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Trial registered on ANZCTR


Registration number
ACTRN12612001005842
Ethics application status
Approved
Date submitted
18/09/2012
Date registered
18/09/2012
Date last updated
18/09/2012
Type of registration
Prospectively registered

Titles & IDs
Public title
Does the drug Galvus enhance the effects of a protein preload to reduce blood glucose concentrations after a meal?
Scientific title
Does Galvus enhance the effects of a protein preload to reduce postprandial glycemia in patients with type 2 diabetes?
Secondary ID [1] 281253 0
CLAF237AAU04T
Universal Trial Number (UTN)
U1111-1134-8235
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes 287445 0
Condition category
Condition code
Metabolic and Endocrine 287782 287782 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
22 males with type 2 diabetes, treated with metformin monotherapy, will be studied, each on 4 separate occasions in a randomized, double-blind crossover fashion to evaluate the effects of:
(1) A protein preload (25 g chocolate-flavoured whey protein dissolved in 250 mL water (89 kcal)) in combination with placebo
(2) A protein preload (25 g chocolate-flavoured whey protein dissolved in 250 mL water (89 kcal)) in combination with vildagliptin (50 mg)
(3) A control preload (250 ml water with chocolate flavouring (8 kcal)) in combination with placebo
(4) A control preload (250 ml water with chocolate flavouring (8 kcal)) in combination with vildagliptin (50 mg)
on blood glucose, insulin, glucagon and total and intact GLP-1 and GIP concentrations, and the gastric emptying of a carbohydrate-containing meal. The study days will be separated by at least 7 days.

On the evening before each of the study days (~1900 h), participants will be given a standardised evening meal (McCain’s frozen beef lasagne (McCain Foods Proprietary Ltd); 2472 kJ) to consume with water. With this meal, participants will be instructed to take their usual metformin dose, as well as 50 mg of vildagliptin, or matched placebo. Following this meal, participants will be asked to fast from solids and liquids (other than water) until the following morning.

Participants will then attend the Discipline of Medicine at 0830 h on the following morning. On arrival, an intravenous cannula will be inserted into an antecubital vein for blood sampling. Following this (t = -90 min), a baseline blood sample will be taken, then participants will ingest either 50 mg of vildagliptin, or placebo, with 100 ml of water. One hour later (t = -30 min), they will consume a preload drink containing either 25 g chocolate-flavoured whey protein dissolved in 250 mL water (89 kcal), or control (250 ml water with chocolate flavouring (8 kcal)), within 2 minutes. Thirty minutes later (t = 0 min), participants will eat a meal consisting of 65 g powdered potato (Deb, Epping, NSW, Australia) and 20 g glucose, reconstituted with 200 mL water and 1 egg yolk containing 100 microlitres of 13C-octanoic acid. Participants will consume the meal within 5 minutes. Breath samples will be collected immediately before, and every 5 minutes after, meal ingestion in the first hour and every 15 minutes for a further 3 hours for the measurement of gastric emptying. Venous blood samples (~10 mL) will be taken immediately before the preload administration (t = -30 min), and at t = -15, 0, 15, 30, 60, 90, 120, 180 and 240 min for the measurements of blood glucose, insulin, GLP-1 and GIP (total and intact) and glucagon. At t = 240 minutes, the intravenous cannula will be removed, and participants will then be free to leave the laboratory. On each study day, a total of ~110 mL venous blood will be collected. At the same intervals used for blood sampling, appetite and gastrointestinal sensations will be assessed using 100 mm visual analogue scales.

Gastric emptying of the carbohydrate meal, labelled with 13C octanoic acid, will be measured by excretion of 13CO2 in the breath by mass spectrometer. This technique has been validated against the “gold-standard” scintigraphy. Half-emptying time (t50) and gastric emptying coefficient (GEC) will be calculated.
Intervention code [1] 285717 0
Treatment: Drugs
Comparator / control treatment
One tablet of Galvus (vildagliptin (50 mg)) will be taken on both the evening before, and the morning of the study.
Matched placebo tablets.
Control group
Placebo

Outcomes
Primary outcome [1] 288005 0
Blood glucose levels
Timepoint [1] 288005 0
Venous blood samples (~10 mL) will be taken immediately before the preload administration (t = -30 min), and at t = -15, 0, 15, 30, 60, 90, 120, 180 and 240 min for the measurements of blood glucose.
Secondary outcome [1] 299246 0
Insulin
Timepoint [1] 299246 0
Venous blood samples (~10 mL) will be taken immediately before the preload administration (t = -30 min), and at t = -15, 0, 15, 30, 60, 90, 120, 180 and 240 min for the measurements of plasma insulin concentrations.
Secondary outcome [2] 299247 0
Glucagon
Timepoint [2] 299247 0
Venous blood samples (~10 mL) will be taken immediately before the preload administration (t = -30 min), and at t = -15, 0, 15, 30, 60, 90, 120, 180 and 240 min for the measurements of plasma glucagon concentrations.
Secondary outcome [3] 299248 0
Glucagon-like peptide-1 (GLP-1) (total and active)
Timepoint [3] 299248 0
Venous blood samples (~10 mL) will be taken immediately before the preload administration (t = -30 min), and at t = -15, 0, 15, 30, 60, 90, 120, 180 and 240 min for the measurements of plasma GLP-1 (total and active) concentrations.
Secondary outcome [4] 299249 0
Glucose-dependent insulinotropic polypeptide (GIP) (total and active)
Timepoint [4] 299249 0
Venous blood samples (~10 mL) will be taken immediately before the preload administration (t = -30 min), and at t = -15, 0, 15, 30, 60, 90, 120, 180 and 240 min for the measurements of plasma GIP concentrations.
Secondary outcome [5] 299250 0
Gastric emptying rate
Timepoint [5] 299250 0
Breath samples will be collected immediately before, and every 5 minutes after, meal ingestion in the first hour and every 15 minutes for a further 3 hours for the measurement of gastric emptying.
Secondary outcome [6] 299251 0
Appetite perceptions and gastrointestinal symptoms
Timepoint [6] 299251 0
Visual analogue scale (VAS) questionnaires will be completed immediately before the preload administration (t = -30 min), and at t = -15, 0, 15, 30, 60, 90, 120, 180 and 240 min for the assessment of perceptions of appetite and gastrointestinal symptoms.

