None listed
Conditions
Brief summary
Emerging evidence of preclinical studies suggests that bitter substances in the gut can reduce appetite and slow the emptying of meals from the stomach, by stimulating GI hormone release. The purpose of this study is to determine the importance of the region of small intestine exposed, and the role of bitter taste signalling, to the release of GI hormones and energy intake responses in both health and T2DM. we wish to investigate whether the non-nutritive bitter taste flavouring, denatonium benzoate (DB), and the low-nutritive bitter taste amino acid, leucine, induce substantially more glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) secretion when infused into the ileum than the duodenum, associated with greater suppression on energy intake in both healthy subjects and patients with T2DM.
Interventions
Following enrolment, each subject will be studied on 5 occasions, separated by at least 7 days, in a double-blind, randomized fashion.
On each study day, a customised multi-lumen silicone catheter will be inserted through an anesthetized nostril and allowed to pass into the small intestine by peristalsis. The catheter will be positioned with the two infusion ports (i.e. proximal and distal small intestinal infusion ports) located at 13 cm (i.e. the duodenum) and 190 cm (i.e. the ileum) beyond th
Following enrolment, each subject will be studied on 5 occasions, separated by at least 7 days, in a double-blind, randomized fashion. On each study day, a customised multi-lumen silicone catheter will be inserted through an anesthetized nostril and allowed to pass into the small intestine by peristalsis. The catheter will be positioned with the two infusion ports (i.e. proximal and distal small intestinal infusion ports) located at 13 cm (i.e. the duodenum) and 190 cm (i.e. the ileum) beyond the pylorus, respectively, while subjects laid in a supine position. An intravenous cannula will be placed into a vein on the dorsum of the hand, which will be kept warm with a heat pad to allow sampling of “arterialised” blood. Once the intraluminal catheter is correctly positioned, one of the following 5 treatments will be administered: (i) duodenal (150 mL 0.9% saline)+ ileal saline (150 mL 0.9% saline) (i.e. control) (ii) duodenal DB (30mg dissolved in 0.9% saline to 150 mL)+ ileal saline (150 mL 0.9% saline) (i.e. duodenal DB) (iii) duodenal saline (150 mL 0.9% saline) + ileal DB (30 mg, dissolved in 0.9% saline to 150 mL) (i.e. ileal DB) (iv) duodenal leucine (5 g dissolved in 0.9% saline to 150 mL) + ileal saline (150 mL 0.9% saline) (i.e. duodenal leucine), and (v) duodenal saline (150 mL 0.9% saline) + ileal leucine (5 g dissolved in 0.9% saline to 150 mL). Each treatment will be administered during t = 0-60 min by one of the medically trained investigators. At t = 60 min, the catheter will be removed.
Sponsors
University of Adelaide
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
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
- Healthy males and females aged from 18 to 70 years - Body mass index (BMI) from 18 to 30 kg/m2 - HbA1c less than 5.7% - Fasting blood glucose less than 5.6 mmol/L Additional inclusion criteria include: haemoglobin above the lower limit of the normal range (ie. more than 135g/L for men and 115g/L for women), and ferritin above the lower limit of normal (ie. more than 30ng/mL for men and more than 20mg/mL for women)
Exclusion criteria
Use of any medication that may influence gastrointestinal motor function, body weight or appetite (e.g. antihypertensive drugs, domperidone and cisapride, anticholinergic drugs (e.g. atropine), metoclopramide, erythromycin, hyoscine, orlistat, green tea extracts, Astragalus, St. John's Wort etc.) Evidence of drug abuse, consumption of more than 20 g alcohol or 10 cigarettes on a daily basis History of gastrointestinal disease, including significant upper or lower gastrointestinal symptoms, pancreatitis, or previous gastrointestinal surgery (other than uncomplicated appendicectomy or cholecystectomy) Other significant illness, including epilepsy, cardiovascular or respiratory disease Impaired renal or liver function (as assessed by calculated creatinine clearance < 90 mL/min or abnormal liver function tests (> 2 times upper limit of normal range)) Donation of blood within the previous 3 months Participation in any other research studies within the previous 3 months Inability to give informed consent Female participants who are pregnant or planning for pregnancy, or are lactating Vegetarians
Outcome results
None listed