Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614001117606
Ethics application status
Approved
Date submitted
3/10/2014
Date registered
22/10/2014
Date last updated
9/06/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
The role of glucagon-like peptide-1 (GLP-1) in glycaemic, triglyceride and energy expenditure responses to fat in type 2 diabetes.
Scientific title
Defining the role of endogenous glucagon-like peptide-1 (GLP-1) in the glycaemic, triglyceride and energy expenditure responses to fat in patients with Type 2 Diabetes (T2D) using Galvus (vildagliptin) and the GLP-1 receptor antagonist exendin (9-39)
Secondary ID [1] 285440 0
Nil.
Universal Trial Number (UTN)
U1111-1162-5983
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes 293200 0
Condition category
Condition code
Metabolic and Endocrine 293476 293476 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1: Galvus (vildagliptin) 50 mg (oral, single dose only) + intravenous infusion of 0.9% saline (for 210 minutes)
Arm 2: Placebo (oral, single dose only) + intravenous infusion of 0.9% saline (for 210 minutes)
Arm 3: Galvus (50 mg) (oral, single dose only) + exendin(9-39) (a glucagon-like peptide-1 (GLP-1) receptor antagonist, administered at a dose of 900 pmol/kg/min for 210 min)

Adherance will be monitored by the investigators who will administer the drugs in the laboratory. Plasma concentrations of GLP-1 will determine drug efficacy.

This is a cross-over study, each visit will be separated by at least 7 days.

On each day, participants will receive an intraduodenal infusion of fat (Intralipid, 2 kcal/min for 120 min, administered 60 min after ingestion of vildagliptin/placebo and commencement of i.v. infusion of exendin9-39/saline).
Intervention code [1] 290372 0
Treatment: Drugs
Comparator / control treatment
Placebo (matched microcellulose tablet)
Intravenous infusion of 0.9% saline
Control group
Placebo

Outcomes
Primary outcome [1] 293298 0
plasma triglyceride concentrations
Timepoint [1] 293298 0
t= 0, 15, 30, 45, 60, 90, 120, 150 and 180 minutes
Primary outcome [2] 293299 0
energy expenditure will be evaluated by indirect calorimetry
Timepoint [2] 293299 0
AUC 0-120 minutes
Primary outcome [3] 293349 0
respiratory quotient will be evaluated by indirect calorimetry
Timepoint [3] 293349 0
AUC 0-120 min
Secondary outcome [1] 310757 0
blood glucose will be assessed using a portable glucometer
Timepoint [1] 310757 0
t= 0, 15, 30, 45, 60, 90, 120, 150 and 180 minutes
Secondary outcome [2] 310758 0
plasma gut hormone concentrations (active glucagon-like peptide-1 (GLP-1) and glucose dependent insulinotropic peptide (GIP)) will be assessed using radioimmunoassays or ELISA
Timepoint [2] 310758 0
t= 0, 15, 30, 45, 60, 90, 120, 150 and 180 minutes
Secondary outcome [3] 310759 0
plasma catecholamine concentrations will be assayed
Timepoint [3] 310759 0
t= 0, 15, 30, 45, 60, 90, 120, 150 and 180 minutes
Secondary outcome [4] 310760 0
plasma insulin and glucagon concentrations will be determined using ELISAs
Timepoint [4] 310760 0
t= 0, 15, 30, 45, 60, 90, 120, 150 and 180 minutes
Secondary outcome [5] 310761 0
appetite perceptions (e.g. hunger, fullness, desire to eat) will be assessed using 100 mm visual analogue scale (VAS) questionnaires
Timepoint [5] 310761 0
t= 0, 15, 30, 45, 60, 90, 120, 150 and 180 minutes
Secondary outcome [6] 310762 0
gastrointestinal symptoms (e.g. bloating and nausea) will be assessed using 100 mm visual analogue scale (VAS) questionnaires
Timepoint [6] 310762 0
t= 0, 15, 30, 45, 60, 90, 120, 150 and 180 minutes
Secondary outcome [7] 310763 0
superior mesenteric artery blood flow will be assessed using ultrasound
Timepoint [7] 310763 0
AUC 0-120 min
Secondary outcome [8] 310764 0
blood pressure will be assessed using an automatic sphygmomanometer
Timepoint [8] 310764 0
AUC 0-120 minutes
Secondary outcome [9] 310830 0
heart rate will be assessed using an automatic sphygmomanometer
Timepoint [9] 310830 0
AUC 0-120 min

