An Open Label, Randomized, Two-Period Crossover Study to Evaluate the Safety and Efficacy of the Addition of Alanyl-Glutamine-Dipeptide to Dialysis Solutions in Peritoneal Dialysis (PD) (Ala-Gln in PD)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Primary Endpoint: Total heat shock expression in peritoneal cells from dialysate samples;
研究概览
简要总结
Peritoneal dialysis (PD) is a cost effective and safe form of renal replacement therapy in patients suffering from end stage renal disease.
However currently available PDF (peritoneal dialysis fluids) are not biocompatible for the peritoneal cavity and its cells. Acute cytotoxic effects of the majority of the current glucose-based PDF are caused by low pH, lactate, high glucose and its degradation products (GDP).
Toxic effects of PDF can thus be extended to suppression of mesothelial HSR (heat shock reactions) following PDF exposure resulting in increased susceptibility of mesothelial cells against PDF exposure: PDF inherent stress factors fail to adequately induce HSP as effectors of the cellular stress response - the adequate HRS rather seems to be blocked.
Hence, therapeutic approaches to activate and enhance the HSR will reduce peritoneal damage and organ failure and improve the survival of organisms.
Preclinical results demonstrated that supplementation of PDF with pharmacological doses of alanyl-glutamine restored HSP expression and increased the resistance of mesothelial cells in in-vitro models of PD and preserved peritoneal integrity in in-vivo models of PD.
After these positive preclinical results, this study shall now clarify, whether the addition of alanyl-glutamine to the most commonly used glucose-based PDF is safe and tolerable. Therefore PDFs will be drained in a randomized cross-over study. Main outcomes measures will be total HSP expression in peritoneal cells and changes of the peritoneal transport kinetics and the presence/absence/severity of side effects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent prior to any study-mandated procedure
- •Male and female patients aged ≥ 19 years old
- •Chronic renal failure; 2 months stable on PD
- •no peritonitis within the previous 2 months
- •Without severe concomitant disease
- •Negative pregnancy test in female patients of childbearing potential and adequate contraception in female patients of childbearing age
排除标准
- •Known hypersensitivity to study medication
- •Treatment with another investigational drug within 1 month prior to start of study medication
- •Malignancy requiring chemotherapy or radiation
- •Pregnancy or nursing,
- •Presumed non-compliance
- •Limited efficacy of peritoneal dialysis due to anatomical anomalies or severe intra-abdominal adhesions
- •Clinical significant inflammatory parameters
- •Less than 50 kg body weight
- •Immunosuppressive therapy
研究组 & 干预措施
Arm A
Arm A includes 14 patients. In treatment period 1, arm A receives standard PDF with the interventional drug alanyl-glutamine-dipeptide as add-on. As it is a cross-over study design, in treatment period 2, group A receives standard PDF without add-on.
干预措施: Dipeptiven (Alanyl-glutamine-dipeptide) (Drug)
Arm B
Arm B includes 14 patients who in treatment period 1 receive standard PDF without the investigational drug. As it is a cross-over study design, in treatment period 2 arm B receives standard PDF with alanyl-glutamine-dipeptide as add-on.
干预措施: Dipeptiven (Alanyl-glutamine-dipeptide) (Drug)
结局指标
主要结局
Primary Endpoint: Total heat shock expression in peritoneal cells from dialysate samples;
时间窗: up to 70 days
In this study, an increase of total heat shock protein expression will be detected in cells from the peritoneal effluent at 240 min by staining of the cytospin and by Western blot analysis of the cellular pellet of the effluent. Total heat shock expression from dialysate samples is calculated in percent.
次要结局
- Clinical PET-test to measure specific transport kinetics in peritoneal cells (creatinine, urea, sodium, potassium, phosphor, glucose, protein)(up to 70 days)
- Cell number in peritoneal effluent;(up to 70 days)
- cytokines (IL-6, IL-8, TNFα);(up to 70 days)
- Cell function (phagocytosis and cytokine production)(up to 70 days)
- Morphology of peritoneal cells from effluent (cell culture)(up to 70 days)
- Biomarker CA125(up to 70 days)
- Tolerability/safety endpoints: No. and severity of AEs(up to 70 days)
研究者
Christoph Aufricht
Ao.Univ.-Prof. Dr.med.univ.
Medical University of Vienna