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Trial registered on ANZCTR


Registration number
ACTRN12616000026426
Ethics application status
Approved
Date submitted
6/01/2016
Date registered
15/01/2016
Date last updated
25/11/2019
Date data sharing statement initially provided
25/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of the bitter taste chemical, denatonium benzoate, on metabolic control in healthy adults.
Scientific title
Effect of bitter taste chemical, denatonium benzoate, on glycaemia, gastrointestinal hormones, antropyloroduodenal motility and appetite in healthy adults.
Secondary ID [1] 288249 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
type 2 diabetes 297179 0
Condition category
Condition code
Metabolic and Endocrine 297397 297397 0 0
Normal metabolism and endocrine development and function
Metabolic and Endocrine 297474 297474 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Following enrolment, each subject will be studied on three occasions, separated by at least 7 days, in a double-blind, randomized fashion. On each study day, following correct positioning of the intraduodenal catheter, intraduodenal infusion of (i) low dose (10 mg dissolved in 250 mL water) or (ii) high dose (30 mg dissolved in 250 mL water) of denatonium benzoate or (iii) control (250 mL water only) will be commenced, with 100 mL infused during t = ­-60 to 0 min, and the remaining 150 mL infused over the next 90 min (t = 0 to 90 min). All doses are administered at study site by staff. During the latter period (t = 0 to 90 min), ID glucose will be infused at 2 kcal/min. At the end of infusions, a cold buffet meal will be given for evaluation of energy intake (t = 90-120 min).
Intervention code [1] 293532 0
Treatment: Other
Comparator / control treatment
intraduodenal administration of water was used as the control treatment
Control group
Placebo

Outcomes
Primary outcome [1] 296945 0
differences in the incremental area under the curve (iAUC) for plasma GLP-1 after different doses of denatonium benzoate, compared with control
Timepoint [1] 296945 0
at t = -60, -45, -30, -15, 0, 15, 30, 45, 60, 90 and 120 min, where t = -60 min is start of water or denatonium benzoate infusion, t = 0 min is start of additional intraduodenal glucose infusion at 2 kcal/min, t = 90 min is end of intraduodenal infusions, and t = 120 min is end of buffet meal.
Primary outcome [2] 296946 0
differences in the incremental area under the curve (iAUC) for plasma glucose after different doses of denatonium benzoate, compared with control
Timepoint [2] 296946 0
at t = -60, -45, -30, -15, 0, 15, 30, 45, 60, 90 and 120 min, where t = -60 min is start of water or denatonium benzoate infusion, t = 0 min is start of additional intraduodenal glucose infusion at 2 kcal/min, t = 90 min is end of intraduodenal infusions, and t = 120 min is end of buffet meal.
Primary outcome [3] 296947 0
differences in energy intake (by weighing of food consumed at the buffet meal) after different doses of denatonium benzoate, compared with control
Timepoint [3] 296947 0
during t = 90 and 120 min, where t = 90 min is end of intraduodenal infusions and start of buffet meal, and t = 120 min is end of buffet meal.
Secondary outcome [1] 319746 0
differences in the incremental area under the curve (iAUC) for plasma GIP after different doses of denatonium benzoate, compared with control
Timepoint [1] 319746 0
at t = -60, -45, -30, -15, 0, 15, 30, 45, 60, 90 and 120 min, where t = -60 min is start of water or denatonium benzoate infusion, t = 0 min is start of additional intraduodenal glucose infusion at 2 kcal/min, t = 90 min is end of intraduodenal infusions, and t = 120 min is end of buffet meal.
Secondary outcome [2] 319747 0
differences in the incremental area under the curve (iAUC) for plasma PYY after different doses of denatonium benzoate, compared with control
Timepoint [2] 319747 0
at t = -60, -45, -30, -15, 0, 15, 30, 45, 60, 90 and 120 min, where t = -60 min is start of water or denatonium benzoate infusion, t = 0 min is start of additional intraduodenal glucose infusion at 2 kcal/min, t = 90 min is end of intraduodenal infusions, and t = 120 min is end of buffet meal.
Secondary outcome [3] 319748 0
differences in the incremental area under the curve (iAUC) for plasma CCK after different doses of denatonium benzoate, compared with control
Timepoint [3] 319748 0
at t = -60, -45, -30, -15, 0, 15, 30, 45, 60, 90 and 120 min, where t = -60 min is start of water or denatonium benzoate infusion, t = 0 min is start of additional intraduodenal glucose infusion at 2 kcal/min, t = 90 min is end of intraduodenal infusions, and t = 120 min is end of buffet meal.
Secondary outcome [4] 319749 0
differences in the incremental area under the curve (iAUC) for plasma insulin after different doses of denatonium benzoate, compared with control
Timepoint [4] 319749 0
at t = -60, -45, -30, -15, 0, 15, 30, 45, 60, 90 and 120 min, where t = -60 min is start of water or denatonium benzoate infusion, t = 0 min is start of additional intraduodenal glucose infusion at 2 kcal/min, t = 90 min is end of intraduodenal infusions, and t = 120 min is end of buffet meal.
Secondary outcome [5] 319750 0
differences in the incremental area under the curve (iAUC) for plasma glucagon after different doses of denatonium benzoate, compared with control
Timepoint [5] 319750 0
at t = -60, -45, -30, -15, 0, 15, 30, 45, 60, 90 and 120 min, where t = -60 min is start of water or denatonium benzoate infusion, t = 0 min is start of additional intraduodenal glucose infusion at 2 kcal/min, t = 90 min is end of intraduodenal infusions, and t = 120 min is end of buffet meal.
Secondary outcome [6] 319751 0
differences in the incremental area under the curve (iAUC) for plasma ghrelin after different doses of denatonium benzoate, compared with control
Timepoint [6] 319751 0
at t = -60, -45, -30, -15, 0, 15, 30, 45, 60, 90 and 120 min, where t = -60 min is start of water or denatonium benzoate infusion, t = 0 min is start of additional intraduodenal glucose infusion at 2 kcal/min, t = 90 min is end of intraduodenal infusions, and t = 120 min is end of buffet meal.
Secondary outcome [7] 319752 0
Differences in the number of antropyloroduodenal pressure waves (measured using a manometric assembly which is connected to a computer-based system for recording of the number of pressure waves across the antropyloroduodenal area) after different doses of denatonium benzoate, compared with control.
Timepoint [7] 319752 0
every 15 min during t = -60 to 90 min, where t = -60 min is start of water or denatonium benzoate infusion, t = 0 min is start of additional intraduodenal glucose infusion at 2 kcal/min, and t = 90 min is end of intraduodenal infusions.

