Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12611000148976
Ethics application status
Approved
Date submitted
8/02/2011
Date registered
8/02/2011
Date last updated
2/07/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
Does Metformin improve vascular function in youth with Type 1 diabetes
Scientific title
Does Metformin improve vascular function in youth with Type 1 Diabetes
Secondary ID [1] 253462 0
REC2327/12/13
Universal Trial Number (UTN)
U1111-1119-3513
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 diabetes 261015 0
Obesity 261016 0
Vascular health 261017 0
Condition category
Condition code
Metabolic and Endocrine 259153 259153 0 0
Diabetes
Cardiovascular 259154 259154 0 0
Diseases of the vasculature and circulation including the lymphatic system
Diet and Nutrition 259279 259279 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Administration of Metformin tablets: If weight > 60kg - 500mg daily for 2 weeks increased to 1g twice daily over the following 6 weeks, then 1g twice daily for 12 months. For weight < 60kg - 500mg daily for 2 weeks then 500mg twice daily for 6 months. Dietary advice - session with a dietician (1 hour) at the commencement of the study and a review at 3 months (1 hour) a written information sheet will be provided. Activity data will be collected prior each dietary assessment using a SensWear device (external device worn over the upper arm - like a watch) for 5 days.
Intervention code [1] 257905 0
Prevention
Intervention code [2] 257999 0
Treatment: Drugs
Comparator / control treatment
placebo tablet containing: sodium starch glycolate (type A0, Povidone, maize starch, magnesium sterate, silica, colloidal anhydrous, hypromellose, macrogol 6000, purified talc, titanium dioxide. The tablets are identical to the metformin 500mg tablet aside from the absence of metformin. The placebo group also receive dietary advice

There will be an additional baseline comparator group of non Type 1 Diabetes participants. They will be recruited based on the same criteria as the T1D population (but will not have the diagnosis of T1D). This population will not receive the intervention and will have a single baseline assessment.
Control group
Placebo

Outcomes
Primary outcome [1] 262079 0
Vascular function (flow mediated dilatation and Glyceryl trinitrate induced dilatation)
Timepoint [1] 262079 0
0, 3, 6, 12 months
Secondary outcome [1] 273113 0
serum adiponectin/leptin ratio
Timepoint [1] 273113 0
0, 3, 6, 12
Secondary outcome [2] 273114 0
Waist circumference
Timepoint [2] 273114 0
0, 3, 6, 12 months
Secondary outcome [3] 273115 0
Body mass index
Timepoint [3] 273115 0
0, 3, 6, 12 months
Secondary outcome [4] 273116 0
Body composition assessed by DEXA (nuclear medicine study)
Timepoint [4] 273116 0
0, 12 months
Secondary outcome [5] 273117 0
Insulin requirements - calculated from total daily dose of insulin
Timepoint [5] 273117 0
0, 3, 6, 12 months
Secondary outcome [6] 273118 0
whole blood HbA1c
Timepoint [6] 273118 0
0, 3, 6, 12 months
Secondary outcome [7] 273119 0
Fasting serum Lipids
Timepoint [7] 273119 0
0, 3, 6, 12 months
Secondary outcome [8] 273137 0
serum HsCRP
Timepoint [8] 273137 0
0, 3, 6, 12 months
Secondary outcome [9] 276521 0
Retinal photograph
Timepoint [9] 276521 0
0, 12 months

Eligibility
Key inclusion criteria
Body Mass Index > 50th centile for age Type 1 Diabetes duration greater than 1 year and insulin requirements > 0.5 units/kg/day
Baseline comparator group: Body Mass Index > 50th centile for age
Minimum age
8 Years
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
non type 1 diabetes Severe hypoglycaemic episode in the previous 6 months Recurrent Diabetic ketoacidosis (> 2 episode in the previous year) History of smoking OR serum cotinine level > 28 nmol/L Other serious comorbidities (eg liver and renal disease) Contraindications to metformin therapy (hypersensitivity, renal or liver dysfunction, Vitamin B12 deficiency) Inability to abstain from alcohol Pregnancy or breastfeeding Subjects already taking metformin, oral contraceptives, antihypertensives, multivitamins or statins

Baseline comparator group: type 1 diabetes or non type 1 diabetes History of smoking OR serum cotinine level > 28 nmol/L Other serious comorbidities (eg liver and renal disease) Pregnancy or breastfeeding Subjects already taking metformin, oral contraceptives, antihypertensives, multivitamins or statins

