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Trial registered on ANZCTR


Registration number
ACTRN12617001168347
Ethics application status
Approved
Date submitted
25/07/2017
Date registered
9/08/2017
Date last updated
9/08/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Metformin in Pre-diabetes Patients and Stroke study
Scientific title
Evaluating the safety and tolerability of Metformin XR in patients with pre-diabetes admitted with a stroke.
Secondary ID [1] 292525 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pre-diabetes 304173 0
Stroke 304174 0
Condition category
Condition code
Stroke 303499 303499 0 0
Ischaemic
Stroke 303500 303500 0 0
Haemorrhagic
Metabolic and Endocrine 303501 303501 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Metformin XR starting at 500mg daily and increase to a total daily dose of 1500mg daily after 1 month from intervention (If the dose of Metformin XR 500mg daily was tolerated at the one month follow up phone call, the dose will be tripled from 500mg daily to 1500mg daily. )
Intervention will commence within 6 week from stroke
The administartion is oral tablet
The duration of administartion will be 4 months
Compliance will check by counting the remaining tablets at 1 month and over 2.5 months from intervention over follow up phone calls
Intervention code [1] 298710 0
Treatment: Drugs
Comparator / control treatment
Receiving usual care. Usual care for pre-diabetes includes advice on dietary and lifestyle improvements, advice of regular physical exercise and weight loss as well as advice on smoking cessation or avoidance.
Control group
Active

Outcomes
Primary outcome [1] 302874 0
Safety and tolerability of Metformin XR assessed by using a validated side effects questionnaire
(Pereira DI, Couto Irving SS, Lomer MC, Powell JJ. A rapid, simple questionnaire to assess gastrointestinal symptoms after oral ferrous sulphate supplementation. BMC Gastroenterol. 2014 Jun 4;14:103. )
Timepoint [1] 302874 0
4 month post commencement of intervention
Secondary outcome [1] 337284 0
HbA1c levels measured in fasted blood samples using immunoassay method
Timepoint [1] 337284 0
4 month post commencement of intervention
Secondary outcome [2] 337362 0
fasting glucose levels measured using Hexokinase
Timepoint [2] 337362 0
4 month post commencement of intervention
Secondary outcome [3] 337363 0
C-peptide using ECLIA method
Timepoint [3] 337363 0
4 month post commencement of intervention
Secondary outcome [4] 337364 0
fasting lipid profile using enzymatic colorimetric method
Timepoint [4] 337364 0
4 month post commencement of intervention
Secondary outcome [5] 337365 0
blood pressure using digital blood pressure monitoring
Timepoint [5] 337365 0
4 month post commencement of intervention
Secondary outcome [6] 337366 0
urine albumin to creatinine ratio. Urea measured using Urease/GLDH and Creatinin by using Jaffe reaction method
Timepoint [6] 337366 0
4 month post commencement of intervention
Secondary outcome [7] 337367 0
body mass index calculated as weight /( height)2
Timepoint [7] 337367 0
4 month post commencement of intervention
Secondary outcome [8] 337368 0
waist circumference measured as the abdominal circumference just above the iliac crest in a standing and relaxed position
Timepoint [8] 337368 0
4 month post commencement of intervention

Eligibility
Key inclusion criteria
Age more than 18 years
Had an ischaemic stroke or TIA who are stable at least with a 6 week period following stroke
Modified Rankin Scale less than or equal to 3
HbA1c levels 5.7 to 6.4%
Minimum age
18 Years
Maximum age
90 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Age >90 years
Pre-existing diabetes
Estimated glomerular filtration rate (eGFR) < 60ml/min/1.73m2
Hepatic insufficiency (liver function tests >2x upper limit of normal)
Active drug or heavy alcohol use
Metastatic cancer
Pregnancy or breastfeeding
Weight less than 50kg
Use of hypoglycaemic agents, opioids, corticosteroids
Patients unlikely to survive for more than 6 months
Patients unavailable for repeated follow up and unlikely of participate in trial requirements, participation in other interventional trials

