Randomised, Double Blind, Placebo Controlled Trial of Angiotensin Converting Enzyme Inhibitors and Statins in the Prevention of Long Term Complications in Young People With Type 1 Diabetes
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 443
- 试验地点
- 2
- 主要终点
- Albumin creatinine ratio
研究概览
简要总结
The purpose of this study is to determine whether use of blood pressure lowering drugs, Angiotensin converting enzyme inhibitors (ACEIs) and blood fat (lipid) lowering drugs (statins) may have a place in the treatment of adolescents with diabetes and can help reduce serious long-term health problems in this population.
详细描述
Subjects will be recruited from a pre-screened population of 3,000 young people with T1D aged 10 to 16 years based on assessment of risk for future CVD and DN.
They will be randomised to a 2 x 2 factorial design contrasting the effects of ACEI, statins, or combination therapy to placebo over a maximum four year treatment period. Minimisation of variation in albumin excretion rate, gender, age, diabetes duration, HbA1c, total cholesterol and centre site will be undertaken at randomisation.
Analysis of the primary endpoint, change in albumin excretion will be undertaken on an intention to treat basis. Secondary analyses will be undertaken on the basis of 'as treated' allowing for variance in compliance and allowing for subjects who show substantial change in HbA1c levels. Additional analyses will be undertaken to assess changes in the secondary objectives and to assess the overall effect of the intervention on quality of life and health economics.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 10 Years 至 16 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 10 to 16 years.
- •T1D diagnosed for more than 1 year or C-peptide negative.
- •Centralised assessment of ACR based on six early morning urines deemed to be in upper tertile for risk after adjustment for age, gender, age at diagnosis and duration of disease.
排除标准
- •Non T1D, i.e. type 2 diabetes, insulin dependent diabetes related to monogenic disease, secondary diabetes.
- •ACR based on six early morning urines deemed to be at low risk for subsequent development of CVD or DN.
- •Pregnancy or unwillingness to comply with contraceptive advice and regular pregnancy testing throughout the trial.
- •Breast feeding
- •Severe hyperlipidaemia and family history data to support diagnosis of familial hypercholesterolaemia.
- •Established hypertension unrelated to DN.
- •Prior exposure to the investigational products, statins and ACEI.
- •Unwillingness/inability to comply with the study protocol.
- •Other co-morbidities considered unsuitable by the investigator (excluding treated hypothyroidism and coeliac disease).
- •Proliferative retinopathy.
- •Renal disease not associated with Type 1 Diabetes.
研究组 & 干预措施
Statin
Participants receive active statin and placebo ACE Inhibitor
干预措施: Statin (Drug)
Angiotensin-converting enzyme inhibitor
Participants receive active ACE Inhibitor and placebo statin
干预措施: ACE inhibitor (Drug)
Placebo
Participants receive placebo ACE Inhibitor and placebo statin
干预措施: Placebo (Drug)
Combination therapy
Participants receive both active ACE Inhibitor and active Statin
干预措施: Combination therapy (Drug)
结局指标
主要结局
Albumin creatinine ratio
时间窗: 2-4 years treatment duration
The area under the curve over time of log ACR per year, with standardisation for gender, age and duration of disease
次要结局
- Retinopathy(2-4 years treatment duration)
- Quality of Life and Health Economics(2-4 years treatment duration)
- Changes in CVD risk markers(2-4 yrs treatment duration)
- Changes in glomerular filtration rate (GFR)(2-4 years treatment duration)
研究者
David Dunger
Professor David Dunger
University of Cambridge