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Trial registered on ANZCTR


Registration number
ACTRN12618000814279
Ethics application status
Approved
Date submitted
10/05/2018
Date registered
11/05/2018
Date last updated
20/08/2019
Date data sharing statement initially provided
20/08/2019
Date results information initially provided
20/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of intragastric administration of quinine (bitter agonist), on appetite and gut hormone release in healthy, lean volunteers.
Scientific title
Effects of intragastric administration of quinine (bitter agonist), on appetite and energy intake, and gut hormone release, in healthy, lean volunteers.
Secondary ID [1] 294764 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obesity 307663 0
Type 2 Diabetes 307664 0
Healthy human gastrointestinal physiology 307665 0
Condition category
Condition code
Diet and Nutrition 306729 306729 0 0
Obesity
Oral and Gastrointestinal 306730 306730 0 0
Normal oral and gastrointestinal development and function
Metabolic and Endocrine 306731 306731 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This trial aims to assess the effects of an intragastric administration of quinine on appetite and energy intake.

In this study, subjects will receive, in randomized, double-blind fashion, an intragastric bolus infusion (21 mL) of i) 275 mg quinine; ii) 600 mg quinine and iii) saline (control) followed 30 min later by an ad libitum buffet style meal. Subjects will receive one infusion per study visit. Study visits will be separated by 3-7 days.

For each study visit a baseline blood sample, and Visual analogue Scale (VAS) questionnaire will be collected (t = -31) . The infusion will then be administered using a feeding tube, at the end of which will be marked as t=-30. At t = -20, -10, and 0 min, a further blood sample will be collected and VAS completed. At t = 0 min, subjects will be presented with a cold, buffet-style meal. Subjects will be allowed 30 minutes to freely consume the buffet meal until comfortably full. At t = 30, 60 and 90 min further blood samples will be taken, and VAS administered at t = 30, 45 60, 75 and 90 min,
Intervention code [1] 301067 0
Treatment: Other
Comparator / control treatment
Saline control for within group comparison.
Control group
Placebo

Outcomes
Primary outcome [1] 305723 0
Energy intake at the buffet meal measured using the computer software program FoodWorks.
Timepoint [1] 305723 0
A buffet meal will be presented during each study visit (t = 0-30). The subject will be allowed to freely consume food until comfortably full for 30 minutes.
Secondary outcome [1] 346281 0
Plasma concentrations of cholecystokinin, and other gastrointestinal hormones (e.g. PYY, ghrelin), This outcome is of an exploratory nature so that other gastrointestinal hormones to be measured may be decided upon based on the effect of the intervention on this and other outcomes.
Timepoint [1] 346281 0
Gut hormone release will be assessed from blood samples taken at t = -31, -20, -10, 0, 30, 60 and 90 min, where t = -31 is just prior to the time of quinine administration and t = 0 is the start of the buffet meal.
Secondary outcome [2] 346282 0
Measure satiety sensation using a VAS questionnaire.
Timepoint [2] 346282 0
Satiety will be measured at t = -31, -20, -10, 0, 30, 45, 60, 75 and 90 min, where t = -31 is just prior to the time of quinine administration and t = 0 is the start of the buffet meal.
Secondary outcome [3] 346746 0
Measure hunger sensation using a VAS questionnaire.
Timepoint [3] 346746 0
Hunger will be measured at t = -31, -20, -10, 0, 30, 45, 60, 75 and 90 min, where t = -31 is just prior to the time of quinine administration and t = 0 is the start of the buffet meal.
Secondary outcome [4] 346747 0
Measure fullness sensation using a VAS questionnaire.
Timepoint [4] 346747 0
Fullness will be measured at t = -31, -20, -10, 0, 30, 45, 60, 75 and 90 min, where t = -31 is just prior to the time of quinine administration and t = 0 is the start of the buffet meal.
Secondary outcome [5] 346748 0
Measure the desire to eat using a VAS questionnaire.
Timepoint [5] 346748 0
The desire to eat will be measured at t = -31, -20, -10, 0, 30, 45, 60, 75 and 90 min, where t = -31 is just prior to the time of quinine administration and t = 0 is the start of the buffet meal.
Secondary outcome [6] 346749 0
Measure the amount of food the subject thinks he/she could eat using a VAS questionnaire.
Timepoint [6] 346749 0
The amount of food the subject thinks he/she could eat will be measured at t = -31, -20, -10, 0, 30, 45, 60, 75 and 90 min, where t = -31 is just prior to the time of quinine administration and t = 0 is the start of the buffet meal.