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Safety/efficacy
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)
VIC
Recruitment hospital [1] 8612 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 16720 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 297093 0
Charities/Societies/Foundations
Name [1] 297093 0
Stroke Foundation
Address [1] 297093 0
Level 7, 461 Bourke Street, Melbourne VIC 3000
Country [1] 297093 0
Australia
Primary sponsor type
Hospital
Name
Austin Health, Dr Elif Ekinci
Address
145 Studley Rd, Heidelberg VIC 3084
Country
Australia
Secondary sponsor category [1] 296101 0
None
Name [1] 296101 0
Address [1] 296101 0
Country [1] 296101 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298271 0
Austin Health
Ethics committee address [1] 298271 0
Austin Hospital
145 Studley Road
PO Box 5555
Heidelberg
Victoria
Australia 3084
Ethics committee country [1] 298271 0
Australia
Date submitted for ethics approval [1] 298271 0
11/01/2017
Approval date [1] 298271 0
20/03/2017
Ethics approval number [1] 298271 0
HREC/17/Austin/47

Summary
Brief summary
This is an off-label, randomized, open blinded end-point study to determine the safety and tolerability of Metformin XR administration starting at 500mg daily to a maximum total daily dose of 1500mg XR daily on discharge in patients with pre-diabetes (defined as an HbA1c of 5.7-6.4%) admitted with a stroke.
During an acute stroke admission or following a recent stroke admission, patients who are recruited into the trial will be randomized (in a 1:1 ratio) to either the active arm, receiving Metformin or usual care for a total of 4 months. Usual care for pre-diabetes includes advice on dietary and lifestyle improvements, advice of regular physical exercise and weight loss as well as advice on smoking cessation or avoidance.
At baseline, we will record clinical and biochemical characteristics, cardiovascular risk factors and medication use. One month into the study, a phone call follow up will occur and participants in both groups will be asked to complete a side effect questionnaire and compliance determined. A second follow up phone call will occur at 2.5 months and participants will again be asked to complete the questionnaire and asked about compliance.
Finally a physical study visit will be scheduled at four months following randomization. At this last visit, patients will complete the same questionnaire to determine their compliance and nature of any of the side-effects of the treatment. At both physical study visits, the fasting glucose levels, HbA1c, C-peptide, fasting lipid profile, blood pressure, urine albumin to creatinine ratio, body mass index (BMI), waist circumference, blood pressure, and lipid profile will be assessed.
Questions regarding side effects and completion of the side effect questionnaire during both follow up phone calls and second physical visit will be performed with a blinded investigator.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 76546 0
Dr Elif Ekinci
Address 76546 0
Level: 02 Room: 106, Boronia Building, Austin Repatriation Hospital
300 Waterdale Rd, Ivanhoe, VIC, 3079
Country 76546 0
Australia
Phone 76546 0
+61 (03) 9496 2250
Fax 76546 0
Email 76546 0
elif.ekinci@austin.org.au
Contact person for public queries
Name 76547 0
Mrs Marjan Tabesh
Address 76547 0
Level: 02 Room: 112, Boronia Building, Austin Repatriation Hospital,
300 Waterdale Rd, Ivanhoe, VIC, 3079
Country 76547 0
Australia
Phone 76547 0
+61 (03) 9496 2124
Fax 76547 0
Email 76547 0
mtabesh@student.unimelb.edu.au
Contact person for scientific queries
Name 76548 0
Mrs Marjan Tabesh
Address 76548 0
Level: 02 Room: 112, Boronia Building, Austin Repatriation Hospital
300 Waterdale Rd, Ivanhoe, VIC, 3079
Country 76548 0
Australia
Phone 76548 0
+61 (03) 9496 2124
Fax 76548 0
Email 76548 0
mtabesh@student.unimelb.edu.au

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