Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000735752
Ethics application status
Approved
Date submitted
11/05/2022
Date registered
23/05/2022
Date last updated
14/01/2024
Date data sharing statement initially provided
23/05/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
The effects of the bitter agonist, quinine, on gastric emptying in healthy normal-weight volunteers.
Scientific title
The effects of the bitter agonist, quinine, on gastric emptying in healthy normal-weight volunteers.
Secondary ID [1] 306936 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obesity 326045 0
Type 2 diabetes 326046 0
Condition category
Condition code
Diet and Nutrition 323353 323353 0 0
Obesity
Metabolic and Endocrine 323683 323683 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Each participant will be studied on 3 separate occasions, in a double-blind, randomised fashion. Study days will be separated by at least 3-7 days. A standardised dinner meal (beef lasagne, McCain Foods Pty Ltd, Victoria, Australia; 2472 kJ), to be consumed by 7 pm on the night before the study, will be provided to participants on each occasion. Participants will be asked to refrain from any other foods and liquids (except water) until the following morning (~13.5 hours). Water may be consumed until 7 am the morning of the study visit. Participants will be instructed to refrain from exercise and alcohol for 24 hours prior to each study day.

On each study day, the participant will attend the Clinical Research Facility, Adelaide Medical School, Adelaide Health and Medical Sciences (AHMS) Building, at 8.30 am. Upon arrival, an intravenous cannula will be placed into a right forearm vein for regular blood sampling. The participant will then be intubated with a custom-built nasogastric, soft, silicon feeding tube (outer diameter: 4 mm; Dentsleeve, Mississauga, Ontario, Canada) that will be inserted through an anaesthetised nostril and placed in the stomach. Once the catheter has been positioned, the participant will receive, at t=-60 min, either (i) 600 mg or (ii) 300 mg quinine-HCl (Sinkona Indonesia Lestari, Subang, West Java, Indonesia), in 10 ml water, or (iii) water (negative control), into the stomach (to bypass influences from smell and taste of the solution), after which time the tube will be removed immediately. The treatments will be administered by a research officer who will have no involvement in data analysis. 60 min later, at t=-5 min, participant will be provided with a standardised solid-liquid meal to be consumed within 5 min. To do this, the participant will move to the Gamma Camera Suite and be seated with their back against the gamma camera. The meal will consist of 100 g minced beef burger (270 kcal, 25 g protein, 21 g fat), radiolabelled with 10 MBq 99mTc-sulphur colloid, and 150 ml dextrose (10 %, 62 kcal), radiolabelled with 4 MBq 67Ga-EDTA. The liquid will also include 3 g 3-O-methyl-glucose (3-OMG) for the measurement of glucose absorption using plasma samples. Gastric emptying and intragastric distribution of the solid and liquid components of the meal will be measured scintigraphically in 1-min frames for the first 60 min, followed by 3-min frames until t = 120 min, where t = 0 min represents the time of meal completion. At the end of one of the study days, the participant will drink 100 ml water labelled with 4 MBq of 99mTc-sulphur colloid, and a lateral image of the stomach will be acquired to derive correction factors for gamma ray attenuation. Venous blood samples (10 ml) for the measurement of plasma concentrations of gut and glucoregulatory hormones, glucose and 3-OMG will be taken, and the participant will complete visual analogue scale (VAS) questionnaires to assess GI symptoms (nausea and bloating) and appetite-related perceptions (fullness, hunger, desire to eat and prospective food consumption) at regular intervals (12 sampling time points in total, including t=-60, -40, -20, -5, 10, 20, 30, 45, 60, 75, 90, 120 min) throughout the study. VAS questionnaires consist of horizontal 100-mm lines, on which the participant places vertical marks across each line, indicating the strength of each sensation felt at that time, with 0 mm indicating that the sensation is not felt and 100 mm that it is extremely strong. At the end of the study, the intravenous cannula will be removed, and the participant will be offered a light lunch and then be free to leave the laboratory.
Intervention code [1] 323379 0
Treatment: Other
Comparator / control treatment
10 ml distilled water
Control group
Placebo

