Mitochondrial Dysfunction in Chronic Kidney Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Phosphocreatine (PCR) Recovery Time After Knee Extension Assessed by 31 Phosphorus Magnetic Resonance Spectroscopy (31P-MRS)
研究概览
简要总结
The overarching goal of this study is to determine the role of chronic kidney disease and the activation of the kallikrein-kinin system during hemodialysis on the development of mitochondrial dysfunction; the investigators will measure mitochondrial function using the gold standard method, 31-phosphorus magnetic resonance spectroscopy.
The investigators will test the hypothesis that endogenous bradykinin promotes mitochondrial dysfunction in patients undergoing hemodialysis. The investigators will first perform a randomized, placebo-controlled, double-blind, cross-over study measuring the effect of Icatibant (HOE-140), a bradykinin B2 receptor blocker, on mitochondrial function.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 78 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients who have been on maintenance hemodialysis for at least 6 months
排除标准
- •History of functional transplant less than 6 months prior to study
- •Use of immunosuppressive drugs within 1 month prior to study
- •History of active connective tissue disease
- •History of acute infectious disease within one month prior to study
- •AIDS (HIV seropositivity is not an exclusion criteria)
- •History of myocardial infarction or cerebrovascular event within 3 months
- •Advanced liver disease
- •Gastrointestinal dysfunction requiring parental nutrition
- •Active malignancy excluding basal cell carcinoma of the skin
- •Ejection fraction less than 30%
- •Anticipated live donor kidney transplant
- •Pregnancy, breast-feeding or child-bearing potential
- •History of poor adherence to hemodialysis or medical regimen
- •Subjects with cardiac pacemaker, artificial heart valve, any metallic implant, permanent tattoo, or any retained foreign metallic bodies that are contraindicated in magnetic resonance imaging.
- •Inability to provide consent
研究组 & 干预措施
Icatibant then Placebo
Icatibant will be intravenously infused at a rate of 50 ug/kg/h for 1 hour prior to the initiation of dialysis and continue through hemodialysis (4 hours)
1 week washout
Placebo will be intravenously infused at the same rate of Icatibant (50 ug/kg/h) for 1 hour prior to the initiation of dialysis and continue through hemodialysis (4 hours)
干预措施: Icatibant (Drug)
Icatibant then Placebo
Icatibant will be intravenously infused at a rate of 50 ug/kg/h for 1 hour prior to the initiation of dialysis and continue through hemodialysis (4 hours)
1 week washout
Placebo will be intravenously infused at the same rate of Icatibant (50 ug/kg/h) for 1 hour prior to the initiation of dialysis and continue through hemodialysis (4 hours)
干预措施: Placebo (Drug)
Placebo then Icatibant
Placebo will be intravenously infused at the same rate of Icatibant (50 ug/kg/h) for 1 hour prior to the initiation of dialysis and continue through hemodialysis (4 hours)
1 week washout
Icatibant will be intravenously infused at a rate of 50 ug/kg/h for 1 hour prior to the initiation of dialysis and continue through hemodialysis (4 hours)
干预措施: Icatibant (Drug)
Placebo then Icatibant
Placebo will be intravenously infused at the same rate of Icatibant (50 ug/kg/h) for 1 hour prior to the initiation of dialysis and continue through hemodialysis (4 hours)
1 week washout
Icatibant will be intravenously infused at a rate of 50 ug/kg/h for 1 hour prior to the initiation of dialysis and continue through hemodialysis (4 hours)
干预措施: Placebo (Drug)
结局指标
主要结局
Phosphocreatine (PCR) Recovery Time After Knee Extension Assessed by 31 Phosphorus Magnetic Resonance Spectroscopy (31P-MRS)
时间窗: Up to 2 hours after completion of drug infusion
Mitochondria function will be evaluated using 31P-MRS, which evaluates the concentration of phospho-creatine (PCr) and other phosphate-energy carrier molecules. After basal measurements, subjects will be asked to perform 90 seconds of knee extension followed by 4 minutes of rest. The exercise/rest cycle will be repeated 3 times. Magnetic resonance spectra will be used to calculate concentrations of inorganic phosphate (Pi), PCr, and adenosine triphosphate (ATP). The time constant tau of PCr recovery (time to achieve 66.3% maximal concentration during recovery) will be used to determine mitochondrial function.
次要结局
- Systolic Blood Pressure(30 minutes before hemodialysis, during dialysis, and up to 1 hour after hemodialysis)
研究者
Jorge Gamboa
Research Associate Professor
Vanderbilt University Medical Center