome [2] 318872 0
blood insulin concentrations-Plasma insulin concentrations (milliunits per liter) will be determined by enzyme-linked immunosorbent assay (ELISA).
Homeostatic model assessment index (HOMA-IR) will be calculated (insulin concentration (microunits per liter) x glucose concentration (nanomoles per liter) / 22.5).
Timepoint [2] 318872 0
AUC insulin concentration based on blood collection at (before the drink (0 mins) and 15, 30, 60, 90, 120, 180 min after ingestion of the drink)
Secondary outcome [1] 366294 0
Gastric emptying using a 13C-Octanoic acid breath test.
Timepoint [1] 366294 0
This breath test assesses gastric emptying of the drink through measurement of 13CO2 in the breath via mass spectrometry. It is based on Area under curve and half emptying time for measurements done at (before the drink (0 mins) and 15, 30, 60, 90, 120, 180 min after ingestion of the drink)
Secondary outcome [2] 366652 0
Blood pressure is determined using an automatic sphygmomanometer.


Timepoint [2] 366652 0
Blood pressure is measured at (before the drink (0 mins) and 15, 30, 60, 90, 120, 180 min after ingestion of the drink)
Secondary outcome [3] 366653 0
Gastrointestinal symptoms using a Visual Analog Scale (VAS) (bloating, nausea)
Timepoint [3] 366653 0
VAS is administered at time points: (before the drink (0 mins) and 15, 30, 60, 90, 120, 180 min after ingestion of the drink)
Secondary outcome [4] 368177 0
Heart rate is determined using an automatic sphygmomanometer.
Timepoint [4] 368177 0
Heart rate is measured at (before the drink (0 mins) and 15, 30, 60, 90, 120, 180 min after ingestion of the drink)
Secondary outcome [5] 368178 0
Plasma GLP-1 concentrations
Timepoint [5] 368178 0
AUC GLP-1 hormone concentration based blood samples will be taken at (before the drink (0 mins) and 15, 30, 60, 90, 120, 180 min after ingestion of the drink)
Secondary outcome [6] 368179 0
Plasma GIP concentrations
Timepoint [6] 368179 0
AUC GIP hormone concentration based blood samples will be taken at (before the drink (0 mins) and 15, 30, 60, 90, 120, 180 min after ingestion of the drink)
Secondary outcome [7] 368180 0
Plasma glucagon concentrations
Timepoint [7] 368180 0
AUC Glucagon concentration based blood samples will be taken at (before the drink (0 mins) and 15, 30, 60, 90, 120, 180 min after ingestion of the drink)

Eligibility
Key inclusion criteria
Inclusion criteria include male and female adults with a BMI of 22 kg/m2 or more. Patients with type 2 diabetes will have a HbA1c greater than or equal to 6.5% and less than or equal to 7.9% at the time of screening.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Each subject will be questioned prior to the study to exclude:
• smokers of cigarettes/cigars/marijuana;
• intake of > 20 g alcohol on a daily basis;
• vegetarians;
• intake of any illicit substance;
• requirement for insulin or other diabetes medications, other than metformin;
• significant gastrointestinal symptoms, or history of gastrointestinal disease including known gastroparesis, or surgery (other than appendectomy or cholecystectomy), proteinuria;
• current use of medications which are likely to affect gastrointestinal function or appetite (e.g. opiates, anticholinergics, levodopa, calcium-channel antagonists, beta blockers, clonidine, nitrates, tricyclic antidepressants, selective serotonin re-uptake inhibitors, phosphodiesterase type 5 inhibitors, sumatriptan, metoclopramide, domperidone, cisapride, tegaserod, or erythromycin);
• for women current pregnancy or lactation;
• use of non-prescribed medications (including vitamins and herbal supplements) which may affect appetite, body weight, gastrointestinal function or energy metabolism (e.g. green tea extracts, Astragalus, St Johns Wort etc.);
• any other illness deemed significant by the investigator (including chronic illnesses not explicitly listed above);
• individuals who are found to be unable to comprehend the study protocol.

