Impact of Nicotinamide Riboside (NR) on Kidney Function in Patients Undergoing Cardiac Surgery.A Randomized Controlled Pilot Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Impact of nicotinamide riboside (NR) on kidney function in patients undergoing cardiac surgery.
研究概览
简要总结
Acute kidney injury (AKI) associated with cardiac surgery is the most important complication in adult patients undergoing open heart surgery and is associated with increased mortality and morbidity. In patients in intensive care units, it is the second most common type of AKI after AKI secondary to sepsis. There is currently no specific treatment for AKI. Supportive measures include renal support therapy for patients with severe AKI, and mortality in this subgroup of patients exceeds 50%. Increasing NAD+ with niacinamide has been shown to prevent various etiologies of experimental AKI in mice, and an early pilot study has shown both increased NAD levels following administration of nicotinamide riboside with pterostilbene NPRT and the safety of niacinamide in patients undergoing cardiac surgery.
详细描述
AKI associated with cardiac surgery is a condition with a high incidence of morbidity and mortality, without pharmacological interventions approved for its prevention or treatment. As far as we know, there is no study that evaluates the impact of the administration of nicotinamide riboside on renal function in patients undergoing cardiac surgery.
Implementation of this relatively low-cost intervention and adequate safety profile would reduce in-hospital complications in risk patients undergoing cardiac surgery.
Nicotinamide adenine dinucleotide (NAD+) is a cellular factor related to metabolism and longevity. NAD+ is a required cofactor of SIRT1, a nuclear deacetylase that modulates chromatin structure, gene expression, prolongs lifespan in organisms, and ameliorates age-related diseases. Experimental AKI in mice rapidly leads to reduced NAD+ levels in the kidney resulting from a combination of decreased NAD+ biosynthesis and increased NAD+ consumption. Likewise, mice deficient in SIRT1 are more susceptible to AKI and when there is overexpression of SIRT1 they are protected from AKI. These studies describe the modulation of NAD+ and SIRT1 as a potential therapeutic approach in AKI. Similarly, in subjects with AKI, there is evidence of a 50% reduction in plasma NAD. Increasing NAD+ with niacinamide has been shown to prevent various etiologies of experimental AKI in mice, and an early pilot study has shown both increased NAD levels following administration of nicotinamide riboside with pterostilbene NPRT and the safety of niacinamide in patients undergoing cardiac surgery.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
The protocol contemplates triple blinding for the intervention. The inclusion and follow-up of patients will be carried out by the team of clinical investigators, who will remain blinded to the assigned group. Assignment to intervention groups will be carried out by an investigator independent of the team of clinical investigators and the clinical management team, who will remain blind to the information and follow-up of the patients. The medical team in charge of hospital treatment (surgery, cardiology, intensive care and nephrology), and the patient himself will remain blind to the assigned intervention group.
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
- •Heart valve replacement surgery
- •Sign of informed consent
排除标准
- •Allergy to any of the components
- •Platelet count less than 100,000
- •Weight less than 50Kg or over 100Kg
- •Any type of infectious disease (e. g, Endocarditis)
- •GFR less or equal to 15ml/min/m2 or with renal replacement therapy
- •IV or oral contrast medium 72 hrs prior recruitment
- •LRA 7 days prior to surgery
结局指标
主要结局
Impact of nicotinamide riboside (NR) on kidney function in patients undergoing cardiac surgery.
时间窗: 2 years
The NAD+ and NADH will be measured with the quantitation of the cofactor SIRT1 with a human SIRT1 ELISA kit (novus, NBP2-80300) and a fluorogenic assay SIRT1 CS1040 and flow cytometry.
次要结局
未报告次要终点
研究者
Magdalena Madero
MD. Head of Nephrology
Instituto Nacional de Cardiologia Ignacio Chavez
