Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618000813280
Ethics application status
Approved
Date submitted
10/05/2018
Date registered
11/05/2018
Date last updated
21/08/2019
Date data sharing statement initially provided
21/08/2019
Date results provided
21/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of intragastric administration of quinine on gastric emptying, gut hormone release, blood glucose and appetite sensations, in healthy, lean volunteers.
Scientific title
Effects of intragastric administration of quinine on gastric emptying, gut hormone release, blood glucose and appetite sensations, in healthy, lean volunteers.
Secondary ID [1] 294773 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obesity 307675 0
Type 2 Diabetes 307676 0
Healthy human gastrointestinal physiology 307677 0
Condition category
Condition code
Diet and Nutrition 306743 306743 0 0
Obesity
Oral and Gastrointestinal 306744 306744 0 0
Normal oral and gastrointestinal development and function
Metabolic and Endocrine 306745 306745 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This trial aims to assess the dose-relative effects of intragastric administration of quinine on gastric emptying, gut and gluco-regulatory hormones, postprandial blood glucose, and appetite in response to a mixed-nutrient drink.

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) 30 min before 350 ml (500 kcal) of a mixed-nutrient drink to evaluate the effects on gastric emptying, and the hormone, postprandial blood glucose, and appetite, responses to the mixed-nutrient drink. Study visits will be separated by 3-7 days and subjects will receive one infusion per visit.

For each study visit a baseline blood sample, VAS, and breath sample 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 -1 min further blood samples will be collected and VAS completed.
At t = -1 min, subjects will consume, within 1 minute, a mixed-nutrient drink (Resource Plus, 500 kcal, 350 ml) labeled with 100 mg of 13C-acetate for measurement of gastric emptying by breath sampling, and 3g 3-OMG for measurement of glucose absorption. Blood samples and VAS will be taken every 15 minutes, and breath samples will be taken every 5 min, over the next hour (t = 0 to 60 min). Over the following hour, VAS and blood samples will be collected every half hour (t = 90, 120), and breath samples collected every 15 min (t = 75, 90, 105, 120).
In addition, gastric emptying will be evaluated using 2D ultrasound by measuring antral area at baseline and every 5 min after ingestion of the mixed liquid meal (t=0-30 min) and then at 15-min intervals (t=30-120 min)
Intervention code [1] 301077 0
Treatment: Other
Comparator / control treatment
Saline control for within group comparison.
Control group
Placebo