Outcomes
Primary outcome [1] 331089 0
Plasma glucose concentrations before and after quinine or control administration, and following the test meal.
Timepoint [1] 331089 0
Blood glucose will be assessed from venous blood samples taken at baseline (t=-60 min), in response to quinine or control (t= -40, -20, and -5 min), and then at regular time points for 2 hours following the solid-liquid meal (t= 10, 20, 30, 45, 60, 75, 90, and 120 min).
Secondary outcome [1] 408716 0
Gastric emptying of the meal will be measured scintigraphically, as assessed by 50% emptying time (T50%) for the liquid component and retention of the solid component at 100 min (T100min). This is a composite outcome.
Timepoint [1] 408716 0
Gastric emptying measurement will be recorded in 1-min frames for the first 60 min, followed by 3-min frames until t = 120 min, where t = 0 min represents the time of meal completion. Gastric emptying curves will be used to derive 50% emptying time (T50%) of the liquid component occurring between 0 to 120 min and the solid retention at 100 min.
Secondary outcome [2] 408717 0
Plasma concentrations of gluco-regulatory and gut hormones (e.g. insulin, glucagon, GLP-1) and 3-OMG before and after quinine or control administration, and following the test meal. This outcome is of an exploratory nature so that the specific parameters to be measured may be decided upon based on the effect of the intervention on this and other outcomes, therefore, this is a composite outcome.
Timepoint [2] 408717 0
Plasma concentrations of gluco-regulatory hormones and 3-OMG will be assessed from venous blood samples taken at baseline (t=-60 min), in response to quinine or control (t= -40, -20, and -5 min), and then at regular time points for 2 hours following the solid-liquid meal (t= 10, 20, 30, 45, 60, 75, 90, and 120 min).
Secondary outcome [3] 408718 0
Gastrointestinal symptoms (nausea, bloating) and appetite-related perceptions (fullness, hunger, desire to eat and prospective food consumption) will be measured using a 100mm Visual Analogue Scale (VAS) questionnaire. This is a composite outcome.
Timepoint [3] 408718 0
Gastrointestinal symptoms and appetite-related perceptions (fullness, hunger, desire to eat and prospective food consumption) will be assessed at baseline (t=-60 min), in response to quinine or control (t= -40, -20, and -5 min), and then at regular time points for 2 hours following the solid-liquid meal (t= 10, 20, 30, 45, 60, 75, 90, and 120 min).

Eligibility
Key inclusion criteria
Healthy normal-weight (BMI: 19-25 kg/m2)
Minimum age
40 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
-regular gastrointestinal symptoms, as measured by the gastrointestinal symptom score (score >1 for any component) or significant gastrointestinal disease
-previous gastrointestinal surgery (other than gallbladder removal)
-use of prescribed or non-prescribed medications (including vitamins and herbal supplements) which may affect energy metabolism, gastrointestinal function, body weight or appetite (e.g. domperidone, anticholinergic drugs (e.g. atropine), metoclopramide, erythromycin, hyoscine, orlistat, green tea extracts, Astragalus, St Johns Wort etc.)
-substantial daily consumption of quinine, e.g. as part of quinine-based anti-malaria treatment (irregular consumption of small amounts of quinine, e.g. in tonic water, is acceptable)
-regular medication that may affect any of the study outcomes (i.e. gastrointestinal motor or hormone function) and cannot be discontinued during the study
-other food allergy
-current gallbladder or pancreatic disease
-coagulation abnormalities
-oesophageal varices or strictures
-cardiovascular or respiratory diseases that may affect any of the study outcomes and/or tolerance of the naso-duodenal tube
-all types of epilepsy
-individuals with low ferritin levels (females <15 ng/mL, males <30 ng/mL), or who have donated blood in the 12 weeks prior to taking part in the study
-any other illnesses as assessed by the investigator (including chronic illnesses that may affect any of the study outcomes and not explicitly listed above)
-exposure to ionising radiation from X-ray machines or radioactive substances in the last 12 months for research purposes
-high performance athletes, due to their specific dietary requirements and energy intakes (i.e. much higher than the average population), which affect gastrointestinal functions
-current intake of > 2 standard alcoholic drinks on > 5 days per week, due to the known effects of alcohol on gastrointestinal function
-current smokers/users of tobacco products (including pipe, chewing, cigarettes, cigars, sheesha, vaping)
-recreational drug use (e.g. marijuana)
-current intake of any illicit substance (since all of these, i.e. tobacco products, marijuana and illicit drugs may affect gastrointestinal functions)
-vegetarians
-inability to tolerate oro/naso-gastric tube
-inability to comprehend study protocol
-in premenopausal females, pregnancy, lactation or surgical sterilisation (a pregnancy test will be performed, using a urine sample, on the morning of study day);
-female participants with irregular period cycles, since studies will be performed during the follicular phase, to avoid any influences of the different stages of the menstrual cycle on study outcomes.

