Effects on Insulin Secretion and Sensitivity of Two Different Formulations Tacrolimus - Prograf® and Advagraf®
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- The primary objective is to compare insulin secretion (Secr2.phase) between the two different formulations of Tac.
研究概览
简要总结
One of the main side-effects of tacrolimus in solid organ transplanted patients is post transplant diabetes mellitus (PTDM). It is not known if different pharmacokinetic properties influence the risk of developing PTDM. It is possible that it either is high peak concentrations of high overall systemic exponation that is responsible for the effect on insulin secretion. With the new slow-release formulation of tacrolimus (Advagraf) a different pharmacokinetic profile is introduced to patients and it is of interest to investigate if this affects insulin secretion and insulin sensitivity of patients.
Hypothesis: The pharmacokinetic profile of tacrolimus affects the insulin secretion in renal transplant recipients.
详细描述
Study objectives
The primary objective is to compare insulin secretion (Secr2.phase) between the two different formulations of Tac.
Secondary objectives are to compare the effect of the two formulations on Secr1.phase, insulin sensitivity and to investigate possible associations with individual systemic tacrolimus exposures.
Study design
Twenty adult kidney transplanted patients treated with Prograf® twice daily or Advagraf® once daily will be included in the study. Eligible patients may be included in a stable posttransplant phase (no Tac dose adjustments or acute rejection episodes the preceding 2 weeks). A 3-hour hyperglycaemic clamp will be performed while patients are treated with their standard Tac formulation and repeated 4-6 weeks after switching to the alternative Tac formulation. The clamp investigation will be done after administration of the morning dose of Tac. Samples for measurement of Tac whole blood concentrations will be drawn for all patients up to 24 hours after morning Tac dosing. It is not mandatory for all patients to perform full 24 hour pharmacokinetic investigations.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Renal transplant recipients on stable Tac based immunosuppressive therapy.
- •18 years of age or older.
- •Stable prednisolone dose of 5 mg/day or less.
- •S-creatinine below 150 umol/L.
- •Signed informed consent.
排除标准
- •Acute rejection episodes within the last 2 weeks prior to inclusion.
- •Changes in Tac dosing within the last 2 weeks prior to inclusion.
- •Diabetes mellitus (WHO criteria).
- •Pregnant or nursing mothers or women of childbearing potential without acceptable contraception strategy.
- •Concomitant treatment with: diltiazem, verapamil, fenytoin, carbamazepine, fluconazole, ketoconazole, voriconazole, erythromycin, clarithromycin.
- •Patients treated with investigational drugs.
研究组 & 干预措施
Prograf
Patients are treated until steady-state conditions with Prograf and then investigated with clamp
干预措施: Tacrolimus (Drug)
Advagraf
The patients are treated with Advagraf until steady-state conditions and then investigated with clamp
干预措施: Tacrolimus (Drug)
结局指标
主要结局
The primary objective is to compare insulin secretion (Secr2.phase) between the two different formulations of Tac.
时间窗: 1 month
Insulin secretion is investigated by hyperglycemic clamp
次要结局
- insulin sensitivity(1 month)
- Secondary objectives are to compare the effect of the two formulations on Secr1.phase,(1 month)
研究者
Anders Åsberg
Study leader
University of Oslo School of Pharmacy