Eligibility
Key inclusion criteria
- Patients with type 2 diabetes managed by diet alone or Metformin
- glycated haemoglobin (HbA1c) greater than or equal to 6.0% and less than or equal to 7.9%
- body mass index of 25-35 kg/m2
- aged between 40-75 years
- Males and post-menopausal females (to control for the effect of the menstrual cycle on gut hormone secretion)
- 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
40 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- use of oral hypoglycaemic drugs other than Metformin or insulin
- significant gastrointestinal symptoms; disease or surgery
- current use of any prescribed or non-prescribed medications, that may affect gastrointestinal function 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)
- epilepsy
- coronary heart disease, heart attack or failure, stroke or respiratory disease (COPD, cystic fibrosis)
- any other significant illness as assessed by the investigator
- intake of > 20 g alcohol on a daily basis
- smokers (cigarettes, cigars, marijuana)
- donation of blood (either through Red Cross or research activities) 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.
- consumption of a vegetarian diet
- inability to comprehend study protocol
- known lactose intolerance, intolerance, allergy to vildagliptin
- 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 (micro mol/L)
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)
Participants will be randomised by the study pharmacist. Neither the investigators collecting the data, nor the participant, will be aware of study allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be performed using a randomisation table created by computer software (i.e. computerised sequence generation).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
Data will be analysed statistically using one-way or repeated measures ANOVAs, with treatment, time and treatment*time as factors. Post-hoc paired comparisons, corrected for multiple comparisons, will be performed if ANOVAs reveal significant effects. Statistical significance will be accepted at P<0.05.

Power calculations, performed by our biostatistician, determined that the inclusion of 16 participants would enable the detection of a 75 kcal/day difference in the effect of ID fat on resting energy expenditure between treatments (assuming SD of differences is equal to or less than 76). Significance was set at P = 0.008 to enable correction for multiple post-hoc testing and power of 80%. 20 participants will be included to give a power of 90%.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
3/11/2014
Actual
1/04/2016
Date of last participant enrolment
Anticipated
31/07/2018
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 3036 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 8799 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 290046 0
Commercial sector/Industry
Name [1] 290046 0
Novartis Pharmaceuticals Australia Pty. Ltd.
Country [1] 290046 0
Australia
Primary sponsor type
Individual
Name
Dr Tanya Little
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] 288735 0
None
Name [1] 288735 0
Address [1] 288735 0
Country [1] 288735 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291755 0
Royal Adelaide Hospital Research Ethics Committee
Ethics committee address [1] 291755 0
Ethics committee country [1] 291755 0
Australia
Date submitted for ethics approval [1] 291755 0
Approval date [1] 291755 0
02/10/2014
Ethics approval number [1] 291755 0
HREC/14/RAH/334

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 51886 0
Dr Tanya Little
Address 51886 0
University of Adelaide Discipline of Medicine
Level 6, Eleanor Harrald Building
Royal Adelaide Hospital
North Terrace, Adelaide, SA, 5000
Country 51886 0
Australia
Phone 51886 0
+61883132999
Fax 51886 0
Email 51886 0
[email protected]
Contact person for public queries
Name 51887 0
Tanya Little
Address 51887 0
University of Adelaide Discipline of Medicine
Level 6, Eleanor Harrald Building
Royal Adelaide Hospital
North Terrace, Adelaide, SA, 5000
Country 51887 0
Australia
Phone 51887 0
+61883132999
Fax 51887 0
Email 51887 0
[email protected]
Contact person for scientific queries
Name 51888 0
Tanya Little
Address 51888 0
University of Adelaide Discipline of Medicine
Level 6, Eleanor Harrald Building
Royal Adelaide Hospital
North Terrace, Adelaide, SA, 5000
Country 51888 0
Australia
Phone 51888 0
+61883132999
Fax 51888 0
Email 51888 0
[email protected]

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
SourceTitleYear of PublicationDOI
EmbaseRole of endogenous glucagon-like peptide-1 enhanced by vildagliptin in the glycaemic and energy expenditure responses to intraduodenal fat infusion in type 2 diabetes.2020https://dx.doi.org/10.1111/dom.13906
N.B. These documents automatically identified may not have been verified by the study sponsor.