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Trial registered on ANZCTR


Trial ID
ACTRN12613001158752
Ethics application status
Approved
Date submitted
11/10/2013
Date registered
18/10/2013
Date last updated
11/11/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
A study to evaluate whether the glucose-lowering efficacy of vildagliptin is influenced by the rate of intraduodenal glucose delivery in type 2 diabetes
Scientific title
A randomised, double-blind, placebo-controlled trial to determine the effect of the rate of intraduodenal glucose delivery on the glucose-lowering efficacy of vildagliptin in patients with type 2 diabetes
Secondary ID [1] 283390 0
Royal Adelaide Hospital Protocol Number: 130927
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes mellitus 290287 0
Condition category
Condition code
Metabolic and Endocrine 290678 290678 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 288114 0
Treatment: Drugs
Comparator / control treatment
Placebo tablet
Control group
Placebo

Outcomes
Primary outcome [1] 290698 0
Proportional reduction in the incremental areas under the curves (iAUCs) for blood glucose with vildagliptin vs. placebo, during intraduodenal glucose infusion at 4 vs. 2 kcal/min
Timepoint [1] 290698 0
T = -60 (ie. consumption of 50 mg vildagliptin or a matching placebo), 0 (ie. start of intraduodenal glucose infusion), 15, 30, 45, 60, 75, 90, and 120 min
Secondary outcome [1] 305058 0
Differences in the incremental areas under the curves (iAUCs) for plasma concentrations of intact GLP-1 and GIP, glucagon, insulin and C-peptide during intraduodenal glucose infusion at 4 vs. 2 kcal/min with vildagliptin vs. placebo
Timepoint [1] 305058 0
T = -60 (ie. consumption of 50 mg vildagliptin or a matching placebo), 0 (ie. start of intraduodenal glucose infusion), 15, 30, 45, 60, 75, 90, and 120 min
Secondary outcome [2] 305059 0
Differences in blood pressure (BP) and heart rate (HR) during intraduodenal glucose infusion at 4 vs. 2 kcal/min with vildagliptin vs. placebo.
Timepoint [2] 305059 0
BP and HR will be assessed using an automatic sphygmomanometer every 5 min after administration of 50 mg vildagliptin or a matching placebo until the end of intraduodenal glucose infusion.
Secondary outcome [3] 305084 0
Superior mesenteric artery (SMA) blood flow during intraduodenal glucose infusion at 4 vs. 2 kcal/min with vildagliptin vs. placebo.
Timepoint [3] 305084 0
SMA blood flow will be measured using doppler ultrasound every 15 min after administration of vildagliptin or placebo until the end of intraduodenal glucose infusion.

Eligibility
Key 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)
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

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)
numbered containers
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
computer-generated random number table
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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] 288113 0
Commercial sector/Industry
Name [1] 288113 0
Novartis Pharmaceuticals Australia Pty. Ltd.
Address [1] 288113 0
54 Waterloo Road
North Ryde, NSW, 2111

Country [1] 288113 0
Australia
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital
Address
North Terrace, Adelaide SA 5000
Country
Australia
Secondary sponsor category [1] 286834 0
None
Name [1] 286834 0
Address [1] 286834 0
Country [1] 286834 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290037 0
Royal Adelaide Hospital Human Research Ethics Committee
Ethics committee address [1] 290037 0
Level 3, Hanson Institute Royal Adelaide Hospital, North Terrace, Adelaide SA 5000
Ethics committee country [1] 290037 0
Australia
Date submitted for ethics approval [1] 290037 0
Approval date [1] 290037 0
24/09/2013
Ethics approval number [1] 290037 0

Summary
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.
Trial website
Trial related presentations / publications
None
Public notes

Contacts
Principal investigator
Name 43610 0
Prof Michael Horowitz
Address 43610 0
Discipline of Medicine, University of Adelaide
Level 6, Eleanor Harrald Building,
North Terrace
Royal Adelaide Hospital,
Adelaide SA 5000
Country 43610 0
Australia
Phone 43610 0
+61 8 82224327
Fax 43610 0
+61 8 82223870
Email 43610 0
michael.horowitz@adelaide.edu.au
Contact person for public queries
Name 43611 0
A/Prof Chris Rayner
Address 43611 0
Discipline of Medicine, University of Adelaide
Level 6, Eleanor Harrald Building,
North Terrace
Royal Adelaide Hospital,
Adelaide SA 5000
Country 43611 0
Australia
Phone 43611 0
+61 8 82222916
Fax 43611 0
+61 8 82223870
Email 43611 0
chris.rayner@adelaide.edu.au
Contact person for scientific queries
Name 43612 0
A/Prof Chris Rayner
Address 43612 0
Discipline of Medicine, University of Adelaide
Level 6, Eleanor Harrald Building,
North Terrace
Royal Adelaide Hospital,
Adelaide SA 5000
Country 43612 0
Australia
Phone 43612 0
+61 8 82222916
Fax 43612 0
+61 8 82223870
Email 43612 0
chris.rayner@adelaide.edu.au