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Trial registered on ANZCTR


Registration number
ACTRN12619000707167
Ethics application status
Approved
Date submitted
7/05/2019
Date registered
10/05/2019
Date last updated
16/09/2019
Date data sharing statement initially provided
10/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of intraduodenal versus intragastric administration of quinine on gut function in healthy, lean volunteers.
Scientific title
Effects of intraduodenal versus intragastric administration of quinine on gut and gluco-regulatory hormone release, antropyloroduodenal motility, blood glucose concentrations and appetite perceptions, in healthy, lean volunteers.
Secondary ID [1] 297798 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obesity 312155 0
Type 2 Diabetes 312156 0
Healthy human gastrointestinal physiology 312157 0
Condition category
Condition code
Diet and Nutrition 310700 310700 0 0
Obesity
Oral and Gastrointestinal 310701 310701 0 0
Normal oral and gastrointestinal development and function
Metabolic and Endocrine 310702 310702 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Subjects will receive in randomised, double-blind fashion, a 600mg bolus administration of quinine either intraduodenally or intragastrically on 2 separate visits. Each visit will last 5hrs in duration, and will be separated by 3-7 days. Visits will be carried out in the Adelaide Medical School, University of Adelaide, by staff members trained in the required clinical research facilities.

Subjects will consume a standardised dinner meal, a 400g McCain's beef lasagne, the night before both study visits by no later than 7pm. After fasting for 14 hours overnight and refraining from alcohol and exercise for 24 hours, subjects will arrive at the clinical research facility by 8:30am. Upon arrival, subjects 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 (t=-10 - 0 min), a 9 ml venous blood sample (baseline) will be taken, and the subject will complete a 100mm visual analogue scale questionnaire (VAS) to assess appetite-related perceptions (fullness, hunger, etc.) and GI symptoms (nausea and bloating). At t = -1 min, either the intraduodenal or intragastric bolus of quinine will be administered and another blood sample and VAS questionnaire will be taken immediately after administration. Regular 9ml venous blood samples will be taken throughout the study and additional VAS completed. A total of 90ml of blood will be taken on each study day (180ml over both study visits).
Intervention code [1] 314037 0
Treatment: Other
Comparator / control treatment
Intragastric administration of 600mg bolus of quinine
Control group
Active

Outcomes
Primary outcome [1] 319553 0
Plasma concentrations of gluco-regulatory and gut hormones (Insulin, GLP-1, CCK, glucagon, ghrelin, PYY).
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 [1] 319553 0
Samples will be collected at t = -10, 0 , 10, 20 , 30 , 45, 60 , 75 , 90, 120 min, where t = -10 is prior to quinine administration and t = 0 is immediately post-administartion.
Primary outcome [2] 319725 0
Antropyloroduodenal motility (number of antral, duodenal and isolated pyloric pressure waves, and basal pyloric pressure) will be measured using a 17-channel manometric assembly (Dentsleeve, Mui Scientific).
This outcome is of an exploratory nature so that specific motility 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] 319725 0
Baseline (t = -10 - 0) and after administration (t = 0 -120).
Secondary outcome [1] 368652 0
Blood glucose concentrations.
Timepoint [1] 368652 0
Samples will be collected at t = -10, 0 , 10, 20 , 30 , 45, 60 , 75 , 90, 120 min.
Secondary outcome [2] 368654 0
Measure satiety using a 100mm visual analogue scale questionnaire.
Timepoint [2] 368654 0
Data will be collected at t = -10, 0, 10, 20, 30 ,45, 60, 75, 90, 105, 120 min.
Secondary outcome [3] 370231 0
Measure hunger using a 100mm visual analogue scale questionnaire.
Timepoint [3] 370231 0
Data will be collected at t = -10, 0, 10, 20, 30 ,45, 60, 75, 90, 105, 120 min.
Secondary outcome [4] 370232 0
Measure fullness using a 100mm visual analogue scale questionnaire.
Timepoint [4] 370232 0
Data will be collected at t = -10, 0, 10, 20, 30 ,45, 60, 75, 90, 105, 120 min.
Secondary outcome [5] 370233 0
Measure desire to eat using a 100mm visual analogue scale questionnaire.
Timepoint [5] 370233 0
Data will be collected at t = -10, 0, 10, 20, 30 ,45, 60, 75, 90, 105, 120 min.
Secondary outcome [6] 370234 0
Measure the amount of food the subjects thinks they can eat to eat using a 100mm visual analogue scale questionnaire.
Timepoint [6] 370234 0
Data will be collected at t = -10, 0, 10, 20, 30 ,45, 60, 75, 90, 105, 120 min.
Secondary outcome [7] 370304 0
Measure nausea using a 100mm visual analogue scale questionnaire.
Timepoint [7] 370304 0
Data will be collected at t = -10, 0, 10, 20, 30 ,45, 60, 75, 90, 105, 120 min.
Secondary outcome [8] 370305 0
Measure bloating using a 100mm visual analogue scale questionnaire.
Timepoint [8] 370305 0
Data will be collected at t = -10, 0, 10, 20, 30 ,45, 60, 75, 90, 105, 120 min.

Eligibility
Key inclusion criteria
Healthy
Lean weight (BMI 19-25 kg/m2)
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and 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, 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 subject number and randomised treatment for each study visit. Randomisation involves contacting the holder (study assistant) of the randomisation table to inform them of subject details and study dates. The unblinded study assistant is, therefore, responsible for allocating a random treatment to the subject 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 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 subject 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
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] 302322 0
Government body
Name [1] 302322 0
NHMRC
Address [1] 302322 0
National Health and Medical Research Council
GPO Box 1421
Canberra
ACT 2601
Country [1] 302322 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] 302203 0
Individual
Name [1] 302203 0
Michael Horowitz
Address [1] 302203 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] 302203 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302995 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 302995 0
Level 3, Roma Mitchell Building
136 North Terrace
Adelaide SA 5000
Ethics committee country [1] 302995 0
Australia
Date submitted for ethics approval [1] 302995 0
04/10/2016
Approval date [1] 302995 0
15/11/2016
Ethics approval number [1] 302995 0
CALHN Protocol No. R20161005 HREC/16/RAH/410

Summary
Brief summary
The purpose of this trial is to determine the comparative effects of intraduodenal versus intragastric bolus administration of quinine on gut and gluco-regulatory hormones, antropyloroduodenal motility, blood glucose and appetite responses.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 92110 0
Prof Christine Feinle-Bisset
Address 92110 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 92110 0
Australia
Phone 92110 0
+61 8 8313 6053
Fax 92110 0
Email 92110 0
christine.feinle@adelaide.edu.au
Contact person for public queries
Name 92111 0
Prof Christine Feinle-Bisset
Address 92111 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 92111 0
Australia
Phone 92111 0
+61 8 8313 6053
Fax 92111 0
Email 92111 0
christine.feinle@adelaide.edu.au
Contact person for scientific queries
Name 92112 0
Prof Christine Feinle-Bisset
Address 92112 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 92112 0
Australia
Phone 92112 0
+61 8 8313 6053
Fax 92112 0
Email 92112 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