Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000972921
Ethics application status
Approved
Date submitted
27/08/2020
Date registered
28/09/2020
Date last updated
8/05/2023
Date data sharing statement initially provided
28/09/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of intraduodenal administration of quinine on blood glucose concentrations, gastric emptying, gut and gluco-regulatory hormone release, and gastrointestinal symptoms in humans with type 2 diabetes.
Scientific title
Effects of intraduodenal administration of quinine on blood glucose concentrations, gastric emptying, gut and gluco-regulatory hormone release, and gastrointestinal symptoms in humans with type 2 diabetes.
Secondary ID [1] 301791 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes 318266 0
Condition category
Condition code
Metabolic and Endocrine 316279 316279 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 ~5hrs 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 14 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 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 to measure plasma hormone concentrations, and a baseline venous blood sample (10 mL) and Visual analogue Scale (VAS) questionnaire, to assess gastrointestinal symptoms (nausea and bloating), will be collected. Immediately thereafter (t = -31 min), participants will receive a 10-ml bolus of either (i) 600 mg quinine or (ii) 300 mg quinine, or (iii) water into the duodenum, after which the catheter will be removed and blood samples and VAS taken every 10 minutes. 30 min later (at t = -1 min), participants will consume, within 1 minute, 350ml (500 kcal) of a mixed-nutrient drink (Resource Plus) labelled with 100mg of 13C-acetate for measurement of gastric emptying by breath sampling and and 3 g 3-O-methyl-glucose (3-OMG) for the measurement of glucose absorption using plasma samples. Further venous blood samples and VAS will be taken every 10 min over the first 30 min after ingestion of the drink (t = 0 – 30 min) and then at 15-min intervals (t = 30 – 60 min), 30-min intervals (t = 60 – 120 min), and at t = 180 min. In addition, gastric emptying will be evaluated using breath test and 2D ultrasound (measuring antral area) at baseline and every 5 min after ingestion of the drink (t = 0 – 60 min) and then at 15-min intervals (t = 60 – 180 min). At t=180 min, after final blood and breath samples, ultrasound and VAS measurements, participants will be served a light lunch, after which they will be allowed to leave the laboratory.
Intervention code [1] 318094 0
Treatment: Other
Comparator / control treatment
Water
Control group
Placebo

Outcomes
Primary outcome [1] 324454 0
Blood glucose concentrations before and after quinine or control administration, and following the mixed nutrient drink.
Timepoint [1] 324454 0
Blood glucose will be assessed from venous blood samples taken at baseline, every 10 minutes in response to quinine or control, and then at regular time points for 3 hours following the mixed-nutrient drink.
Secondary outcome [1] 384710 0
Gastric emptying (measurement of 13CO2 in breath samples and by measuring antral area with 2D Ultrasound).
Timepoint [1] 384710 0
Breath samples will be collected and 2D Ultrasound will be performed at baseline, and then every 5 minutes for the first hour, and every 15 minutes for the next two hours after the mixed-nutrient drink.
Secondary outcome [2] 384711 0
Plasma concentrations of gluco-regulatory and gut hormones (e.g. insulin, glucagon, GLP-1). 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] 384711 0
Plasma hormone concentrations will be assessed from venous blood samples taken at baseline, every 10 minutes in response to quinine or control, and then at regular time points for 3 hours following the mixed-nutrient drink.
Secondary outcome [3] 384712 0
Gastrointestinal symptoms (nausea, bloating) will be measured using a 100mm Visual Analogue Scale (VAS) questionnaire. This is a composite outcome.
Timepoint [3] 384712 0
Gastrointestinal symptoms will be assessed at baseline, every 10 minutes in response to quinine or control, and then at regular time points for 3 hours following the mixed-nutrient drink.

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. T2DM patients will need to be diet-controlled, with or without blood glucose medications (<2 g/d). Blood glucose medications will 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 (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% - >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
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, breath and ultrasound measurements, 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
Completed
Date of first participant enrolment
Anticipated
6/10/2020
Actual
1/10/2020
Date of last participant enrolment
Anticipated
31/07/2022
Actual
11/11/2021
Date of last data collection
Anticipated
19/08/2022
Actual
26/11/2021
Sample size
Target
12
Accrual to date
Final
12
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 306225 0
Government body
Name [1] 306225 0
National Health and Medical Research Council (NHMRC)
Country [1] 306225 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] 306703 0
Individual
Name [1] 306703 0
Professor Michael Horowitz
Address [1] 306703 0
Adelaide Medical School University of Adelaide Level 5 Adelaide Health and Medical Sciences Building, Cnr George St and North Tce, Adelaide, SA 5005
Country [1] 306703 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306436 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 306436 0
Ethics committee country [1] 306436 0
Australia
Date submitted for ethics approval [1] 306436 0
18/05/2020
Approval date [1] 306436 0
21/05/2020
Ethics approval number [1] 306436 0
CALHN Protocol No. R20161005 HREC/16/RAH/410

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

Contacts
Principal investigator
Name 103866 0
Prof Christine Feinle-Bisset
Address 103866 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 103866 0
Australia
Phone 103866 0
+61 8 8313 6053
Fax 103866 0
Email 103866 0
[email protected]
Contact person for public queries
Name 103867 0
Christine Feinle-Bisset
Address 103867 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 103867 0
Australia
Phone 103867 0
+61 8 8313 6053
Fax 103867 0
Email 103867 0
[email protected]
Contact person for scientific queries
Name 103868 0
Christine Feinle-Bisset
Address 103868 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 103868 0
Australia
Phone 103868 0
+61 8 8313 6053
Fax 103868 0
Email 103868 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.