Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000218897
Ethics application status
Approved
Date submitted
27/01/2021
Date registered
3/03/2021
Date last updated
28/04/2024
Date data sharing statement initially provided
3/03/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of intraduodenal administration of quinine on appetite, energy intake and gut hormone release, in response to a standardized buffet-style meal, in humans with type 2 diabetes.
Scientific title
Effects of intraduodenal administration of quinine on appetite, energy intake and gut hormone release, in response to a standardized buffet-style meal, in humans with type 2 diabetes.
Secondary ID [1] 303136 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes
 320244 0
Condition category
Condition code
Metabolic and Endocrine 318177 318177 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will receive in randomised, double-blind fashion, a 10-ml bolus of either (i) 600 mg quinine or (ii) 300 mg quinine, or (iii) water (control) intraduodenally on 3 separate visits. Each visit will be ~4-4.5 hours in duration, and separated by 3-7 days. Visits will be carried out at the Clinical Research Facility, Adelaide Medical School, University of Adelaide, by staff and students trained in the required clinical research techniques.

Participants will consume a standardised dinner meal, (400g McCain's beef lasagne), the night before each study visit by no later than 7pm. After fasting for 13.5 hours overnight and refraining from alcohol and exercise for 24 hours, participants will arrive at the Clinical Research Facility by 8:30am. Upon arrival, participants will be given a standardised light breakfast (1 slice (30 g) whole meal bread, 10 g jam and a cup (200 ml) black tea; ~100 kcal), after which they will be intubated with a 17-channel manometric catheter (Dentsleeve, Mui Scientific) that will be inserted through an anaesthetised nostril and allowed to pass through the stomach and into the duodenum by peristalsis. The infusion port will be positioned ~ 14 cm distal to the pylorus. The correct positioning of the catheter will be monitored continuously by measurement of the transmucosal potential difference in the stomach (~ -40 mV) and the duodenum (~ 0 mV). Once the catheter has been positioned correctly, an intravenous cannula will be placed into a forearm vein for regular blood sampling. At 11.30 am, t = -31 min, a baseline blood sample (10 ml) will be taken, the participant will complete a VAS to assess appetite-related perceptions and GI symptoms as well as the Leeds Food Preference Questionnaire (LFPQ), which is a computerised behavioural task that provides measures of 'liking' and 'wanting' components of food preference and food reward. Immediately thereafter (t = -31 min), participants will receive either (i) 600 mg quinine, (ii) 300 mg quinine, or (iii) water into the duodenum. The adherence or fidelity to the intervention will be assessed or monitored by direct supervision of a research officer who will not be involved in data analysis. 10-ml blood samples for the measurement of plasma concentrations of hormones and glucose will be collected every 10 min (-20, -10, 0), and participants complete VAS questionnaires. At t = 0 min, participants will complete LFPQ and then be presented with a cold, buffet-style meal. Participants will be allowed 30 min to freely consume the meal until comfortably full. Immediately after the meal (t = 30 min) and then every 30 min (t = 60 and 90 min), blood samples will be collected and participants complete VAS questionnaires. At t = 90 min, the intravenous cannula will be removed and participants will be allowed to leave the laboratory.
Intervention code [1] 319436 0
Treatment: Other
Comparator / control treatment
Water
Control group
Placebo

