Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001269123
Ethics application status
Approved
Date submitted
27/08/2019
Date registered
12/09/2019
Date last updated
3/09/2020
Date data sharing statement initially provided
12/09/2019
Date results provided
3/09/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of intraduodenal versus intragastric administration of quinine on blood glucose and gut function in healthy, lean volunteers.
Scientific title
Effects of intraduodenal versus intragastric administration of quinine on blood glucose concentrations, gastric emptying, gut and gluco-regulatory hormone release, and gastrointestinal symptoms in healthy, lean volunteers.
Secondary ID [1] 299059 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 Diabetes 314083 0
Obesity 314084 0
Healthy human gastrointestinal physiology 314085 0
Condition category
Condition code
Diet and Nutrition 312460 312460 0 0
Obesity
Oral and Gastrointestinal 312461 312461 0 0
Normal oral and gastrointestinal development and function
Metabolic and Endocrine 312462 312462 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will receive in randomised, double-blind fashion, a bolus of either quinine (600mg), or water (total volume: 10mL), either intraduodenally or intragastrically on 4 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 manometric catheter consists of 16 side holes spaced at 1.5 cm intervals, measuring pressures in the antrum, pylorus, and duodenum (APD pressures). The most proximal antral channel (with the side hole positioned approximately 9cm proximal to the pylorus when the catheter is in position) is used for intragastric administration. An additional channel (with the side hole positioned approximately 14 cm distal to the pylorus when the catheter is in position) is used for intraduodenal administration. The correct positioning of the catheter will be maintained by continuous measurement of the transmucosal potential difference (TMPD) between the most distal antral channel and the most proximal duodenal channel. All manometric channels will be perfused with degassed, distilled water, except for the two TMPD channels, which will be perfused with degassed 0.9% saline, at 0.15 ml/min. An intravenous cannula will be placed into a right forearm vein for regular blood sampling to measure plasma hormone concentrations. Once the catheter has been positioned correctly, fasting motility will be monitored continuously, and immediately after the end of phase III activity of the fasting migrating motor complex (MMC), during a period of motor quiescence, an 8 ml venous blood sample (baseline) will be taken, and the subject will complete a 100mm visual analogue scale questionnaire (VAS) to assess GI symptoms (nausea and bloating). Either the intraduodenal (t = -32) or intragastric (t=- 62) bolus of quinine or water will be administered and the manometric catheter was then removed, after which venous blood samples and VAS taken every 10 minutes. 30 min after intraduodenal infusion and 60 min after intragastric infusion, (at t = -1), 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. Regular venous blood samples and VAS will be taken throughout the study and breath samples taken every 5 minutes for the first hour after the drink (t= 0 – 60 min) and every 15 minutes for the second hour (t= 60 – 120 min).
Intervention code [1] 315328 0
Treatment: Other
Comparator / control treatment
Distilled water control, will be both intraduodenally and intragastrically administered on separate study days to act as controls for each location of quinine administration.
Control group
Placebo

Outcomes
Primary outcome [1] 321131 0
Blood glucose concentrations before and after administration, and following the mixed nutrient drink.
Timepoint [1] 321131 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 2 hours following the mixed-nutrient drink.
Secondary outcome [1] 374059 0
Gastric emptying (measurement of 13CO2 in breath samples).
Timepoint [1] 374059 0
Breath samples will be collected once at baseline, and then every 5 minutes for the first hour after the nutrient drink, and every 15 minutes for the second hour after the nutrient drink.
Secondary outcome [2] 374082 0
Update Plasma concentrations of gluco-regulatory and gut hormones (including insulin, glucagon, GLP-1). This outcome is of an exploratory nature so that specific gastrointestinal hormones 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] 374082 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 2 hours following the mixed-nutrient drink (at t = 10, 20, 30, 45, 60, 90 & 120 min).
Secondary outcome [3] 374196 0
Gastrointestinal symptoms (nausea, bloating) will be measured using a 100mm Visual Analogue Scale (VAS). This VAS has been extensively employed in published studies conducted by the investigators. 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 [3] 374196 0
Gastrointestinal symptoms will be assessed from VAS questionnaires, taken at baseline, every 10 minutes in response to quinine or control, and then at regular time points for 2 hours following the mixed-nutrient drink (at t = 10, 20, 30, 45, 60, 90 & 120 min).

Eligibility
Key inclusion criteria
Healthy
Lean weight (BMI 19-25 kg/m2)
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 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 is, therefore, responsible for allocating a random treatment to the participant and administering the dose.
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 professional biostatistician. Hormone concentrations, APD motility, glucose concentrations and appetite perceptions 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 gut hormones and appetite perceptions. 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
23/09/2019
Actual
23/09/2019
Date of last participant enrolment
Anticipated
28/02/2020
Actual
28/02/2020
Date of last data collection
Anticipated
27/03/2020
Actual
27/03/2020
Sample size
Target
14
Accrual to date
Final
14
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 303594 0
Government body
Name [1] 303594 0
NHMRC
Country [1] 303594 0
Australia
Primary sponsor type
Individual
Name
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] 303679 0
Individual
Name [1] 303679 0
Michael Horowitz
Address [1] 303679 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] 303679 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304122 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 304122 0
Ethics committee country [1] 304122 0
Australia
Date submitted for ethics approval [1] 304122 0
04/10/2016
Approval date [1] 304122 0
15/11/2016
Ethics approval number [1] 304122 0
CALHN Protocol No. R20161005 HREC/16/RAH/410

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

Contacts
Principal investigator
Name 95890 0
Prof Christine Feinle-Bisset
Address 95890 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 95890 0
Australia
Phone 95890 0
+61 8 8313 6053
Fax 95890 0
Email 95890 0
[email protected]
Contact person for public queries
Name 95891 0
Christine Feinle-Bisset
Address 95891 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 95891 0
Australia
Phone 95891 0
+61 8 8313 6053
Fax 95891 0
Email 95891 0
[email protected]
Contact person for scientific queries
Name 95892 0
Christine Feinle-Bisset
Address 95892 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 95892 0
Australia
Phone 95892 0
+61 8 8313 6053
Fax 95892 0
Email 95892 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
SourceTitleYear of PublicationDOI
Dimensions AIComparative Effects of Intragastric and Intraduodenal Administration of Quinine on the Plasma Glucose Response to a Mixed-Nutrient Drink in Healthy Men: Relations with Glucoregulatory Hormones and Gastric Emptying2021https://doi.org/10.1093/jn/nxab020
EmbaseEffects of Quinine on the Glycaemic Response to, and Gastric Emptying of, a Mixed-Nutrient Drink in Females and Males.2023https://dx.doi.org/10.3390/nu15163584
N.B. These documents automatically identified may not have been verified by the study sponsor.