Outcomes
Primary outcome [1] 305735 0
Blood glucose before and after infusion administration, and following the mixed nutrient drink.
Timepoint [1] 305735 0
Blood glucose will be assessed from blood samples taken at t = -31, -20, -10, -1, 15, 30, 45, 60, 90, 120 min, where t = -31 is just prior to the time of quinine administration and t = -1 is just prior to nutrient drink consumption.
Primary outcome [2] 305736 0
Gastric Emptying (measurement of 13CO2 in breath samples and by measuring antral area with 2D Ultrasound).
Timepoint [2] 305736 0
Breath samples will be collected at t = -31 min, every 5 minutes from t = 0 to 60 min, and every 15 minutes from t = 60 to 120 min.
2D Ultrasound will be performed at baseline and every 5 min after ingestion of the mixed liquid meal (t=0-30 min) and then at 15-min intervals (t=30-120 min)
Secondary outcome [1] 346323 0
Glucose absorption, assessed using 3-OMG, which is added to the nutrient drink.
Timepoint [1] 346323 0
Glucose absorption will be assessed from blood samples taken at t = -31, 15, 30, 45, 60, 90, and 120 min, where t = -31 is just prior to the time of quinine administration and t = 15 is 15 min following ingestion of the nutrient drink.
Secondary outcome [2] 346324 0
Plasma concentrations of gastrointestinal hormones (e.g. GLP-1, GIP).
Timepoint [2] 346324 0
Gut hormone will be assessed from blood samples taken at t = -31, -20, -10, -1, 15, 30, 45, 60, 90, and 120 min, where t = -31 is just prior to the time of quinine administration and t = -1 is just prior to nutrient drink consumption.
Secondary outcome [3] 346750 0
Plasma concentrations of insulin.
Timepoint [3] 346750 0
Insulin concentrations will be assessed from blood samples taken at t = -31, -20, -10, -1, 15, 30, 45, 60, 90, and 120 min, where t = -31 is just prior to the time of quinine administration and t = -1 is just prior to nutrient drink consumption.
Secondary outcome [4] 346751 0
Plasma concentrations of glucagon.
Timepoint [4] 346751 0
Glucagon concentrations will be assessed from blood samples taken at t = -31, -20, -10, -1, 15, 30, 45, 60, 90, and 120 min, where t = -31 is just prior to the time of quinine administration and t = -1 is just prior to nutrient drink consumption.
Secondary outcome [5] 346752 0
Plasma concentrations of glucose.
Timepoint [5] 346752 0
Glucagon concentrations will be assessed from blood samples taken at t = -31, -20, -10, -1, 15, 30, 45, 60, 90, and 120 min, where t = -31 is just prior to the time of quinine administration and t = -1 is just prior to nutrient drink consumption.
Secondary outcome [6] 346753 0
Measure satiety sensation using a VAS questionnaire.
Timepoint [6] 346753 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 [7] 346754 0
Measure hunger sensation using a VAS questionnaire.
Timepoint [7] 346754 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 [8] 346755 0
Measure fullness sensation using a VAS questionnaire.
Timepoint [8] 346755 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 [9] 346756 0
Measure the desire to eat using a VAS questionnaire.
Timepoint [9] 346756 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 [10] 346757 0
Measure the amount of food the subject thinks he/she could eat using a VAS questionnaire.
Timepoint [10] 346757 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 15 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
Sex
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
All data will be encrypted to ensure subject details remain confidential. Statistical analysis will be performed in collaboration with a professional biostatistician. Data relating to gastric emptying, intestinal glucose absorption, glucose and hormone concentrations and appetite profiles will be analysed using repeated-measures analysis of variance (ANOVA), with time and treatment as factors. One-way ANOVA will be used to evaluate AUC data for appetite and gut hormones. Post-hoc paired comparisons, corrected for multiple comparisons, will be performed if ANOVAs reveal significant effects. Relationships between the outcomes will be evaluated using regression analysis. The results will be submitted for publication in a peer-reviewed journal.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
28/05/2018
Actual
28/05/2018
Date of last participant enrolment
Anticipated
5/12/2018
Actual
25/02/2019
Date of last data collection
Anticipated
19/12/2018
Actual
5/03/2019
Sample size
Target
12
Accrual to date
Final
15
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 299378 0
Government body
Name [1] 299378 0
NHMRC
Country [1] 299378 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] 298657 0
Individual
Name [1] 298657 0
Michael Horowitz
Address [1] 298657 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] 298657 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300281 0
Royal Adelaide Hospital Human Research Ethics Committee
Ethics committee address [1] 300281 0
Ethics committee country [1] 300281 0
Australia
Date submitted for ethics approval [1] 300281 0
04/10/2016
Approval date [1] 300281 0
15/11/2016
Ethics approval number [1] 300281 0
RAH Protocol No. R20161005 HREC/16/RAH/410

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

Contacts
Principal investigator
Name 83146 0
Prof Christine Feinle-Bisset
Address 83146 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 83146 0
Australia
Phone 83146 0
+61 8 8313 6053
Fax 83146 0
Email 83146 0
[email protected]
Contact person for public queries
Name 83147 0
Christine Feinle-Bisset
Address 83147 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 83147 0
Australia
Phone 83147 0
+61 8 8313 6053
Fax 83147 0
Email 83147 0
[email protected]
Contact person for scientific queries
Name 83148 0
Christine Feinle-Bisset
Address 83148 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 83148 0
Australia
Phone 83148 0
+61 8 8313 6053
Fax 83148 0
Email 83148 0
[email protected]

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 Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIIntragastric administration of the bitter tastant quinine lowers the glycemic response to a nutrient drink without slowing gastric emptying in healthy men2019https://doi.org/10.1152/ajpregu.00294.2019
N.B. These documents automatically identified may not have been verified by the study sponsor.