REduction of risk for cardiovascular events by treatment with metformin in patients with type 1 diabetes
- Conditions
- Type 1 diabetesMedDRA version: 16.1Level: PTClassification code 10067584Term: Type 1 diabetes mellitusSystem Organ Class: 10027433 - Metabolism and nutrition disordersTherapeutic area: Diseases [C] - Hormonal diseases [C19]
- Registration Number
- EUCTR2011-000300-18-DK
- Lead Sponsor
- HS Greater Glasgow and Clyde Board
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 120
Type 1 diabetes; age = 40 years; 7.0 = HbA1c < 10.0% (53-86 mmol/mol)
AND three or more of the following ten CVD risk factors:
(i) BMI = 27 kg/m2
(ii) current HbA1c > 8.0% (64 mmol/mol)
(iii) known CVD/ peripheral vascular disease
(iv) current smoker
(v) eGFR < 90 ml/ min/ 1.73 m2
(vi) micro- (or macro-) albuminuria [according to local assays and reference ranges]
(vii) hypertension (BP¬=140/ 90 mmHg; or established on antihypertensive treatment)
(viii) dyslipidaemia [total cholesterol=5.0 mmol/L (200 mg/dL); or HDL cholesterol<1.20 mmol/L (46 mg/dL) [men] HDL cholesterol<1.30 mmol/L (50 mg/dL) [women]; or fasting triglycerides=1.7 mmol/L (150 mg/dL); or established on lipid-lowering treatment
(ix) strong family history of CVD (at least one parent or sibling with myocardial infarction or stroke aged < 60 years)
(x) duration of diabetes > 20 years.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5
(i) eGFR < 45 ml/ min/ 1.73m2
(ii) woman of childbearing age not on effective contraception – see Appendix 4
(iii) pregnancy and/or lactation
(iv) Acute Coronary Syndrome within the last 3 months
(v) NYHA stage 3 or 4 heart failure
(vi) uncontrolled angina
(vi) suspected hypoglycaemia unawareness
(vii) impaired cognitive function/ unable to give informed consent
(viii) previous carotid surgery/ inability to capture adequte carotid images
(ix) gastroparesis
(x) history of lactic acidosis
(xi) other contraindications to metformin
-hepatic impairment
-known hypersensitivity to metformin
-acute illness (dehydration, severe infection, shock,
acute cardiac failure)
-suspected tissue hypoxia
(xii) Any coexistent life threatening condition including prior diagnosis of cancer within two years
(xii) history of alcohol problem or drug abuse
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess in a randomized controlled trial the effects of three years metformin added to titrated insulin therapy (towards target HbA1c 7.0%/ 53 mmol/mol) on progression of atheroma as measured by progression of averaged mean far wall common carotid artery intima-media thickness (cIMT) in adults with type 1 diabetes at risk of cardiovascular disease.;Secondary Objective: Change in (i) HbA1c; (ii) LDL cholesterol; (iii) albuminuria and estimated glomerular filtration rate; (iv) retinopathy stage (two-field photographs); (v) weight; (vi) insulin dose; (vii) endothelial function (in 50% of participants).;Primary end point(s): progression of averaged mean far wall common carotid artery IMT (CCA cIMT, measured in mm, at baseline, 12, 24 and 36 months). ;Timepoint(s) of evaluation of this end point: Baseline an hereafter annually
- Secondary Outcome Measures
Name Time Method Secondary end point(s): HbA1c; <br>(ii) LDL cholesterol; <br>(iii) albuminuria & estimated glomerular filtration rate <br>(iv) retinopathy stage (ETDRS stage = Early Treatment Diabetic Retinopathy Study); <br>(v) weight<br>(vi) insulin dose; <br>(vii) endothelial function <br>;Timepoint(s) of evaluation of this end point: Baseline and Annually hereafter for (i,ii,ii,v,vi,vii)<br>Baseline, year 1 and year 3 for (vii)<br>Baseline and year 3 for (iv)