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Trial registered on ANZCTR

Registration number

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]

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

Condition category

Condition code

Metabolic and Endocrine

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]

Treatment: Drugs

Comparator / control treatment

Placebo tablet

Control group

Placebo

Outcomes

Primary outcome [1]

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]

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]

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]

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]

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]

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]

Superior mesenteric artery (SMA) blood flow during intraduodenal glucose infusion at 4 vs. 2 kcal/min with vildagliptin vs. placebo.

Timepoint [3]

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

Sex

Both males and females

Can healthy volunteers participate?

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

1/11/2013

Actual

16/01/2014

Date of last participant enrolment

Anticipated

Actual

2/06/2015

Date of last data collection

Anticipated

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Novartis Pharmaceuticals Australia Pty. Ltd.

Address [1]

54 Waterloo Road
North Ryde, NSW, 2111

Country [1]

Australia

Primary sponsor type

Hospital

Name

Royal Adelaide Hospital

Address

North Terrace, Adelaide SA 5000

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Royal Adelaide Hospital Human Research Ethics Committee

Ethics committee address [1]

Level 3, Hanson Institute Royal Adelaide Hospital, North Terrace, Adelaide SA 5000

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

24/09/2013

Ethics approval number [1]

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

Prof Michael Horowitz

Address

Discipline of Medicine, University of Adelaide
Level 6, Eleanor Harrald Building,
North Terrace
Royal Adelaide Hospital,
Adelaide SA 5000

Country

Australia

Phone

+61 8 82224327

Fax

+61 8 82223870

michael.horowitz@adelaide.edu.au

Contact person for public queries

Name

Chris Rayner

Address

Discipline of Medicine, University of Adelaide
Level 6, Eleanor Harrald Building,
North Terrace
Royal Adelaide Hospital,
Adelaide SA 5000

Country

Australia

Phone

+61 8 82222916

Fax

+61 8 82223870

chris.rayner@adelaide.edu.au

Contact person for scientific queries

Name

Chris Rayner

Address

Discipline of Medicine, University of Adelaide
Level 6, Eleanor Harrald Building,
North Terrace
Royal Adelaide Hospital,
Adelaide SA 5000

Country

Australia

Phone

+61 8 82222916

Fax

+61 8 82223870

chris.rayner@adelaide.edu.au

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Small intestinal glucose delivery affects the lowering of blood glucose by acute vildagliptin in type 2 diabetes.	2016	https://dx.doi.org/10.1210/jc.2016-2813

N.B. These documents automatically identified may not have been verified by the study sponsor.

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Documents added manually

Documents added automatically