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Trial registered on ANZCTR


Registration number
ACTRN12618001764224
Ethics application status
Approved
Date submitted
23/10/2018
Date registered
26/10/2018
Date last updated
26/10/2018
Date data sharing statement initially provided
26/10/2018
Date results information initially provided
26/10/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Does stimulation of gastrointestinal bitter taste receptors reduce energy intake and improve postprandial glycaemia in type 2 diabetes?
Scientific title
Does stimulation of gastrointestinal bitter taste receptors reduce energy intake and improve postprandial glycaemia in type 2 diabetes?
Secondary ID [1] 294803 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes mellitus 307722 0
Obesity 307723 0
Condition category
Condition code
Diet and Nutrition 306777 306777 0 0
Obesity
Metabolic and Endocrine 306778 306778 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Following a screening visit, each subject will be studied on 4 occasions including 2 experimental settings: Parts A and B, 2 conditions each, separated by at least 7 days, in a double-blinded randomised order.
On each study day, a cannula will be inserted in an antecubital vein for regular blood sampling. Subjects will then consume a gelatin capsule containing either 30 mg denatonium benzoate (DB) or 30 mg sodium chloride (control) with 150 mL water (we will monitor adherence to the intervention by mouth check). 30 min after taking the capsule, they will have a standardised test meal comprising 65 g powdered potato and 20 g glucose reconstituted with 200 mL water labelled with 100 mg 13C-octanoic acid for evaluation of gastric emptying and postprandial glycaemia (Part A: the first two of the 4 visits), or a standardised ad libitum buffet meal for evaluation of energy intake (Part B: the last two of the 4 visits).
Intervention code [1] 301109 0
Treatment: Other
Intervention code [2] 312748 0
Treatment: Drugs
Comparator / control treatment
Control: 30 mg sodium chloride.
Control group
Placebo

Outcomes
Primary outcome [1] 305768 0
differences in the incremental area under the curve (iAUC) for plasma glucose after DB compared with control (Part A).
Timepoint [1] 305768 0
at t = -30, 0, 30, 60, 90, 120, 150, 180, 210 and 240min where t=-30 is when capsule is given and t=0 is when mash potato meal is served.
Primary outcome [2] 305769 0
differences in energy intake from a standardised cold buffet meal after DB compared with control (Part B). Energy intake is quantified using commercial software (Foodworks, Australia).
Timepoint [2] 305769 0
t=30 where t=0 is when the buffet meal is served.
Secondary outcome [1] 346442 0
differences in gastric emptying (T50) after DB compared with control (Part A). Gastric emptying is measured by the breath test. 13CO2 in each breath sample was measured by a non-dispersive infrared spectrometer (FANci2, Fischer ANalysen Instrumente, Germany).
Timepoint [1] 346442 0
at t=0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 75, 90, 105, 120, 135, 150, 165, 180, 195, 210, 225, 240 min where t=0 is when mash potato meal is served.
Secondary outcome [2] 346444 0
differences in the incremental area under the curve (iAUC) for plasma GLP-1 after DB compared with control (Part A).
Timepoint [2] 346444 0
at t = -30, 0, 30, 60, 90, 120, 150, 180, 210 and 240min where t=-30 is when capsule is given (Part A).
Secondary outcome [3] 346445 0
differences in the incremental area under the curve (iAUC) for plasma peptide YY (PYY) after DB compared with control (Part A).
Timepoint [3] 346445 0
at t = -30, 0, 30, 60, 90, 120, 150, 180, 210 and 240min where t=-30 is when capsule is given.
Secondary outcome [4] 346446 0
differences in the incremental area under the curve (iAUC) for plasma cholecystokinin (CCK) after DB compared with control (Part A).
Timepoint [4] 346446 0
at t = -30, 0, 30, 60, 90, 120, 150, 180, 210 and 240min where t=-30 is when capsule is given.
Secondary outcome [5] 346447 0
differences in the incremental area under the curve (iAUC) for plasma ghrelin after DB compared with control (Part A).
Timepoint [5] 346447 0
at t = -30, 0, 30, 60, 90, 120, 150, 180, 210 and 240min where t=-30 is when capsule is given.
Secondary outcome [6] 346448 0
differences in the incremental area under the curve (iAUC) for plasma insulin after DB compared with control (Part A).
Timepoint [6] 346448 0
at t = -30, 0, 30, 60, 90, 120, 150, 180, 210 and 240min where t=-30 is when capsule is given.
Secondary outcome [7] 346449 0
differences in the incremental area under the curve (iAUC) for plasma glucagon after DB compared with control (Part A).
Timepoint [7] 346449 0
at t = -30, 0, 30, 60, 90, 120, 150, 180, 210 and 240min where t=-30 is when capsule is given.

