The Effect of Rimonabant Treatment on Cardiovascular Risk Factors in Renal Transplant Recipients -- Pilot Safety Study
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Effect of rimonabant on cylosporine/tacrolimus bioavailablility
研究概览
简要总结
The major cause of premature death in renal transplant recipients is cardio-vascular disease. In addition, obesity is becoming a major problem in this patient population. Rimonabant does not only seem to have weight reducing properties but also weight reduction independent effects on insulin sensitivity and endothelial function, two important cardio-vascular risk factors. Rimonabant therefore is an interesting drug for the treatment of transplanted patients. Present data also indicate that rimonabant does not interact with essential immunosuppressive drugs (CsA and Tac) indicating that it most probably is safe to administer to this patient population. However this needs to be investigated in a proper manner.
详细描述
Renal transplant recipients are treated with life-long immunosuppressive therapy in order to prevent acute rejection episodes. The calcineurin inhibitors (CsA and Tac) are the back-bones in the immunosuppressive treatment and they have a very narrow therapeutic index. It is therefore essential to assure that new drug to be used in transplanted patients do not interact with CsA and Tac. Even though rimonabant is metabolized via the same enzyme as CsA and Tac (CYP3A4) previous in vitro and in vivo studies with relevant probe drugs in healthy volunteers do not indicate the presence of any relevant pharmacokinetic interaction. However, to be absolutely sure that it is safe to administer rimonabant in transplanted patients a 12-hour pharmacokinetic interaction investigation is included for 16 patients in the present pilot study (8 patients on CsA and 8 patients on Tac).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 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 recipient with stable renal function (less than 20% deviation in serum creatinine the last 2 months).
- •Renal transplant recipient currently on CsA or Tac and prednisolone based immunosuppression.
- •BMI > 30 kg/m2 or >27 kg/m2 in combination with one or more cardio-vascular risk factors.
- •> 18 years of age.
- •Male patient, or female patient without childbearing potential (surgically sterilized or postmenopausal) or, if female of childbearing potential, is not lactating, has a negative pregnancy test at screening and is willing to utilize an effective method of contraception throughout the study period and for 90 Days following discontinuation of the Study Drugs.
- •Signed informed consent.
排除标准
- •Diabetes mellitus
- •Severe liver disease.
- •Depressive-, anxiety- or sleeping disorders.
- •Estimated GFR < 25 ml/min.
- •Epilepsy.
- •Skin disorders that may influence laser Doppler flowmetry investigations.
- •Pregnant or nursing mothers.
- •Concomitant treatment with CYP3A4 inhibitors (www.cyp450.no) with interaction potential according to the investigator.
研究组 & 干预措施
CsA
Investigation of systemic exposure of cyclosporine before and after 2 moths of co-adminiastration of rimonabant.
干预措施: cyclosporine A (Drug)
Tac
Investigation of systemic exposure of tacrolimus before and after 2 moths of co-adminiastration of rimonabant.
干预措施: tacrolimus (Drug)
结局指标
主要结局
Effect of rimonabant on cylosporine/tacrolimus bioavailablility
时间窗: 2 months
次要结局
- Effect of rimonabant on insulin sensitivity(2 months)