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Trial registered on ANZCTR


Trial ID
ACTRN12613001056785
Ethics application status
Approved
Date submitted
19/09/2013
Date registered
23/09/2013
Date last updated
26/02/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Vildagliptin in type 1 diabetes mellitus added to insulin
Scientific title
A randomised, double-blind, parallel arm, placebo controlled trial to determine the effect of vildagliptin used in combination with insulin therapy on glycaemic variability in adults with type 1 diabetes mellitus of at least 2 years duration.
Secondary ID [1] 283256 0
CLAF237U06T
Universal Trial Number (UTN)
Trial acronym
VITAL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
type 1 diabetes 290131 0
Glycamic variability 290132 0
Hypoglycaemia 290133 0
Condition category
Condition code
Metabolic and Endocrine 290518 290518 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Vildagliptin 50 mg twice daily ,orally will be added to usual insulin therapy for a period of 3 months with the comparator group receiving placebo. Adherence will be monitored by tablet return
Intervention code [1] 287989 0
Treatment: Drugs
Comparator / control treatment
This is a randomised double blind placebo controlled trial. Placebo will be a microcellulose tablet
Control group
Placebo

Outcomes
Primary outcome [1] 290542 0
Glycaemic variability. This will be assesed by continuous glucose monitoring and measurement of standard deviation of blood glucose levels over the period of one week
Timepoint [1] 290542 0
3 months
Secondary outcome [1] 304763 0
Post prandial blood glucose rise. This will be assessed by continuous glucose monitoring and mean glucose rise after meals
Timepoint [1] 304763 0
3 months
Secondary outcome [2] 304764 0
HbA1c. This will be measured by high-performance liquid chromatography (HPLC)
Timepoint [2] 304764 0
3 months
Secondary outcome [3] 304765 0
Insulin dose. This will be measured by patient diary
Timepoint [3] 304765 0
3 months
Secondary outcome [4] 304766 0
Body weight. This wil be measured at clinic visits using calibrated digital scales
Timepoint [4] 304766 0
3 months
Secondary outcome [5] 304767 0
CGMS glycaemic parameters. % time in normoglycaemia, hypoglycaemia and hyperglycaemia will be assesed from CGMS tracings
Timepoint [5] 304767 0
3 months
Secondary outcome [6] 304768 0
Effect of ultra sensitive c peptide as a measure of residual beta cell function on vildagliptin response. Ultra sensitive c peptide is available through Mercodia: Mercodia Ultrasensitive C-peptide ELISA
Timepoint [6] 304768 0
3 months
Secondary outcome [7] 304769 0
Effect of ultra sensitive c peptide on glycaemic variability. Correlation of c peptide with glycaemic variability will be assessed
Timepoint [7] 304769 0
Study initiation

Eligibility
Key inclusion criteria
Type 1 diabetes duration> 2 years
HbA1c 7.0% to 10.0%
MDI or CSII therapy
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Premix insulin regime
Type 2 diabetes
Severe hypoglycaemia in past 3 months
Pregnant, lactating or planning pregnancy

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)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation table generated by computer
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
Parallel
Other design features
Phase
Phase 3 / Phase 4
Type of endpoint(s)
Statistical methods / analysis
From CGM analyses obtained in people from this clinic who were on multiple insulin injections prior to commencing insulin pumps for treatment of type 1 diabetes, the change in SD was 0.2 mmol/L and the SD of the change in SD was 0.25. Average duration of diabetes was 16.1 years (range 4-28 years). For 80% power (2-sided calculation) with an alpha of 0.05 and assuming a difference between groups of 0.2, a minimum of 25 participants will be required in each arm of this trial (minimum total number 50 participants). To allow for screen failures and drop out rate between randomisation and 3 months (allow 20% extra), 60 participants will need to be screened.
In a previous study the percentage of patients who were C-peptide positive on the ultrasensitive C-peptide assay was 39.1% with duration of diabetes of 11-20 years.
Intention-to-treat analysis will be used for all randomised patients. The last observation will be carried forward in calculating the primary endpoint.

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)
VIC
Recruitment postcode(s) [1] 7373 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 288000 0
Commercial sector/Industry
Name [1] 288000 0
Novartis Pharmaceuticals Australia Pty Limited
Address [1] 288000 0
54 Waterloo Road,
North Ryde, NSW, 2111
Country [1] 288000 0
Australia
Primary sponsor type
Other
Name
BakerIDI Heart and Diabetes Institute
Address
75 Commercial Rd, Melbourne
VIC
3004
Country
Australia
Secondary sponsor category [1] 286722 0
None
Name [1] 286722 0
Address [1] 286722 0
Country [1] 286722 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289925 0
The Alfred Research and Ethics Unit
Ethics committee address [1] 289925 0
The Alfred Hospital, 55 Commercial Road, Melbourne, Victoria 3004, Australia
Ethics committee country [1] 289925 0
Australia
Date submitted for ethics approval [1] 289925 0
23/09/2013
Approval date [1] 289925 0
28/10/2013
Ethics approval number [1] 289925 0

Summary
Brief summary
Type 1 diabetes is associated with significant fluctuations in blood glucose levels in patients on multiple daily insulin injections or insulin pump therapy. This glycaemic variability limits patients ability to adequately control blood glucose due to its association with hypoglycaemia and subsequent high readings or 'rebounds'. The medication vildagliptin is currently used in the treatment of type 2 diabetes and in this setting has the ability to lower glucose and reduce hypoglycaemia. Its action is both on insulin producing cells, beta cells, and glucagon producing cells, alpha cells. Patients with type 1 diabetes have traditionally been thought to have no insulin production, however recent studies using a more sensitive assay have shown residual beta cell function in many type 1 patients after 10 years. This study is designed to assess the effects of vildagliptin in patients with type 1 diabetes and aspects of blood glucose control including glycaemic variablity. The hypothesis is that vildagliptin may reduce variability due to its action on both alpha and beta cell activity in a glucose dependent manner.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 43102 0
A/Prof Neale Cohen
Address 43102 0
BakerIDI Heart and Diabetes Institute
Level 4, 99 Commercial Rd
Melbourne
VIC 3004
Country 43102 0
Australia
Phone 43102 0
+61385321800
Fax 43102 0
Email 43102 0
neale.cohen@bakeridi.edu.au
Contact person for public queries
Name 43103 0
A/Prof Neale Cohen
Address 43103 0
BakerIDI Heart and Diabetes Institute
Level 4, 99 Commercial Rd
Melbourne
VIC 3004
Country 43103 0
Australia
Phone 43103 0
+61385321800
Fax 43103 0
Email 43103 0
neale.cohen@bakeridi.edu.au
Contact person for scientific queries
Name 43104 0
A/Prof Neale Cohen
Address 43104 0
BakerIDI Heart and Diabetes Institute
Level 4, 99 Commercial Rd
Melbourne
VIC 3004
Country 43104 0
Australia
Phone 43104 0
+61385321800
Fax 43104 0
Email 43104 0
neale.cohen@bakeridi.edu.au