Eligibility
Key inclusion criteria
Type 2 diabetes (World Health Organisation (WHO) criteria), managed by diet or metformin only
Body mass index (BMI) from 20 to 40 kg/m2
Age from 50 to 75 years
Males and post-menopausal females
Glycated haemoglobin (HbA1c) equal to 8.5%
Haemoglobin above the lower limit of the normal range (ie. greater than 135g/L for men and 115g/L for women), and ferritin above the lower limit of normal (ie. more than 30ng/mL for men and greater than 20mg/mL for women)
Minimum age
50 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Use of any medication that may influence gastrointestinal motor function within 48 hours or 5 half-lives of the study, specifically: opiates, anticholinergics, levodopa, beta-blockers, clonidine, nitrates, phosphodiesterase type 5 inhibitors, sumatriptan, metoclopramide, domperidone, cisapride, tegaserod, or erythromycin
Evidence of drug abuse, or consumption of more than 20 g alcohol or 10 cigarettes on a daily basis
History of gastrointestinal disease, including significant upper or lower gastrointestinal symptoms, pancreatitis, or previous gastrointestinal surgery (other than uncomplicated appendicectomy or cholecystectomy)
Other significant illness, including epilepsy, cardiovascular or respiratory disease
Impaired renal or liver function (as assessed by calculated creatinine clearance less than 90 mL/min or abnormal liver function tests (more than 2 times upper limit of normal range))
Donation of blood within the previous 3 months
Participation in any other research studies within the previous 3 months
Females who are pre-menopausal
Inability to give informed consent
Participants who do not eat beef
Vegetarian diet

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
sealed opaque envelopes
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
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Efficacy
Statistical methods / analysis
Based on data derived from our previous study, 14 healthy subjects will provide 80% power (at a=0.05) to detect (i) a 30% reduction in the iAUC0-4h for plasma glucose after the standardized test meal (Part A) and (ii) a 25% reduction in energy intake at the buffet meal (Part B), after 30 mg DB versus control. 16 subjects will be recruited to the study to allow dropouts.
Data will be analysed using standardised, non-parametric or parametric statistical methods where appropriate (e.g. repeated measures ANOVA).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
9/10/2017
Date of last participant enrolment
Anticipated
Actual
1/02/2018
Date of last data collection
Anticipated
Actual
8/03/2018
Sample size
Target
16
Accrual to date
Final
16
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 10843 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 22587 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 299402 0
Government body
Name [1] 299402 0
NHMRC
Country [1] 299402 0
Australia
Primary sponsor type
University
Name
University of Adelaide
Address
Level 5 Adelaide Health and Medical Sciences (AHMS) Building, North Terrace
Adelaide SA 5000
Country
Australia
Secondary sponsor category [1] 298688 0
None
Name [1] 298688 0
Address [1] 298688 0
Country [1] 298688 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300305 0
Royal Adelaide Hospital Human Research Ethics Committee
Ethics committee address [1] 300305 0
Level 4, Women's Health Centre, Royal Adelaide Hospital, North Terrace, Adelaide, SA 5000
Ethics committee country [1] 300305 0
Australia
Date submitted for ethics approval [1] 300305 0
24/11/2016
Approval date [1] 300305 0
18/12/2016
Ethics approval number [1] 300305 0
No: R20161129 HREC/16/RAH/498

Summary
Brief summary
Emerging evidence of preclinical studies suggests that bitter substances in the gut can reduce appetite and slow the emptying of meals from the stomach, by stimulating gut hormone release. The proposed project will evaluate the hypotheses that, in patients with T2DM, activation of gastrointestinal bitter taste receptors(BTRs) substantially slows gastric emptying and reduces postprandial glycaemia after a standardized meal (Part A), and suppresses energy intake at an ad libitum buffet meal (Part B), in association with augmented secretion of glucagon-like peptide-1 (GLP-1)), peptide YY (PYY), cholecystokinin (CCK) and insulin, and suppression of ghrelin and glucagon. We will stimulate BTRs, as previously, using denatonium benzoate, the most potent BTR agonist known, to which humans are reproducibly sensitive.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 83226 0
Dr Tongzhi Wu
Address 83226 0
University of Adelaide Discipline of Medicine, Level 5 Adelaide Health and Medical Sciences (AHMS) Building, North Terrace, Adelaide, SA 5000
Country 83226 0
Australia
Phone 83226 0
+61 8 8313 6535
Fax 83226 0
Email 83226 0
tongzhi.wu@adelaide.edu.au
Contact person for public queries
Name 83227 0
Tongzhi Wu
Address 83227 0
University of Adelaide Discipline of Medicine, Level 5 Adelaide Health and Medical Sciences (AHMS) Building, North Terrace, Adelaide, SA 5000
Country 83227 0
Australia
Phone 83227 0
+61 8 8313 6535
Fax 83227 0
Email 83227 0
tongzhi.wu@adelaide.edu.au
Contact person for scientific queries
Name 83228 0
Tongzhi Wu
Address 83228 0
University of Adelaide Discipline of Medicine, Level 5 Adelaide Health and Medical Sciences (AHMS) Building, North Terrace, Adelaide, SA 5000
Country 83228 0
Australia
Phone 83228 0
+61 8 8313 6535
Fax 83228 0
Email 83228 0
tongzhi.wu@adelaide.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


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.