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 participant number and randomised treatment for each study visit. Randomisation involves contacting the holder (study assistant) of the randomisation table to inform them of participant details and study dates. The unblinded study assistant will be, therefore, responsible for allocating a random treatment to the participant and preparing that on the study days.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation is generated using a randomisation 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
Pharmacodynamics
Statistical methods / analysis
All data will be encrypted to ensure participant details remain confidential. Statistical analysis will be performed in collaboration with a biostatistician. Glucose and hormone concentrations, gastric emptying, and gastrointestinal symptoms will be analysed using repeated-measures analysis of variance (ANOVA), with time and treatment as factors. Post-hoc paired comparisons, corrected for multiple comparisons, will be performed if ANOVAs reveal significant effects.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/06/2022
Actual
27/05/2022
Date of last participant enrolment
Anticipated
1/11/2024
Actual
Date of last data collection
Anticipated
18/12/2024
Actual
Sample size
Target
14
Accrual to date
9
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 311253 0
Government body
Name [1] 311253 0
National Health and Medical Research Council (NHMRC)
Country [1] 311253 0
Australia
Primary sponsor type
Individual
Name
Professor Christine Feinle-Bisset
Address
Adelaide Medical School
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] 312611 0
Individual
Name [1] 312611 0
Professor Michael Horowitz
Address [1] 312611 0
Adelaide Medical School
University of Adelaide
Level 6 Adelaide Health and Medical Sciences Building
Cnr George St and North Tce
Adelaide, SA 5005
Country [1] 312611 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310767 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 310767 0
Ethics committee country [1] 310767 0
Australia
Date submitted for ethics approval [1] 310767 0
Approval date [1] 310767 0
13/09/2021
Ethics approval number [1] 310767 0

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

Contacts
Principal investigator
Name 118790 0
Prof Christine Feinle-Bisset
Address 118790 0
Adelaide Medical School
Faculty of Health and Medical Sciences
University of Adelaide
Level 5 Adelaide Health and Medical Sciences Building
Cnr George St and North Tce
Adelaide, SA 5005
Country 118790 0
Australia
Phone 118790 0
+61 8 8313 6053
Fax 118790 0
Email 118790 0
[email protected]
Contact person for public queries
Name 118791 0
Christine Feinle-Bisset
Address 118791 0
Adelaide Medical School
Faculty of Health and Medical Sciences
University of Adelaide
Level 5 Adelaide Health and Medical Sciences Building
Cnr George St and North Tce
Adelaide, SA 5005
Country 118791 0
Australia
Phone 118791 0
+61 8 8313 6053
Fax 118791 0
Email 118791 0
[email protected]
Contact person for scientific queries
Name 118792 0
Christine Feinle-Bisset
Address 118792 0
Adelaide Medical School
Faculty of Health and Medical Sciences
University of Adelaide
Level 5 Adelaide Health and Medical Sciences Building
Cnr George St and North Tce
Adelaide, SA 5005
Country 118792 0
Australia
Phone 118792 0
+61 8 8313 6053
Fax 118792 0
+61 8 8313 6053
Email 118792 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


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.