None listed
Conditions
Brief summary
The aim of the study is to assess the effect of a bitter compound, quinine, on gastric emptying and intragastric distribution of a mixed solid-liquid meal, using the ‘gold standard’, scintigraphy, secretion of glucoregulatory hormones and postprandial blood glucose. We have recently established that quinine, when allowed to sufficiently interact with small intestinal bitter receptors, reduces postprandial blood glucose by stimulating glucoregulatory functions, including slowing of gastric emptying and stimulating glucoregulatory hormones. Gastric emptying was measured by 13C-acetate breath test, a non-radioactive, non-invasive test that provides a broad indication of the relative effect on gastric emptying, but does not allow quantification of gastric content over time, or examination of intragastric meal distribution. However, scintigraphy is the ‘gold standard’ for the measurement of both liquid and solid gastric emptying. Moreover, this technique allows quantification of intragastric meal distribution, i.e. both proximal and distal gastric contents.
Interventions
Each participant will be studied on 3 separate occasions, in a double-blind, randomised fashion. Study days will be separated by at least 3-7 days. A standardised dinner meal (beef lasagne, McCain Foods Pty Ltd, Victoria, Australia; 2472 kJ), to be consumed by 7 pm on the night before the study, will be provided to participants on each occasion. Participants will be asked to refrain from any other foods and liquids (except water) until the following morning (~13.5 hours). Water may be consumed u
Each participant will be studied on 3 separate occasions, in a double-blind, randomised fashion. Study days will be separated by at least 3-7 days. A standardised dinner meal (beef lasagne, McCain Foods Pty Ltd, Victoria, Australia; 2472 kJ), to be consumed by 7 pm on the night before the study, will be provided to participants on each occasion. Participants will be asked to refrain from any other foods and liquids (except water) until the following morning (~13.5 hours). Water may be consumed until 7 am the morning of the study visit. Participants will be instructed to refrain from exercise and alcohol for 24 hours prior to each study day. On each study day, the participant will attend the Clinical Research Facility, Adelaide Medical School, Adelaide Health and Medical Sciences (AHMS) Building, at 8.30 am. Upon arrival, an intravenous cannula will be placed into a right forearm vein for regular blood sampling. The participant will then be intubated with a custom-built nasogastric, soft, silicon feeding tube (outer diameter: 4 mm; Dentsleeve, Mississauga, Ontario, Canada) that will be inserted through an anaesthetised nostril and placed in the stomach. Once the catheter has been positioned, the participant will receive, at t=-60 min, either (i) 600 mg or (ii) 300 mg quinine-HCl (Sinkona Indonesia Lestari, Subang, West Java, Indonesia), in 10 ml water, or (iii) water (negative control), into the stomach (to bypass influences from smell and taste of the solution), after which time the tube will be removed immediately. The treatments will be administered by a research officer who will have no involvement in data analysis. 60 min later, at t=-5 min, participant will be provided with a standardised solid-liquid meal to be consumed within 5 min. To do this, the participant will move to the Gamma Camera Suite and be seated with their back against the gamma camera. The meal will consist of 100 g minced beef burger (270 kcal, 25 g protein, 21 g fat), radiolabelled with 10 MBq 99mTc-sulphur colloid, and 150 ml dextrose (10 %, 62 kcal), radiolabelled with 4 MBq 67Ga-EDTA. The liquid will also include 3 g 3-O-methyl-glucose (3-OMG) for the measurement of glucose absorption using plasma samples. Gastric emptying and intragastric distribution of the solid and liquid components of the meal will be measured scintigraphically in 1-min frames for the first 60 min, followed by 3-min frames until t = 120 min, where t = 0 min represents the time of meal completion. At the end of one of the study days, the participant will drink 100 ml water labelled with 4 MBq of 99mTc-sulphur colloid, and a lateral image of the stomach will be acquired to derive correction factors for gamma ray attenuation. Venous blood samples (10 ml) for the measurement of plasma concentrations of gut and glucoregulatory hormones, glucose and 3-OMG will be taken, and the participant will complete visual analogue scale (VAS) questionnaires to assess GI symptoms (nausea and bloating) and appetite-related perceptions (fullness, hunger, desire to eat and prospective food consumption) at regular intervals (12 sampling time points in total, including t=-60, -40, -20, -5, 10, 20, 30, 45, 60, 75, 90, 120 min) throughout the study. VAS questionnaires consist of horizontal 100-mm lines, on which the participant places vertical marks across each line, indicating the strength of each sensation felt at that time, with 0 mm indicating that the sensation is not felt and 100 mm that it is extremely strong. At the end of the study, the intravenous cannula will be removed, and the participant will be offered a light lunch and then be free to leave the laboratory.
Sponsors
Professor Christine Feinle-Bisset
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
40 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy normal-weight (BMI: 19-25 kg/m2)
Exclusion criteria
-regular gastrointestinal symptoms, as measured by the gastrointestinal symptom score (score >1 for any component) or significant gastrointestinal disease -previous gastrointestinal surgery (other than gallbladder removal) -use of prescribed or non-prescribed medications (including vitamins and herbal supplements) which may affect energy metabolism, gastrointestinal function, body weight or appetite (e.g. domperidone, anticholinergic drugs (e.g. atropine), metoclopramide, erythromycin, hyoscine, orlistat, green tea extracts, Astragalus, St Johns Wort etc.) -substantial daily consumption of quinine, e.g. as part of quinine-based anti-malaria treatment (irregular consumption of small amounts of quinine, e.g. in tonic water, is acceptable) -regular medication that may affect any of the study outcomes (i.e. gastrointestinal motor or hormone function) and cannot be discontinued during the study -other food allergy -current gallbladder or pancreatic disease -coagulation abnormalities -oesophageal varices or strictures -cardiovascular or respiratory diseases that may affect any of the study outcomes and/or tolerance of the naso-duodenal tube -all types of epilepsy -individuals with low ferritin levels (females <15 ng/mL, males <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 that may affect any of the study outcomes and not explicitly listed above) -exposure to ionising radiation from X-ray machines or radioactive substances in the last 12 months for research purposes -high performance athletes, due to their specific dietary requirements and energy intakes (i.e. much higher than the average population), which affect gastrointestinal functions -current intake of > 2 standard alcoholic drinks on > 5 days per week, due to the known effects of alcohol on gastrointestinal function -current smokers/users of tobacco products (including pipe, chewing, cigarettes, cigars, sheesha, vaping) -recreational drug use (e.g. marijuana) -current intake of any illicit substance (since all of these, i.e. tobacco products, marijuana and illicit drugs may affect gastrointestinal functions) -vegetarians -inability to tolerate oro/naso-gastric tube -inability to comprehend study protocol -in premenopausal females, pregnancy, lactation or surgical sterilisation (a pregnancy test will be performed, using a urine sample, on the morning of study day); -female participants with irregular period cycles, since studies will be performed during the follicular phase, to avoid any influences of the different stages of the menstrual cycle on study outcomes.
Outcome results
None listed