Eligibility
Key inclusion criteria
-Patients with type 2 diabetes (taking a stable dose of metformin, greater than or equal to 1500 mg/day for at least 3 months prior to the study)
-Body mass index of 25-35 kg/m2
Aged between 20-75 years, will be included in the study.
Minimum age
20 Years
Maximum age
75 Years
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
(1) significant gastrointestinal symptoms; disease or surgery
(2) inability to monitor blood glucose at home with a glucometer
(3) current use of any prescribed or non-prescribed medications, that may affect gastrointestinal function (except for metformin) within 48 hours of the study (e.g. domperidone and cisapride, anticholinergic drugs (e.g. atropine), metoclopramide, erythromycin, hyoscine, orlistat, green tea extracts, Astragalus, St John's Wort)
(4) current use of ACE inhibitors
(5) epilepsy
(6) cardiovascular (coronary heart disease, heart attack or failure, stroke) or respiratory disease (COPD, cystic fibrosis)
(7) any other significant illness as assessed by the investigator
(8) intake of > 20 g alcohol on a daily basis
(9) smokers (cigarettes, cigars, marijuana)
(10) donation of blood in the 12 weeks prior to enrolment in the study. Participants will also be instructed to abstain from donating blood for 12 weeks after study completion. A screening blood sample will be taken to ensure that only individuals with normal haemoglobin and iron levels are included in the study.
(11) consumption of a vegetarian diet
(12) inability to comprehend study protocol
(13) known lactose intolerance, intolerance or allergy to whey, allergy to vildagliptin
(14) liver function tests and creatinine clearance outside the following ranges
*Alanine aminotransferase (ALT) 0 -55 U/l
*Alkaline phosphatase 30 - 110 U/l
*Aspartate transaminase 0 - 45 U/l
*Bilirubin 6 - 24 mmol/l
Calculated creatinine clearance will be determined as follows:
Cr clearance = [140 - age (years) x weight (kg)] / serum creatinine (micromol/L)
with a creatinine clearance cut-off of <50 ml/min AND/OR serum creatinine concentration >0.12mmol/l will be excluded.

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)
Pharmacy will randomise the patients to receive each of the four treatments in a double-blind fashion (i.e. the participants and the investigators responsible for data analysis) will be blinded to the treatment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation by using a randomization table created by a computer software (i.e. computerised sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Not yet recruiting
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)

Funding & Sponsors
Funding source category [1] 286025 0
Commercial sector/Industry
Name [1] 286025 0
Novartis Pharmaceuticals Australia Pty. Ltd.
Address [1] 286025 0
54 Waterloo Road,
North Ryde, NSW, 2111
Country [1] 286025 0
Australia
Primary sponsor type
Individual
Name
Professor Michael Horowitz
Address
University of Adelaide Discipline of Medicine
Level 6, Eleanor Harrald Building
Royal Adelaide Hospital
North Terrace
Adelaide, SA, 5000
Country
Australia
Secondary sponsor category [1] 284840 0
Hospital
Name [1] 284840 0
Central Adelaide Local Health Network (ABN 96 269 526 412) (formerly Adelaide Health Service Inc) operating as Royal Adelaide Hospital
Address [1] 284840 0
North Terrace,
Adelaide, South Australia, 5000
Country [1] 284840 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288074 0
Royal Adelaide Hospital Research Ethics Committee
Ethics committee address [1] 288074 0
Royal Adelaide Hospital
North Terrace
Adelaide, SA, 5000
Ethics committee country [1] 288074 0
Australia
Date submitted for ethics approval [1] 288074 0
Approval date [1] 288074 0
04/07/2012
Ethics approval number [1] 288074 0
120624

Summary
Brief summary
To determine whether:
(i) A protein preload stimulates glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) secretion, and thereby reduces postprandial glycaemia following a carbohydrate-containing meal relative to a control condition.
(ii) Galvus (vildagliptin) enhances the effect of a protein preload to stimulate GLP-1 and GIP secretion, and thereby further reduces postprandial glycaemia following a carbohydrate-containing meal.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34727 0
Address 34727 0
Country 34727 0
Phone 34727 0
Fax 34727 0
Email 34727 0
Contact person for public queries
Name 17974 0
Dr Tanya Little
Address 17974 0
University of Adelaide Discipline of Medicine
Level 6, Eleanor Harrald Building
Royal Adelaide Hospital
North Terrace
Adelaide, SA, 5000
Country 17974 0
Australia
Phone 17974 0
+61882220724
Fax 17974 0
+61882233870
Email 17974 0
tanya.little@adelaide.edu.au
Contact person for scientific queries
Name 8902 0
Dr Tanya Little
Address 8902 0
University of Adelaide Discipline of Medicine
Level 6, Eleanor Harrald Building
Royal Adelaide Hospital
North Terrace
Adelaide, SA, 5000
Country 8902 0
Australia
Phone 8902 0
+61882220724
Fax 8902 0
+61882233870
Email 8902 0
tanya.little@adelaide.edu.au

No information has been provided regarding IPD availability
Summary results
No Results