Investigating the Links Between Microbiota Composition and Variability Observed in the Pharmacological Response to Immunosuppressive Therapies in Kidney Transplant Patients.
试验速览
- 阶段
- 不适用
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Study of the links between immunosuppressive drugs pharmacology and intestinal microbiota composition
研究概览
简要总结
Solid organ transplantation is the treatment of choice for patients suffering from end-stage organ disease, including for chronic kidney failure. The implementation of effective immunosuppressive therapies has already significantly improved the prognosis for graft survival. However, these therapies are often associated with considerable inter- and intra-individual variability both in terms of response or in terms of pharmacokinetics. Innovative approaches must be considered, such as studying the involvement of intestinal microbiota in the pharmacology of these drugs.
The general aim of the study is therefore to relate the variabilities observed in the pharmacology (mainly pharmacokinetics) of immunosuppressive drugs used in renal transplantation (tacrolimus and mycophenolate mofetil) and the composition of the intestinal microbiota of renal transplant patients.
详细描述
Solid-organ transplantation often requires the implementation of a lifelong immunosuppressive therapy. A combination of tacrolimus (TAC), mycophenolate mofetil (MMF), together with steroids is currently used in over 60% of cases. In some patients however, these therapies are associated with high levels of variability, either in terms of response to treatments or in terms of pharmacokinetics, which remains unexplained. To address the issue, new approaches are being considered, in this study we will investigate the involvement of the intestinal microbiota in the pharmacology of these drugs. This is a particularly promising avenue for drugs with a low therapeutic index and large intra- and inter-individual pharmacokinetic variabilities such as tacrolimus and mycophenolate mofetil. Despite promising preliminary data for tacrolimus, the influence of the gut microbiota in these pharmacokinetic variabilities remains unclear, even less data are available about the involvement of the microbiota in the pharmacokinetics of mycophenolate mofetil.
We expect that this study will produce additional information on the effect of immunosuppression drugs on gut microbiota, and the relationship between microbiota composition and variabilities.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients within 1 to 8 years post transplantation
- •Aged between 18 and 75 years old
- •Patients receiving tacrolimus and mycophenolate mofetil as part of their immunosuppressive therapy
- •French speaking
- •BMI between 18 and 30.
排除标准
- •Use of tobacco
- •Potential Alcohol problems (less than two positive answers to the CAGE questionnaire)
- •Use of antibiotic medication within 3 months of the sample collection
- •Use of laxative medication within 2 weeks of the sample collection
- •Use of anti-fungal medication within 2 weeks of the sample collection
- •Pregnant or lactating patients.
研究组 & 干预措施
Tacrolimus / Mycophenolate Mofetil
All patients receive maintenance immunosuppressive treatment of tacrolimus in combination with Mycophenolate Mofetil.
干预措施: Tacrolimus (Drug)
结局指标
主要结局
Study of the links between immunosuppressive drugs pharmacology and intestinal microbiota composition
时间窗: 24 months
The general aim of the study is to relate the variabilities observed in the pharmacology (mainly pharmacokinetics) of immunosuppressive drugs used in kidney transplantation (tacrolimus and mycophenolate mofetil) and the composition of the intestinal microbiota of these patients.
次要结局
- Identify links between oral dosage and concentrations found in feces(18 months)
- Identify genetic factors underlying the links between microbiota and Tacrolimus/Mycophenolate Mofetil(18 months)
- Tacrolimus concentrations and microbiota(18 months)
- Tacrolimus concentrations and genetic polymorphisms(18 months)
- Tacrolimus concentration and demographics(18 months)
- Mycophenolate Mofetil concentration and microbiota(18 months)
- Mycophenolate Mofetil concentration and polymorphisms(18 months)
- Mycophenolate Mofetil concentration and demographics(18 months)
- Investigate potential markers of kidney function in metabolites(18 months)