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Trial registered on ANZCTR


Registration number
ACTRN12617000016336
Ethics application status
Approved
Date submitted
21/12/2016
Date registered
5/01/2017
Date last updated
24/02/2020
Date data sharing statement initially provided
15/01/2019
Date results information initially provided
15/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Does empagliflozin preserve pancreas function in recently-diagnosed type 1 diabetes?
Scientific title
Feasibility and safety of SGLT2 inhibition by empagliflozin for the preservation of pancreas function in recent-onset type 1 diabetes.
Secondary ID [1] 290796 0
SGLT-T1D
Universal Trial Number (UTN)
Trial acronym
n/a
Linked study record
n/a

Health condition
Health condition(s) or problem(s) studied:
type 1 diabetes 301440 0
Condition category
Condition code
Metabolic and Endocrine 301160 301160 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Empagliflozin 25mg orally daily for 6 months. Compliance will be monitored by assessing drug packets returned.
Intervention code [1] 296708 0
Treatment: Drugs
Comparator / control treatment
No comparator - safety and feasibility study
Control group
Uncontrolled

Outcomes
Primary outcome [1] 300573 0
Protocol compliance, measured by the frequency of deviation from the study protocol. Deviations will be assessed by pill counts at monthly visits and by reviewing visit data, collected monthly for the first 3 months and then 6-weekly up to 9 months after starting study drug.
Timepoint [1] 300573 0
9 months after starting study drug.
Secondary outcome [1] 330340 0
Number and severity of adverse events.
Adverse events will be reported directly to the medical monitor by email or telephone. The severity will be graded 1, 2, 3, 4 and 5 respectively for mild, moderate, severe and undesirable, life-threatening and disabling, and fatal events. Attribution will be assigned as follows:
1. Unrelated: The adverse event is clearly not related to empagliflozin.
2. Unlikely: The adverse event is doubtfully related to empagliflozin.
3. Possible: The adverse event may be related to empagliflozin.
4. Probable: The adverse event is likely related to empagliflozin.
5. Definite: The adverse event is clearly related to empagliflozin.
Timepoint [1] 330340 0
9 months after starting study drug.
Secondary outcome [2] 330341 0
Participant quality of life and diabetes distress, assessed using SF-36 and DDS-17 questionnaires (composite outcome).
Timepoint [2] 330341 0
3, 6 and 9 months after starting study drug.
Secondary outcome [3] 330342 0
Beta cell function, defined as the C-peptide area under the curve (AUC) for two hours following a liquid meal. Serum C-peptide will be measured by Royal Melbourne Hospital Biochemistry Laboratory.
Timepoint [3] 330342 0
The C-peptide AUC will be calculated from results obtained at -10, -5, 15, 30, 60, 90 and 120 minutes after the mixed meal. The C-peptide AUC will be calculated at 3, 6 and 9 months after starting study drug.
Secondary outcome [4] 330343 0
Glycaemic variability, measured using a masked iPro subcutaneous continuous glucose monitor, worn for 96 hours.
Timepoint [4] 330343 0
3, 6 and 9 months after starting study drug.
Secondary outcome [5] 330344 0
HbA1c measured by Melbourne Health Pathology
Timepoint [5] 330344 0
3, 6 and 9 months after starting study drug.
Secondary outcome [6] 330345 0
Systolic and diastolic blood pressure, measured using an automated sphygmomanometer.
Timepoint [6] 330345 0
3, 6 and 9 months after starting study drug.
Secondary outcome [7] 330346 0
Body weight and body composition, measured using Tanita BC-601 impedance scales (composite outcome).
Timepoint [7] 330346 0
3, 6 and 9 months after starting study drug.

