Pilot Study of In Vitro Immunosuppressive Effects of Mycophenolate Mofetil and Valganciclovir in Kidney Transplant Recipients
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 4
- 主要终点
- The primary endpoint of this study is the analysis of immune responsiveness in vitro in patients before and after routine cessation of VGCV.
研究概览
简要总结
Valganciclovir (VGCV) has recently been approved by the Food and Drug Administration (FDA) for the treatment and prevention of cytomegalovirus (CMV) retinitis in HIV patients. It is under review for the prevention of CMV disease following organ transplantation. Mycophenolate mofetil (MMF), the morpholinoethyl ester of mycophenolic acid (MPA) is currently the most widespread used immunosuppressant in kidney transplantation. These drugs exerts their effects by blocking the production of DNA primarily in lymphocytes.
Recent studies have suggested that combining both MMF and GCV in vitro may have a beneficial effect on the treatment of CMV infections. However, the effect of these two drugs in combination on the effects of the immune system both in vitro and in vivo have not been studied. Preliminary studies in our lab show that a combination of these two drugs have an additive effect on the level of immunosuppression of both the growth and differentiation of progenitor bone marrow cells as well as lymphocyte proliferation.
This study is designed to test patients degree of immune reactivity both on and off VGCV when used in combination with MMF. Patients will have blood drawn as several time points and an immune assay will be performed to show if VGCV when used in combination with MMF exerts immunosuppressive effects.
详细描述
Recruitment and screening of subjects will be performed between 4 and 8 weeks after transplantation at which time consent will be obtained. Per clinical standard of care at Indiana University, VGCV is routinely stopped at 12 weeks post transplantation. At week 10 and the day of discontinuation of their prophylaxis the patients will be seen by the study physician. The subjects will also be seen at 2 and 4 weeks after discontinuing VGCV. At each study visit, the subject will have a limited history and physical (H&P) performed, one 3ml light green top (lithium heparin) tube, one 3ml dark green top (sodium heparin) tube, and one 5ml purple top (EDTA) tube will be obtained by phlebotomy during their regularly scheduled blood draw times. This blood will then be used for the Cylex® assay, Flow cytometry and MMF and GCV trough level. The patient's complete blood count and differential as well as drug levels, and medication dosages will be recorded. This information will be used for assure that Cylex® results are not being influenced by changes in immunosuppressive drug levels. The complete blood count and differential will be used to determine absolute neutrophil counts. After the week sixteen visit, the subjects will have completed the protocol. Pregnancy tests will not be performed as patients are not directly receiving any treatment secondary to this study. Flow cytometry will be performed to measure absolute CD4 counts, CD4/CD8 ratios, and look at several activation markers on lymphocytes.
Signed IRB approved informed consent must be obtained from all subjects prior to screening assessments. The following evaluations will be performed prior to initiation of phlebotomy for purposes of this study.
Medical history including age, gender, race, and renal disease, immunosuppressive regimen including dose, level and use of antibody treatment at time of transplant will be noted.
Physical examination including: vital signs, cardiac, and lung evaluation.
Laboratory testing which will be performed as part of standard of care because of the transplant are:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Diagnostic
- 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
- •>18 years of age
- •Primary kidney transplant
- •MMF included as part of baseline immunosuppression
- •On valganciclovir for CMV prophylaxis. The dose will vary based on renal function but the standard dose is 900 mg per day
- •No prior episodes of rejection
- •On a stable dose of immunosuppressive medications -
排除标准
- •Previous or multiple transplant patients (e.g. second kidney or simultaneous kidney pancreas patient)
- •Uncontrolled or recurrent infections.
- •Psychiatric disorder -
结局指标
主要结局
The primary endpoint of this study is the analysis of immune responsiveness in vitro in patients before and after routine cessation of VGCV.
次要结局
- Secondary endpoints of this study are the analysis of absolute neutrophil count before and after routine cessation of VGCV. This will be obtained from the patient's complete blood count and differential.