Eligibility
Key inclusion criteria
* Healthy male and females aged 18 – 55 years
* Body mass index (BMI) 19 - 25 kg/m2
* Haemoglobin above the lower limit of the normal range (ie. >135g/L for men and 115g/L for women), and ferritin above the lower limit of normal (ie. >30ng/mL for men and >20mg/mL for women)
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
* Use of any medication that may influence gastrointestinal motor function, body weight or appetite (e.g. antihypertensive drugs, domperidone and cisapride, anticholinergic drugs (e.g. atropine), metoclopramide, erythromycin, hyoscine, orlistat, green tea extracts, Astragalus, St. John's Wort etc.)
* Evidence of drug abuse, 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 < 90 mL/min or abnormal liver function tests (> 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
* Inability to give informed consent
* Female participants who are pregnant or planning for pregnancy, or are lactating
* Vegetarians

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
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Based on data derived from previous rodent and human studies, 16 participants will provide at least 80% power (at a = 0.025, to enable correction for including extra comparisons between 10 mg denatonium benzoate and control) to detect (i) a 50% increase in the incremental area under the curve (iAUC) for plasma GLP-1, GIP, PYY and CCK, (ii) a 30% reduction in the iAUC for plasma glucose, and (iii) a 36% reduction in energy intake, after 30 mg denatonium benzoate versus control (water) during ID glucose infusion at a rate of 2 kcal/min. 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
8/02/2016
Actual
1/06/2016
Date of last participant enrolment
Anticipated
11/11/2016
Actual
11/10/2016
Date of last data collection
Anticipated
Actual
11/11/2016
Sample size
Target
16
Accrual to date
Final
16
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 5003 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 12491 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 292627 0
Hospital
Name [1] 292627 0
royal adelaide hospital clinical project grant
Country [1] 292627 0
Australia
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital
Address
Level 6, Eleanor Harrald Building
Royal Adelaide Hospital
North Terrace
Adelaide SA 5000
Country
Australia
Secondary sponsor category [1] 291345 0
None
Name [1] 291345 0
Address [1] 291345 0
Country [1] 291345 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294110 0
Royal Adelaide Hospital Human Research Ethics Committee
Ethics committee address [1] 294110 0
Ethics committee country [1] 294110 0
Australia
Date submitted for ethics approval [1] 294110 0
24/11/2015
Approval date [1] 294110 0
05/01/2016
Ethics approval number [1] 294110 0
HREC/15/RAH/522 R20151165

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 52298 0
Dr Tongzhi Wu
Address 52298 0
Discipline of Medicine, Royal Adelaide Hospital, Level 6, Eleanor Harrald Building, Frome Road, Adelaide, SA, 5000.
Country 52298 0
Australia
Phone 52298 0
+61 8 8222 5038
Fax 52298 0
Email 52298 0
tongzhi.wu@adelaide.edu.au
Contact person for public queries
Name 52299 0
Tongzhi Wu
Address 52299 0
Discipline of Medicine, Royal Adelaide Hospital, Level 6, Eleanor Harrald Building, Frome Road, Adelaide, SA, 5000.
Country 52299 0
Australia
Phone 52299 0
+61 8 8222 5038
Fax 52299 0
Email 52299 0
tongzhi.wu@adelaide.edu.au
Contact person for scientific queries
Name 52300 0
Tongzhi Wu
Address 52300 0
Discipline of Medicine, Royal Adelaide Hospital, Level 6, Eleanor Harrald Building, Frome Road, Adelaide, SA, 5000.
Country 52300 0
Australia
Phone 52300 0
+61 8 8222 5038
Fax 52300 0
Email 52300 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.