ANZCTR - Registration

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]

None

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

type 2 diabetes

Condition category

Condition code

Metabolic and Endocrine

Normal metabolism and endocrine development and function

Metabolic and Endocrine

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]

Treatment: Other

Comparator / control treatment

intraduodenal administration of water was used as the control treatment

Control group

Placebo

Outcomes

Primary outcome [1]

differences in the incremental area under the curve (iAUC) for plasma GLP-1 after different doses of denatonium benzoate, compared with control

Timepoint [1]

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]

differences in the incremental area under the curve (iAUC) for plasma glucose after different doses of denatonium benzoate, compared with control

Timepoint [2]

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]

differences in energy intake (by weighing of food consumed at the buffet meal) after different doses of denatonium benzoate, compared with control

Timepoint [3]

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]

differences in the incremental area under the curve (iAUC) for plasma GIP after different doses of denatonium benzoate, compared with control

Timepoint [1]

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]

differences in the incremental area under the curve (iAUC) for plasma PYY after different doses of denatonium benzoate, compared with control

Timepoint [2]

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]

differences in the incremental area under the curve (iAUC) for plasma CCK after different doses of denatonium benzoate, compared with control

Timepoint [3]

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]

differences in the incremental area under the curve (iAUC) for plasma insulin after different doses of denatonium benzoate, compared with control

Timepoint [4]

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]

differences in the incremental area under the curve (iAUC) for plasma glucagon after different doses of denatonium benzoate, compared with control

Timepoint [5]

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]

differences in the incremental area under the curve (iAUC) for plasma ghrelin after different doses of denatonium benzoate, compared with control

Timepoint [6]

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]

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]

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

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]

The Royal Adelaide Hospital - Adelaide

Recruitment postcode(s) [1]

5000 - Adelaide

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

royal adelaide hospital clinical project grant

Country [1]

Australia

Primary sponsor type

Hospital

Name

Royal Adelaide Hospital

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Royal Adelaide Hospital Human Research Ethics Committee

Ethics committee address [1]

Level 4, Women’s Health Centre Royal Adelaide Hospital North Terrace Adelaide, South Australia, 5000

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

24/11/2015

Approval date [1]

05/01/2016

Ethics approval number [1]

HREC/15/RAH/522 R20151165

Summary

Brief summary

The small intestine is the key interface between ingested food and the human body, particularly given its capacity to “sense” the presence of nutrients in much the same way as the tongue, through activation of similar taste receptors. This taste perception can influence nutrient uptake, as well as the release of gut hormones and neurotransmitters involved in the regulation of gastrointestinal motility, energy intake and blood glucose homeostasis. The purpose of the study is to provide proof of concept that intestinal bitter taste sensing has a favourable effect on metabolic control.

Specifically, the study will evaluate the hypothesis that activation of intestinal bitter taste receptors (by intraduodenal administration of a bitter chemical, denatonium benzoate) augments secretion of gut hormones, thereby increasing insulin, suppressing glucagon and ghrelin, and modulating antropyloroduodenal motility (to slow gastric emptying), with a consequent reduction of the blood glucose response to small intestinal glucose infusion and potentiation of the reduction in energy intake in healthy human participants.

Trial website

Public notes

Contacts

Principal investigator

Name

Dr Tongzhi Wu

Address

Discipline of Medicine, Royal Adelaide Hospital, Level 6, Eleanor Harrald Building, Frome Road, Adelaide, SA, 5000.

Country

Australia

Phone

+61 8 8222 5038

Email

[email protected]

Contact person for public queries

Name

Tongzhi Wu

Address

Discipline of Medicine, Royal Adelaide Hospital, Level 6, Eleanor Harrald Building, Frome Road, Adelaide, SA, 5000.

Country

Australia

Phone

+61 8 8222 5038

Email

[email protected]

Contact person for scientific queries

Name

Tongzhi Wu

Address

Discipline of Medicine, Royal Adelaide Hospital, Level 6, Eleanor Harrald Building, Frome Road, Adelaide, SA, 5000.

Country

Australia

Phone

+61 8 8222 5038

Email

[email protected]

Trial Review

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