None listed
Conditions
Brief summary
After meals, the small intestine is stimulated to release a number of hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). These two hormones play an important role in regulating blood sugar concentrations (by stimulating insulin secretion). The effects of these hormones in the body can be prolonged by a drug called vildagliptin, which is known to improve blood sugar control in people with type 2 diabetes. Because secretion of the hormones GLP-1 and GIP is influenced by how rapidly glucose enters the small intestine, we want to investigate whether the ability of vildagliptin to reduce blood sugar levels is also affected by the rate of glucose entry to the small intestine. Because the preservation of GLP-1 and GIP by vildagliptin may affect heart rate, blood pressure and abdominal blood flow in response to glucose infusion into the small intestine, we also want to measure heart rate, blood pressure and abdominal blood flow (using ultrasound scanning) during the study.
Interventions
Each subject will undergo 4 study visits, separated by at least one week, in double-blind, randomised fashion. On each day, an intraduodenal catheter (diameter 3.5 mm; Dentsleeve International) will be inserted through an anaesthetised nostril and allowed to pass through the stomach and into the duodenum by peristalsis. The catheter will be positioned with the intraduodenal infusion port located 14.5 cm distal to the pylorus. The correct positioning of the catheter will be maintained by continuo
Each subject will undergo 4 study visits, separated by at least one week, in double-blind, randomised fashion. On each day, an intraduodenal catheter (diameter 3.5 mm; Dentsleeve International) will be inserted through an anaesthetised nostril and allowed to pass through the stomach and into the duodenum by peristalsis. The catheter will be positioned with the intraduodenal infusion port located 14.5 cm distal to the pylorus. The correct positioning of the catheter will be maintained by continuous measurement of the transmucosal potential difference (TMPD) between the most distal antral channel (~ -40 mV) and the most proximal duodenal channel (~ 0 mV). 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 catheter is correctly positioned, a 50 mg tablet of vildagliptin, or matching placebo, will be administered orally with 30 mL water (t = -60 min). 60 min later (t = 0 min), each subject will receive an intraduodenal infusion of glucose, consisting of 60 g glucose with 10.08 g sodium chloride, or 120 g glucose dissolved in water to a volume of 480 mL, over 120 min (1390 mOsmol/L and 4 mL/min, 2 or 4 kcal/min). Thus, the 4 study treatments are: (1). 50 mg vildagliptin + intraduodenal infusion of 60 g glucose with 10.08 g sodium chloride; (2). 50 mg vildagliptin + intraduodenal infusion of 120 g glucose dissolved in water to a volume of 480 mL; (3). Placebo + intraduodenal infusion of 60 g glucose with 10.08 g sodium chloride; (4). Placebo + intraduodenal infusion of 120 g glucose dissolved in water to a volume of 480 mL.
Sponsors
Royal Adelaide Hospital
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used)
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Type 2 diabetes (World Health Organisation (WHO) criteria), managed by diet alone (i.e. no oral hypoglycaemic drugs or insulin); Body mass index (BMI) 20 - 40 kg/m2; Males and post-menopausal females (to control for the effect of the menstrual cycle on gut hormone secretion); Glycated haemoglobin (HbA1c) greater than or equal to 6.0% and less than or equal to 7.9%; Haemoglobin above the lower limit of the normal range (i.e. >135g/L for men and 115g/L for women), and ferritin above the lower limit of normal (i.e. >10mcg/L)
Exclusion criteria
Use of any medication that may influence BP, 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; Autonomic nerve damage (as assessed by standardised cardiovascular reflex tests); 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)); Allergy to vildagliptin or any other ‘gliptin’; Donation of blood within the previous 3 months; Participation in any other research studies within the previous 3 months; Females who are pre-menopausal; Inability to give informed consent; Vegetarians
Outcome results
None listed