Effect of Exenatide on 24h-UAER in Patients With Diabetic Nephropathy: a 24- Week Study
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 92
- 主要终点
- the percentage change of 24h-UAER(urinary albumin excretion rates) from baseline at Week 24
研究概览
简要总结
This is a multi-center, randomized, parallel study to evaluate effect of exenatide on 24h-UAER in patients with diabetic nephropathy.
Screening will be made to select eligible participants before intervention. The trial will include 2-week run-in period of stable doses of glargine plus lispro insulin and 24-week treatment period. After the run-in period, patients were randomly assigned to one of two groups for antihyperglycaemic therapies for a total of 24-weeks: glargine plus exenatide and continued glargine plus lispro insulin. The treatment of exenatide will be initiated by 5ug bid, and uptitrated to 10 ug bid after 4 weeks and then maintained at 10ug bid until the completion of the study. Lispro insulin will be initially treated according to the insulin dosage of previous antihyperglycaemic therapies, and further titrated up at 4-week intervals until to reach the target fasting blood glucose (FPG).
详细描述
Objective:
To evaluate effect of exenatide on 24-UAER in patients with diabetic nephropathy
Hypothesis:
Compared with glargine plus lispro group, at 24 weeks, glargine plus exenatide group can: 1) take more significant reduction of 24h-UAER; 2) take more reduction of ACR; 3) take more weight loss, blood pressure reduction; 4) take lower hypoglycemia incidence and less insulin dosage.
Primary endpoint： The proportion of reduction of 24h-UAER(urinary albumin excretion rates)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Provision of informed consent prior to any study specific procedures.
- •Diagnosed with type 2 diabetes with HbA1c ≥ 7.0% and ≤ 11.0% at screening (the result is valid for seven days).
- •Men and women (non-pregnant and using a medically approved birth-control method) aged from 18 to 80 at screening.
- •Body mass index (BMI) ≥18 and ≤35 kg/m
- •Blood Pressure (BP) ≥ 90/60mmHg and ≤160/100mmHg.
- •6.24h urinary albumin excretion rate (UAE) >0.3g/24h after 3 months treatment with several hypoglycemic agents (sulphonylureas, metformin, AG-inhibitor, meglitinides or insulin), ACEI/ARB and salt restriction(the result is valid for seven days).
- •7.eGFR >30ml/min(the result is valid for seven days).
排除标准
- •1．Women who are pregnant, intending to become pregnant during the study period, currently lactating females, or women of child-bearing potential not using highly effective, medically approved birth control methods.
- •Diagnosis or history of:
- •Type 1 diabetes mellitus, diabetes resulting from pancreatic injury or secondary forms of diabetes, eg, acromegaly or Cushing's syndrome.
- •Acute metabolic diabetic complications such as ketoacidosis or hyperosmolar coma within the past 6 months.
- •Previous treatment with any Thiazolidinediones (TZDs), dipeptidyl peptidase-4 (DPP4) inhibitor or GLP-1 receptor agonists within the past 3 months.
- •History of hypersensitivity reaction (e.g., anaphylaxis, angioedema, exfoliative skin conditions) to exenatide.
- •Blood amylase and/or lipase > 2 times the upper limit of the normal (ULN) laboratory range.
- •Hyperkalemia (K+>5.5mmol/L).
- •eGFR <30ml/min/1.73m
- •Patients without diabetic retinopathy.
- •Triglycerides (fasting) > 4.5 mmol/L (400 mg/dL) at screening or within 4 weeks prior to screening (by local laboratory).
- •Patients with clinically apparent liver disease characterized by ALT or AST > 3ULN confirmed on two consecutive measurements (by local laboratory) within 4 weeks prior to screening period.
- •Significant cardiovascular history within the past 3 months prior to screening defined as: myocardial infarction, coronary angioplasty or bypass graft(s), valvular disease or repair, unstable angina pectoris, transient ischemic attack, or cerebrovascular accident.
- •Congestive heart failure defined as New York Heart Association (NYHA) class III or IV.
- •History of chronic pancreatitis or idiopathic acute pancreatitis.
- •History of medullary thyroid carcinoma.
研究组 & 干预措施
Lispro
Patients are treated with Glargine (Lantus, Sanofi-Aventis), the dosage is initiated according to the previous treatment plan and weight of the patients, injection before bed time, titration following FPG <7.2mmol/L and >4.4mmol/L.
干预措施: Lispro (Drug)
Exenatide
Patients are treated with Glargine (Lantus, Sanofi-Aventis), the dosage is initiated according to the previous treatment plan and weight of the patients, injection before bed time, titration following FPG <7.2mmol/L and >4.4mmol/L.
干预措施: Exenatide (Drug)
结局指标
主要结局
the percentage change of 24h-UAER(urinary albumin excretion rates) from baseline at Week 24
时间窗: from baseline at Week 24
the percentage change of 24h-UAER=(24h-UAERweek24 - 24h-UAERbaseline)/ 24h-UAERbaseline
次要结局
- Change in 24h-UAER(from baseline at Week 24)
- Change in Weight(from baseline at Week 24)
- Change in Blood pressure(from baseline at Week 24)
- the percentage change of ACR(from baseline at Week 24)
- Change in FPG(from baseline at Week 24)
- Change in HbA1c(from baseline at Week 24)
研究者
Yaoming Xue
Department of Endocrinology and Metabolism
Nanfang Hospital, Southern Medical University