None listed
Conditions
Brief summary
The purpose of this trial is to investigate the dose-related effects of intraduodenal administration of the bitter agonist, quinine, a non-nutritive (calorie-free) compound, on energy intake at a subsequent ad libitum buffet style meal, plasma gut hormone concentrations, and appetite perceptions in people with type 2 diabetes. We have found in one of our recent studies that quinine, given as a bolus in doses of 300 or 600 mg (in 10 ml water), potently slowed gastric emptying and lowered postprandial blood glucose. Moreover, we observed more potent blood glucose lowering effects when quinine was administered intraduodenally than intragastrically, suggesting that interaction of quinine with small intestinal receptors is required for potent effects. Therefore, based on these findings, this study aims to characterise the dose-related effects of intraduodenal quinine at these doses, on energy intake.
Interventions
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 ~4-4.5 hours 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 dinne
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 ~4-4.5 hours 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 13.5 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 given a standardised light breakfast (1 slice (30 g) whole meal bread, 10 g jam and a cup (200 ml) black tea; ~100 kcal), after which they 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. At 11.30 am, t = -31 min, a baseline blood sample (10 ml) will be taken, the participant will complete a VAS to assess appetite-related perceptions and GI symptoms as well as the Leeds Food Preference Questionnaire (LFPQ), which is a computerised behavioural task that provides measures of 'liking' and 'wanting' components of food preference and food reward. Immediately thereafter (t = -31 min), participants will receive either (i) 600 mg quinine, (ii) 300 mg quinine, or (iii) water into the duodenum. The adherence or fidelity to the intervention will be assessed or monitored by direct supervision of a research officer who will not be involved in data analysis. 10-ml blood samples for the measurement of plasma concentrations of hormones and glucose will be collected every 10 min (-20, -10, 0), and participants complete VAS questionnaires. At t = 0 min, participants will complete LFPQ and then be presented with a cold, buffet-style meal. Participants will be allowed 30 min to freely consume the meal until comfortably full. Immediately after the meal (t = 30 min) and then every 30 min (t = 60 and 90 min), blood samples will be collected and participants complete VAS questionnaires. At t = 90 min, the intravenous cannula will be removed and participants will be allowed 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
Male
Age
18 Years to 70 Years
Healthy volunteers
No
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. Blood glucose medications will be required to 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.
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 (females less than 15 ng/mL, males 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% or >7.9%; Any patient whose medication cannot be withheld for 48 hours for medical reasons; Estimated glomerular filtration rate <45 ml/min.
Outcome results
None listed