We are experiencing 4 week turn-around time in review of submissions and resubmissions. We recommend commencing this process concurrently with your ethics submission and allowing at least 8 weeks for registration to be completed from date of first submission. We currently do not have the capacity to expedite reviews.

Note also there are delays to review of updates. We appreciate your patience.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12620001139965
Ethics application status
Approved
Date submitted
17/09/2020
Date registered
2/11/2020
Date last updated
2/11/2020
Date data sharing statement initially provided
2/11/2020
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 healthy females.
Scientific title
Effects of intraduodenal administration of quinine on blood glucose concentrations, gastric emptying, gut and gluco-regulatory hormone release, and gastrointestinal symptoms in healthy females.
Secondary ID [1] 302233 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes 318941 0
Obesity 318942 0
Healthy human gastrointestinal physiology 318943 0
Condition category
Condition code
Diet and Nutrition 316911 316911 0 0
Obesity
Oral and Gastrointestinal 316912 316912 0 0
Normal oral and gastrointestinal development and function
Metabolic and Endocrine 316913 316913 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. Visits will be scheduled during the follicular phase of the menstrual cycle (i.e., days 1-13) to minimise any potential effects of GI function. 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). 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 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, 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. 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] 318524 0
Treatment: Other
Comparator / control treatment
Water
Control group
Placebo

Outcomes
Primary outcome [1] 325019 0
Blood glucose concentrations before and after quinine or control administration, and following the mixed nutrient drink.
Timepoint [1] 325019 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] 386556 0
Gastric emptying (measurement of 13CO2 in breath samples and by measuring antral area with 2D Ultrasound).
Timepoint [1] 386556 0
Breath samples will be collected and 2D Ultrasound measurements 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] 386558 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] 386558 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] 386560 0
Gastrointestinal symptoms (nausea, bloating) will be measured using a 100mm Visual Analogue Scale (VAS) questionnaire. This is a composite outcome.
Timepoint [3] 386560 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
Healthy
Lean weight (BMI 19-25 kg/m2)
Minimum age
18 Years
Maximum age
55 Years
Gender
Females
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, bodyweight or appetite (eg domperidone and cisapride, anticholinergic drugs (eg atropine), metoclopramide, erythromycin, hyoscine, orlistat, green tea extracts, Astragalus, St Johns Wort etc.);
Take hormonal contraceptive or have an irregular menstrual cycle;
Be pregnant or breastfeeding;
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 will be, therefore, responsible for allocating a random treatment to the participant and making 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
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 306654 0
Government body
Name [1] 306654 0
National Health and Medical Research Council (NHMRC)
Address [1] 306654 0
National Health and Medical Research Council GPO Box 1421 Canberra ACT 2601
Country [1] 306654 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] 307205 0
Individual
Name [1] 307205 0
Professor Michael Horowitz
Address [1] 307205 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] 307205 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306836 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 306836 0
L3, Roma Mitchell Building,
136 North Terrace
Adelaide, SA 5000
Ethics committee country [1] 306836 0
Australia
Date submitted for ethics approval [1] 306836 0
18/05/2020
Approval date [1] 306836 0
21/05/2020
Ethics approval number [1] 306836 0
CALHN Protocol No. R20161005 HREC/16/RAH/410

Summary
Brief summary
The purpose of this trial is to investigate the dose-related effects of intraduodenal administration of the bitter tastant, quinine, which contains no calories, on gastric emptying, gut and gluco-regulatory hormones, postprandial blood glucose and gastrointestinal symptoms in healthy female participants.

We have found previously that specific dietary nutrients, when given into the small intestine in small amounts (and so not contributing significantly to overall energy intake) have the unique ability to substantially stimulate gastrointestinal functions leading to marked improvements in postprandial blood glucose. Some bitter substances also have these effects. Moreover, it has been reported that the response to bitter substances may be more pronounced in women than in men. Therefore, this study will investigate the dose-related responses to quinine in female Volunteers.


Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 105182 0
Prof Christine Feinle-Bisset
Address 105182 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 105182 0
Australia
Phone 105182 0
+61 8 8313 6053
Fax 105182 0
Email 105182 0
christine.feinle@adelaide.edu.au
Contact person for public queries
Name 105183 0
Prof Christine Feinle-Bisset
Address 105183 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 105183 0
Australia
Phone 105183 0
+61 8 8313 6053
Fax 105183 0
Email 105183 0
christine.feinle@adelaide.edu.au
Contact person for scientific queries
Name 105184 0
Prof Christine Feinle-Bisset
Address 105184 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 105184 0
Australia
Phone 105184 0
+61 8 8313 6053
Fax 105184 0
Email 105184 0
christine.feinle@adelaide.edu.au

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 other documents available
Summary results
No Results