Phase 3 Study of Metformin in Adults With Type 1 Diabetes
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 493
- 试验地点
- 24
- 主要终点
- Change in Averaged Mean Far Wall Common Carotid Artery Intima-media Thickness (cIMT)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Metformin
Oral Metformin (as Glucophage 500mg x 2 bd) titrated from initial 500mg to target 2000mg daily
干预措施: Metformin (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Averaged Mean Far Wall Common Carotid Artery Intima-media Thickness (cIMT)
时间窗: 0, 12 months, 24 months, 36 months
Progression of averaged mean far wall common carotid artery intima media thickness IMT (mean cIMT) measured using B mode ultrasonography with a 7.0 MHz or higher broadband linear array transducer and concurrent recording of 3-lead electrocardiogram (ECG). Longitudinal images of the common carotid artery will be obtained at anterior, lateral and posterior angles at baseline, 12, 24 and 36 months using Meijer's arc to standardize the transducer angle.
次要结局
- Change in HbA1c(Baseline, Year 3)
- Change in LDL Cholesterol(Baseline, Year 3)
- Change in Estimated Glomerular Filtration Rate(Baseline, Year 1, Year 2, Year 3)
- Number of Participants With Retinopathy and at Least a 2 Stage Progression in Retinopathy From Baseline to 36 Months(Baseline, Year 3)
- Change in Weight(Baseline, Year 1, Year 2, Year 3)
- Change in Insulin Dose(Baseline, Year 1, Year 2, Year 3)
- Change in Endothelial Function(Baseline, Year 1, Year 3)
研究者
Prof John Petrie
Clinical Professor in Diabetic Medicine
University of Glasgow