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)
Central randomisation by computer. The study has a within subjects design - all participants receive all interventions in randomised order. Consenting eligible subjects will be enrolled and subject details will be entered into a study spreadsheet kept on a password-secured and backed-up server. The subjects will be assigned to the next available Subject ID from the appropriate treatment allocation schedule which will specify the randomised order that the subject will complete the four treatments.The allocation is blinded to the participant and the researcher who performs the screening and who decides whether a subject is eligible to participate. The conditions will be coded by a researcher who is not involved in the acquiring the data.'
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation schedules will be generated at randomization.com using balanced permutations in a single block. This will specify a random order of treatments for each subject. Separate randomisation schedules will be generated for the groups.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Crossover
Other design features
mixed between-within subjects design
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Sample size calculations have been, and data will be, analysed by a biostatistician.
The study has a mixed between-within participants design in which samples of participants are studied under different conditions. Sample size requirements are based on statistical power functions of between-groups contrasts of (i) older versus younger and (ii) patients with type 2 versus controls, each with overall P=0.05, statistical power of 0.8 and anticipated drop-out rate of ~10%, and significance levels adjusted to account for the 4 comparisons (whey protein, glucose, whey protein plus glucose, control). Calculations have been performed for the primary outcome of area under the curve of glucose, assuming a within-subject SD of 0.5 mmol/l, and a between-participants SD of 1.4 mmol/l to detect a difference between groups of 1.5 mmol/l, and between treatments of 0.4 mmol/l

Recruitment
Recruitment status
Not yet recruiting
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 in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 13018 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 25504 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 301806 0
Charities/Societies/Foundations
Name [1] 301806 0
Diabetes Australia
Address [1] 301806 0
Diabetes SA
Postal Address:
GPO Box 1930
Adelaide SA 5001

Office Location:
159 Sir Donald Bradman Drive
Hilton South Australia 5033
Country [1] 301806 0
Australia
Primary sponsor type
Individual
Name
Dr. Stijn Soenen
Address
Central Adelaide Local Health Network, Adelaide Medical School and Centre of Research in Translation Nutritional Science to good Health, Adelaide Medical School., AHMS, Cnr Norh Terrace and George Street, Adelaide, SA 5000
Country
Australia
Secondary sponsor category [1] 301549 0
None
Name [1] 301549 0
none
Address [1] 301549 0
none
Country [1] 301549 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302512 0
Central Adelaide Local Health Network HREC
Ethics committee address [1] 302512 0
Central Adelaide Local Health Network,Level 3, Roma Mitchell House,North Terrace, Adelaide SA,Australia 5000
Ethics committee country [1] 302512 0
Australia
Date submitted for ethics approval [1] 302512 0
Approval date [1] 302512 0
04/08/2018
Ethics approval number [1] 302512 0

Summary
Brief summary
We hypothesise that whey protein slows gastric emptying, stimulates “incretin” hormones and insulin secretion, and reduces glycaemia; that age and type 2 diabetes will modify these responses. The study aims to determine the acute effects of drinks containing either (i) whey protein, (ii) glucose, (iii) whey protein plus glucose, or (iv) control on blood gucose, insulin and gut hormones. A total of 20 older and 20 younger people with type 2 diabetesand 40 healthy controls, will be recruited. Blood samples, Gastric emptying, blood pressure, heart rate etc will be measured after taking informed consent.
Completion of the study will provide us with useful data on gastric emptying of carbohydrates, protein and a combination of these nutrients, and on the effects of these nutrients on energy intake. This will give us novel and important information which can be translated to the community to improve overall health in older people.
Trial website
Trial related presentations / publications
Public notes
Subjects will be provided with an information sheet, and written, informed consent will be obtained prior to their inclusion. All proposed methods to be used are safe and have been extensively used in previous studies performed within the department.

Contacts
Principal investigator
Name 90470 0
Dr Stijn Soenen
Address 90470 0
Central Adelaide Local Health Network, Adelaide Medical School & Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, the University of Adelaide, AHMS Cnr North Terrace and George Street, Adelaide, SA, 5000.
Country 90470 0
Australia
Phone 90470 0
+61 0487333418
Fax 90470 0
Email 90470 0
stijn.soenen@adelaide.edu.au
Contact person for public queries
Name 90471 0
Prof Ian Chapman
Address 90471 0
Senior Specialist Endocrinologist, Discipline of Medicine & Centre of Research Excellence in Translation Nutritional Science to Good Health, Adelaide Medical School, University of Adelaide, Royal Adelaide Hospital, North Terrace Adelaide, SA 5000
Country 90471 0
Australia
Phone 90471 0
+61 413561085
Fax 90471 0
Email 90471 0
ian.chapman@adelaide.edu.au
Contact person for scientific queries
Name 90472 0
Prof Ian Chapman
Address 90472 0
Senior Specialist Endocrinologist, Discipline of Medicine & Centre of Research Excellence in Translation Nutritional Science to Good Health, Adelaide Medical School, University of Adelaide, Royal Adelaide Hospital, North Terrace Adelaide, SA 5000
Country 90472 0
Australia
Phone 90472 0
+61 8 8222 4162
Fax 90472 0
Email 90472 0
ian.chapman@adelaide.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Study protocol
Statistical analysis plan
Informed consent form
Clinical study report
Ethical approval
Summary results
No Results