Eligibility
Key inclusion criteria
Age between 18 and 40 years at time of consent
Type 1 diabetes diagnosed within 100 days of the month 0 visit with antibodies against at least one of the GAD, IA2, ZnT8 or insulin antigens, measured by an accredited clinical laboratory
Demonstrated ability to comply with insulin prescription and to record home glucose readings at least four times a day
A meal-stimulated C-peptide >0.07nmol/l (>0.2ng/ml)
Minimum age
18 Years
Maximum age
40 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Contra-indication to empagliflozin
Serious co-morbidity deemed by the study clinician to pose unacceptable risk
Unwilling to accept the rigors of the study, including four meal tolerance tests and frequent sustained periods of home glucose and ketone monitoring
If female: pregnancy, breast feeding or a desire for pregnancy during the study
If female with reproductive potential, refusal to use contraception during the study

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
n/a
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
n/a
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
nil
Phase
Phase 2
Type of endpoint(s)
Safety
Statistical methods / analysis
Missing data, where appropriate, will be filled by multiple imputation. Descriptive statistics will be used to describe baseline characteristics of study cohort and report protocol compliance and adverse events. Changes in beta-cell function over time will be analysed using Friedman test while Wilcoxon sign-rank test will be used to assess overall change. P<0.05 will be considered significant.

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 hospital [1] 7171 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment postcode(s) [1] 14932 0
3050 - Parkville

Funding & Sponsors
Funding source category [1] 295218 0
Hospital
Name [1] 295218 0
Royal Melbourne Hospital
Address [1] 295218 0
Grattan St
Parkville, VIC, 3050
Country [1] 295218 0
Australia
Primary sponsor type
Hospital
Name
Melbourne Health
Address
Research Directorate
Royal Melbourne Hospital
Grattan St
Parkville, VIC, 3050
Country
Australia
Secondary sponsor category [1] 294046 0
None
Name [1] 294046 0
Address [1] 294046 0
Country [1] 294046 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296563 0
Melbourne Health HREC
Ethics committee address [1] 296563 0
Royal Melbourne Hospital
Grattan St
Parkville, VIC, 3050
Ethics committee country [1] 296563 0
Australia
Date submitted for ethics approval [1] 296563 0
01/12/2016
Approval date [1] 296563 0
20/12/2016
Ethics approval number [1] 296563 0
2016.367

Summary
Brief summary
Empagliflozin is used to treat type 2 diabetes. It works by promoting loss of glucose in the urine. Recent evidence suggests this drug might help preserve pancreas function in people with diabetes. This study will assess the feasibility and safety of this approach in people who are within 100 days of being diagnosed with type 1 diabetes.
Trial website
n/a
Trial related presentations / publications
n/a
Public notes
n/a

Contacts
Principal investigator
Name 71306 0
A/Prof John Wentworth
Address 71306 0
Diabetes and Endocrinology
Royal Melbourne Hospital
Grattan St
Parkville, VIC, 3050
Country 71306 0
Australia
Phone 71306 0
+61 3 93427000
Fax 71306 0
+61 3 93470852
Email 71306 0
wentworth@wehi.edu.au
Contact person for public queries
Name 71307 0
A/Prof John Wentworth
Address 71307 0
Diabetes and Endocrinology
Royal Melbourne Hospital
Grattan St
Parkville, VIC, 3050
Country 71307 0
Australia
Phone 71307 0
+61 3 93427000
Fax 71307 0
+61 3 93470852
Email 71307 0
wentworth@wehi.edu.au
Contact person for scientific queries
Name 71308 0
A/Prof John Wentworth
Address 71308 0
Diabetes and Endocrinology
Royal Melbourne Hospital
Grattan St
Parkville, VIC, 3050
Country 71308 0
Australia
Phone 71308 0
+61 3 93427000
Fax 71308 0
+61 3 93470852
Email 71308 0
wentworth@wehi.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All clinical and biochemical data from the trial
When will data be available (start and end dates)?
31/12/2019 indefinitely
Available to whom?
Any researcher, on application to A/Prof John Wentworth
Available for what types of analyses?
Any
How or where can data be obtained?
Email of de-identified excel spreadsheet
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
Yes
Journal publication details
Publication date and citation/details [1] 7047 0
John M. Wentworth, Spiros Fourlanos, Peter G. Colman, Leonard C. Harrison,
A pilot study of the feasibility of empagliflozin in recent-onset type 1 diabetes,
Metabolism Open,
Volume 5,
2020,
100021,
ISSN 2589-9368,
https://doi.org/10.1016/j.metop.2020.100021.
Attachments [1] 7047 0
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary
This study demonstrated that it was feasible and appeared safe to treat adults with recent-onset type 1 diabetes with a tablet called empagliflozin. Treatment was associated with decreased insulin requirements and preservation of beta cell function. However, a larger placebo-controlled study will be needed to show that these effects were due to the tablet rather than the natural history of early type 1 diabetes.