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Each participant will be assigned a unique identifier. Pharmacy staff will dispense the intervention (either metformin or placebo) in bottles which do not specify whether they contain metofrmin or placebo (the label reads "metformin or placebo" and could contain either).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using computer sofware sequence generation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
9/02/2011
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
76
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 722 0
Womens and Childrens Hospital - North Adelaide
Recruitment hospital [2] 1196 0
Flinders Medical Centre - Bedford Park

Funding & Sponsors
Funding source category [1] 258442 0
Commercial sector/Industry
Name [1] 258442 0
Paediatric Endocrine Research Grant (Pfizer Australia)
Country [1] 258442 0
Australia
Funding source category [2] 258456 0
Charities/Societies/Foundations
Name [2] 258456 0
WCH foundation
Country [2] 258456 0
Australia
Primary sponsor type
Individual
Name
Alexia Pena
Address
Endocrine Department
72 King William Street
Women's and Children's Hosptial
North Adelaide SA
5006
Country
Australia
Secondary sponsor category [1] 257588 0
Individual
Name [1] 257588 0
Prof Jennifer Couper
Address [1] 257588 0
Endocrine Department
72 King William Street
Women's and Childrens Hospital
North Adelaide SA
5006
Country [1] 257588 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 260430 0
Children, Youth and Women's Health Service (CYWHS) Human Research Ethics Committee
Ethics committee address [1] 260430 0
Women's and Children's Hospital
Research Secretariat
72 King William Street
North Adelaide
SA 5006
Ethics committee country [1] 260430 0
Australia
Date submitted for ethics approval [1] 260430 0
Approval date [1] 260430 0
25/01/2011
Ethics approval number [1] 260430 0
2327/13/12

Summary
Brief summary
Cardiovascular disease is the leading cause of mortality in type 1 diabetes (T1D). Prevention of vascular complications of diabetes requires strategies that begin early in the disease process. Risk factors in childhood track into adulthood and correlate with early markers of atherosclerosis such as vascular endothelial and smooth muscle function.

We have shown that children and adolescents with type 1 diabetes have detectable endothelial and smooth muscle dysfunction that relate to body mass index (BMI). A significant number of youth with T1D are also overweight with insulin resistance. Metformin reduces insulin requirements and weight gain in type 1 diabetes. In type 2 diabetes Metformin substantially reduces risk of cardiovascular events and improves endothelial function. However there are no studies of cardiovascular outcomes or their earlier cardiovascular markers in type 1 diabetes despite the increasing prevalence of overweight status in this population and the fact that this is a major modifiable risk factor for cardiovascular disease.

Determining the effect of Metformin on vascular function in overweight youth with type 1 diabetes in a double blind randomized placebo controlled parallel trial will provide additional strategies to intervene in early in the process of atherosclerosis.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32126 0
Dr Alexia Pena
Address 32126 0
72 King William St
North Adelaide SA
5006
Country 32126 0
Australia
Phone 32126 0
+61 8 8161 7000
Fax 32126 0
Email 32126 0
[email protected]
Contact person for public queries
Name 15373 0
Dr Dr Alexia Pena
Address 15373 0
Endocrine Department
Women's and Children's Hosptial
72 King William Street
North Adelaide SA
5006
Country 15373 0
Australia
Phone 15373 0
+61 8 8161 8134
Fax 15373 0
+61 8 8161 7759
Email 15373 0
[email protected]
Contact person for scientific queries
Name 6301 0
Dr Dr Alexia Pena
Address 6301 0
Endocrine Department
Women's and Children's Hosptial
72 King William Street
North Adelaide SA
5006
Country 6301 0
Australia
Phone 6301 0
+61 8 81618134
Fax 6301 0
+61 8 8161 7759
Email 6301 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Current supporting documents:


Updated to:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
23188Study protocol   

Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseEarly atherosclerosis is associated with retinal microvascular changes in adolescents with type 1 diabetes.2018https://dx.doi.org/10.1111/pedi.12764
EmbaseMacrovascular disease and risk factors in youth with type 1 diabetes: time to be more attentive to treatment?.2018https://dx.doi.org/10.1016/S2213-8587%2818%2930035-4
EmbaseEffect of metformin on vascular function in children with type 1 diabetes: A 12-month randomized controlled trial.2017https://dx.doi.org/10.1210/jc.2017-00781
N.B. These documents automatically identified may not have been verified by the study sponsor.