REducing With MetfOrmin Vascular Adverse Lesions in Type 1 Diabetes (REMOVAL)

• Status: Completed
• Trial end date: 2017-04-18
• Target enrollment: 0
• Participant gender: All

Summary

The trial is conducted in the United Kingdom (UK), Australia, Canada, Denmark and the Netherlands. The aim is to test whether 3 years treatment with metformin added to titrated insulin therapy (towards target HbA1c 7.0%/53 mmol/mol) reduces atherosclerosis, as measured by progression of carotid intima-media thickness (cIMT), in adults with confirmed type 1 diabetes aged 40 years and over at increased risk for cardiovascular disease.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Glasgow
• Collaborators: Imperial College London; Itamar-Medical, Israel; Juvenile Diabetes Research Foundation; Maastricht University Medical Center; Merck Serono S.A., Geneva; NHS Greater Glasgow and Clyde; Steno Diabetes Center; Steno Diabetes Center Copenhagen; University of Dundee; University of Melbourne; University of Western Ontario, Canada; University of Wisconsin, Madison
• Treatments: Metformin

Criteria

Inclusion Criteria:

• Type 1 Diabetes for five years or more*

• Age 40 years or above

• 7.0 =< HbA1c <10.0% (53 - 86 mmol/mol)

AND 3 or more of the following ten CardioVascular Disease (CVD) risk factors:

• BMI >27 kg/m^2

• Current HbA1c >8.0% (64 mmol/mol)

• Known CVD/peripheral vascular disease

• Current smoker

• Estimated glomerular filtration rate (eGFR) <90 ml/min per 1.73 m^3

• Confirmed micro- or macroalbuminuria [according to local assays and reference ranges]

• Hypertension (BP >=140/90 millimeters of mercury (mmHg) or established on antihypertensive treatment)

• Dyslipidaemia [total cholesterol >=5.0 mmol/L (200 mg/dL);OR HDL cholesterol <1.20 mmol/L (46mg/dL) [MEN]; OR <1.30 mmol/L (50 mg/dL) [WOMEN]; or triglycerides >=1.7 mmol/L (150mg/dL); or established on lipid-lowering treatment)]

• Strong family history of CVD (at least one parent, biological aunt/ uncle, or sibling with myocardial infarction or stroke aged <60 years)

• Duration of diabetes > 20 years

Exclusion Criteria:

• eGFR < 45 ml/min/1.73m2

• woman of childbearing age not on effective contraception

• Pregnancy and/or lactation

• Acute coronary syndrome or Stroke/Transient Ischaemic Attack within the last three months

• NYHA stage 3 or 4 heart failure

• Significant hypoglycaemia unawareness

• Impaired cognitive function/ unable to give informed consent

• Previous carotid surgery/ inability to capture adequate carotid images

• Estimated glomerular filtration < 45ml/min/1.73m^2 (MDRD)

• Gastroparesis

• History of lactic acidosis

• Other contraindications to metformin (hepatic impairment, known hypersensitivity to metformin, acute illness such as dehydration, severe infection, shock, acute cardiac failure or suspected tissue hypoxia)

• Any coexistent life threatening condition including prior diagnosis of cancer within two years

• History of alcohol problem or drug abuse