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Trial registered on ANZCTR


Trial ID
ACTRN12612000660886
Ethics application status
Approved
Date submitted
18/06/2012
Date registered
20/06/2012
Date last updated
29/08/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Metformin in overweight adults with type 1 diabetes mellitus
Scientific title
The effect of metformin on glucose control, weight, insulin dose and blood lipids in overweight adults with type 1 diabetes.
Secondary ID [1] 280165 0
Nil
Universal Trial Number (UTN)
1111-1129-1148
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 diabetes mellitus 286090 0
Overweight/obesity 286091 0
Condition category
Condition code
Metabolic and Endocrine 286284 286284 0 0
Diabetes
Diet and Nutrition 286285 286285 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Metformin dose will start at one tablet a day (500 mg extended release) and be increased to a maximum of 2,000 mg at the end of one month. The dose will be increased as tolerated by the patient. If after one week one tablet at night has been tolerated (i.e. no diarrhoea or indigestion) then the dose will be increased to two tablets at night. After a further week if the study medication is not causing any problems, a morning dose will be introduced. The next week another tablet in the morning will be added, so that at the end of the month the patients will be taking two tablets twice per day. Duration of treatment is one year.
Intervention code [1] 284491 0
Treatment: Drugs
Comparator / control treatment
Placebo is identical in taste and appearance but without the active ingredient
Control group
Placebo

Outcomes
Primary outcome [1] 286754 0
Glucose control measured as glycated hemoglobin (HbA1c) level in blood sample.
Timepoint [1] 286754 0
0, 3, 6, 9, 12 months
Primary outcome [2] 286755 0
Body mass index (BMI), calculated based on measured weight and height.
Timepoint [2] 286755 0
0, 1, 3, 6, 9, 12 months
Primary outcome [3] 286756 0
Insulin dose requirements, patients will be instructed to record daily insulin dose (units) in a diary.
Timepoint [3] 286756 0
0, 1, 3, 6, 9, 12 months
Secondary outcome [1] 296595 0
Fasting blood lipids measured in a blood sample.
Timepoint [1] 296595 0
0, 3, 6, 9, 12 months
Secondary outcome [2] 296600 0
Number of hypoglycemic events and adverse events such as feeling sick, vomiting, diarrhoea, stomach pain, loss of appetite and taste disturbances recorded by patients in a diary.
Timepoint [2] 296600 0
0, 1, 3, 6, 9,12 months
Secondary outcome [3] 296601 0
Waist/hip ratio calculated based on measured waist and hip circumference.
Timepoint [3] 296601 0
0,1, 3, 6, 9, 12 months
Secondary outcome [4] 297977 0
High sensitivity C-reactive protein (hsCRP) measured in a blood sample
Timepoint [4] 297977 0
0, 3, 6, 9, 12 months

Eligibility
Key inclusion criteria
Type 1 diabetes mellitus for at least 2 years diagnosed before the age of 25 years, BMI>=27 kg/m2, HbA1c>= 7.5%, age 18-65 years, CrCl >= 45 ml/min
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Contraindications to metformin (such as hepatic failure, renal failure, lactation), hypoglycemic unawareness, pregnancy, history of drug or alcohol abuse, alcoholism, inability to comply, serious co-morbidities.

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)
The subjects will be recruited from the Diabetes Centre at the Royal Adelaide Hospital according to the inclusion criteria when attending their scheduled appointment with a consultant. They will be double-blinded randomised to metformin or placebo. Allocation will be concealed by central randomisation by phone. Each subject will be assigned a unique identifier. Pharmacy staff will dispense the intervention in bottles labeled "metformin or placebo".
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
simple randomisation using computerised sequence generation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint(s)
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)

Funding & Sponsors
Funding source category [1] 285456 0
Hospital
Name [1] 285456 0
The Royal Adelaide Hospital
Address [1] 285456 0
ROYAL ADELAIDE
HOSPITAL
North Terrace
Adelaide SA 5000
Country [1] 285456 0
Australia
Primary sponsor type
Individual
Name
Professor Peter Clifton
Address
Baker IDI,
C/- University of South Australia
Level 5, Playford Building.
Adelaide
SA 5000
Country
Australia
Secondary sponsor category [1] 284310 0
Individual
Name [1] 284310 0
Dr Marianne Gillam
Address [1] 284310 0
Baker IDI,
C/- University of South Australia
Level 5, Playford Building.
Adelaide
SA 5000
Country [1] 284310 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286911 0
The Royal Adelaide Hospital Research Ethics Committee
Ethics committee address [1] 286911 0
THE ROYAL ADELAIDE
HOSPITAL
Research Ethics Committee
North Terrace
Adelaide SA 5000
Ethics committee country [1] 286911 0
Australia
Date submitted for ethics approval [1] 286911 0
Approval date [1] 286911 0
08/06/2012
Ethics approval number [1] 286911 0
RAH Protocol No: 120435

Summary
Brief summary
Metformin is a first line drug treatment in overweight patients with type 2 diabetes mellitus and has been used for decades in the treatment of these patients. People with type 2 diabetes mellitus can produce some insulin (which is different from patients with type 1 diabetes who need insulin to survive), but the body tissues are resistant to insulin leading to high blood glucose (sugar) because glucose in the blood is not absorbed. Many people with type 1 diabetes mellitus also have insulin resistance and in addition the insulin therapy that they need to survive often leads to weight gain.
Metformin works by decreasing blood glucose (sugar) levels by increasing insulin sensitivity in muscle cells, decreasing glucose production in the liver and delaying glucose uptake from the guts. Metformin also have beneficial effects on weight management and risk of stroke and heart attacks in people type 2 diabetes mellitus. Some studies have found evidence that metformin added to insulin therapy in type 1 diabetes mellitus leads to weight loss and reduced requirement for insulin, but the results are not conclusive. We are conducting this trial to investigate if metformin is useful as an addition to insulin therapy to lose weight, improve glucose control, reduce insulin dose requirement and improve blood lipids in people with type 1 diabetes mellitus.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33938 0
Address 33938 0
Country 33938 0
Phone 33938 0
Fax 33938 0
Email 33938 0
Contact person for public queries
Name 17185 0
Professor Peter Clifton
Address 17185 0
Baker IDI,
C/- University of South Australia
Level 5, Playford Building.
Adelaide
SA 5000
Country 17185 0
Australia
Phone 17185 0
61 8 8462 9702
Fax 17185 0
Email 17185 0
peter.clifton@bakeridi.edu.au
Contact person for scientific queries
Name 8113 0
Professor Peter Clifton
Address 8113 0
Baker IDI,
C/- University of South Australia
Level 5, Playford Building.
Adelaide
SA 5000
Country 8113 0
Australia
Phone 8113 0
61 8 8462 9702
Fax 8113 0
Email 8113 0
peter.clifton@bakeridi.edu.au