Outcomes
Primary outcome [1] 326165 0
Energy intake at the buffet meal measured using the computer software program FoodWorks.
Timepoint [1] 326165 0
A buffet meal will be presented during each study visit (t = 0-30 min), The subject will be allowed to freely consume food until comfortably full for 30 min. At 30 minutes after consumption of the meal commences, the energy intake at the buffet meal will be measured.
Secondary outcome [1] 390310 0
Plasma concentrations of cholecystokinin, and other gastrointestinal hormones (e.g. PYY, ghrelin), 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 [1] 390310 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] 390313 0
Hunger sensation will be measured using a 100mm Visual Analogue Scale (VAS) questionnaire.
Timepoint [2] 390313 0
Hunger sensation will be measured 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 [3] 390315 0
The desire to eat will be measured using a 100mm Visual Analogue Scale (VAS) questionnaire.
Timepoint [3] 390315 0
The desire to eat will be measured 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 [4] 390316 0
The amount of food the subject thinks he/she could eat ("prospective consumption") will be measured using a 100mm Visual Analogue Scale (VAS) questionnaire.
Timepoint [4] 390316 0
Prospective consumption will be measured 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 [5] 390979 0
Fullness sensation will be measured using a 100mm Visual Analogue Scale (VAS) questionnaire.
Timepoint [5] 390979 0
Fullness sensation will be measured 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 [6] 390980 0
The 'liking' and 'wanting' components of food preference and food reward will be measured using the Leeds Food Preference Questionnaire (LFPQ). This is a composite secondary outcome.
Timepoint [6] 390980 0
The 'liking' and 'wanting' components of food preference and food reward will be measured at t = -31 and 0 min, where t = -31 is just prior to the time of quinine administration and t = 0 is just prior to the start of the buffet meal.
Secondary outcome [7] 392259 0
Blood glucose will be assessed using a hospital grade portable glucmometer.
Timepoint [7] 392259 0
Blood glucose 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.

Eligibility
Key inclusion criteria
Male participants with type 2 diabetes mellitus (T2DM), (aged 18-70 years BMI, 28-37 kg/m2, waist circumference: <102 cm), will be included in the study. T2DM diagnosis will be based on WHO criteria. HbA1c will be >=6.5 - <=7.9% at screening. Blood glucose medications will be required to be withheld for 48 hours prior to each study day. All participants will be required to be weight-stable (ie <5% fluctuation) at study entry, which will be ascertained by a stable body weight in the preceding 4 weeks.
Minimum age
18 Years
Maximum age
70 Years
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Significant gastrointestinal symptoms, disease or surgery;
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.);
Lactose intolerance/other food allergy(ies);
Current gallbladder or pancreatic disease;
Cardiovascular or respiratory diseases;
Individuals with low ferritin levels (females less than 15 ng/mL, males less than 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 not explicitly listed above);
High performance athletes;
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;
Vegetarians;
Inability to comprehend study protocol;
HbA1c <6.5% or >7.9%;
Any patient whose medication cannot be withheld for 48 hours for medical reasons;
Estimated glomerular filtration rate <45 ml/min.

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 allocation schedule, who will be "off-site", to inform her of participant details and study dates. The unblinded study assistant will be, therefore, responsible for allocating a random treatment to the participant and making and administrating 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

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
8/03/2021
Actual
8/03/2021
Date of last participant enrolment
Anticipated
1/11/2023
Actual
17/11/2023
Date of last data collection
Anticipated
30/11/2023
Actual
13/12/2023
Sample size
Target
12
Accrual to date
Final
12
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 307540 0
Government body
Name [1] 307540 0
National Health and Medical Research Council (NHMRC)
Country [1] 307540 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] 308224 0
Individual
Name [1] 308224 0
Professor Michael Horowitz
Address [1] 308224 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] 308224 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307606 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 307606 0
Ethics committee country [1] 307606 0
Australia
Date submitted for ethics approval [1] 307606 0
24/11/2020
Approval date [1] 307606 0
26/11/2020
Ethics approval number [1] 307606 0
CALHN Protocol No. R20161005 HREC/16/RAH/410

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

Contacts
Principal investigator
Name 107838 0
Prof Christine Feinle-Bisset
Address 107838 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 107838 0
Australia
Phone 107838 0
+61 8 8313 6053
Fax 107838 0
Email 107838 0
[email protected]
Contact person for public queries
Name 107839 0
Christine Feinle-Bisset
Address 107839 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 107839 0
Australia
Phone 107839 0
+61 8 8313 6053
Fax 107839 0
Email 107839 0
[email protected]
Contact person for scientific queries
Name 107840 0
Christine Feinle-Bisset
Address 107840 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 107840 0
Australia
Phone 107840 0
+61 8 8313 6053
Fax 107840 0
Email 107840 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
No additional documents have been identified.