Eligibility
Key inclusion criteria
A total of 12 healthy, lean (BMI 19-25 kg/m2) male subjects, aged between 18 - 55 years, will be included in each study part.
Minimum age
18 Years
Maximum age
55 Years
Gender
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
Significant gastrointestinal symptoms, disease or surgery;
Current gallbladder or pancreatic disease;
Cardiovascular or respiratory diseases;
Any other illnesses as assessed by the investigator (including chronic illnesses not explicitly listed above);
Use of prescribed or non-prescribed medications (including vitamins and herbal supplements) which may affect energy metabolism, gastrointestinal function, body weight or appetite (eg domperidone and cisapride, anticholinergic drugs (eg atropine), metoclopramide, erythromycin, hyoscine, orlistat, green tea extracts, Astragalus, St Johns Wort etc.);
Individuals with low ferritin levels (less than 30 ng/mL), or who have donated blood in the 12 weeks prior to taking part in the study;
Lactose intolerance/other food allergy(ies);
Vegetarians;
Restrained eaters (score >12 on the three factor eating questionnaire).
Current intake of greater than 2 standard drinks on greater than 5 days per week;
Current smokers of cigarettes/cigars/marijuana;
Current intake of any illicit substance;
High performance athletes;
Inability to comprehend study protocol;
Unable to tolerate naso-gastric tube;

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)
Eligible volunteers are assigned a subject number and randomised treatment for each study visit. Randomisation involves contacting the holder (study assistant) of the randomisation table to inform them of subjects details and study dates. The unblinded study assistant is therefore responsible for allocationg a random treatment to the subject and preparing the solution on each study day.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation is generated using a randomization plan generator available at www.randomization.com
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
Not Applicable
Type of endpoint(s)
Pharmacokinetics / pharmacodynamics
Statistical methods / 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 in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 299368 0
Government body
Name [1] 299368 0
NHMRC
Address [1] 299368 0
National Health and Medical Research Council
GPO Box 1421
Canberra
ACT 2601
Country [1] 299368 0
Australia
Primary sponsor type
Individual
Name
Christine Feinle-Bisset
Address
Discipline of Medicine
University of Adelaide
Level 5 Adelaide Health and Medical Sciences Building,
Cnr George St and North Tce,
Adelaide, SA 5005
Country
Australia
Secondary sponsor category [1] 298647 0
Individual
Name [1] 298647 0
Michael Horowitz
Address [1] 298647 0
Discipline of Medicine
University of Adelaide
Level 5 Adelaide Health and Medical Sciences Building,
Cnr George St and North Tce,
Adelaide, SA 5005
Country [1] 298647 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300273 0
Royal Adelaide Hospital Human Research Ethics Committee
Ethics committee address [1] 300273 0
Level 3, Roma Mitchell Building
136 North Terrace
Adelaide SA 5000
Ethics committee country [1] 300273 0
Australia
Date submitted for ethics approval [1] 300273 0
04/10/2016
Approval date [1] 300273 0
15/11/2016
Ethics approval number [1] 300273 0
RAH Protocol No. R20161005 HREC/16/RAH/410

Summary
Brief summary
The purpose of this trial is to investigate the dose-related effects of intragastric administration of the bitter agonist, quinine, a non-nutritive (calorie-free) compound, on energy intake at a subsequent ad libitum buffet style meal, plasma gut hormone concentrations, and appetite perceptions.. The relationship between outcomes and the ability to detect bitter in the oral cavity will also be investigated.
We have found previously that specific dietary nutrients, when given into the small intestine in small amounts (and so not contributing significantly to overall energy intake) have the unique ability to substantially stimulate gastrointestinal functions leading to marked energy intake suppression and improvements in postprandial blood glucose. There has been a recent interest in the effects of bitter compounds, some of which also occur in the diet, including thio-urea compounds in certain vegetables or fruit, or quinine in tonic water, with reported effects on gut functions and energy intake suppression.
This study aims to characterise the dose-related effects of quinine, when delivered intragastrically, in an effort to identify an optimal dose for beneficial effect on the outcomes mentioned herein. This may then guide future research to evaluate hypotheses that observed effects may be further enhanced by combining nutrients with quinine
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 83114 0
Prof Christine Feinle-Bisset
Address 83114 0
Discipline of Medicine
University of Adelaide
Level 5 Adelaide Health and Medical Sciences Building,
Cnr George St and North Tce,
Adelaide, SA 5005
Country 83114 0
Australia
Phone 83114 0
+61 8 8313 6053
Fax 83114 0
Email 83114 0
christine.feinle@adelaide.edu.au
Contact person for public queries
Name 83115 0
Prof Christine Feinle-Bisset
Address 83115 0
Discipline of Medicine
University of Adelaide
Level 5 Adelaide Health and Medical Sciences Building,
Cnr George St and North Tce,
Adelaide, SA 5005
Country 83115 0
Australia
Phone 83115 0
+61 8 8313 6053
Fax 83115 0
Email 83115 0
christine.feinle@adelaide.edu.au
Contact person for scientific queries
Name 83116 0
Prof Christine Feinle-Bisset
Address 83116 0
Discipline of Medicine
University of Adelaide
Level 5 Adelaide Health and Medical Sciences Building,
Cnr George St and North Tce,
Adelaide, SA 5005
Country 83116 0
Australia
Phone 83116 0
+61 8 8313 6053
Fax 83116 0
Email 83116 0
christine.feinle@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
The datasets generated during and/or analysed during the current study are not publicly available due to the ethical statement and informed consent that require privacy of data.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary
In healthy men, intragastric administration of quinine, at the administered doses, did not affect energy intake, appetite perceptions or gastrointestinal symptoms. Based on these outcomes, we decided not to measure gastrointestinal hormones.