Randomized, Double-blind, Placebo-controlled, Stepwise Study of the Pharmacokinetics, Pharmacodynamics & Safety of Escalating Doses of Basis (Nicotinamide Riboside and Pterostilbene) in Patients With Acute Kidney Injury (AKI)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Area Under the Curve [AUC] of NR
研究概览
简要总结
This study will determine the pharmacokinetics, pharmacodynamics and safety of escalating doses of Basis following twice daily oral administration in patients with acute kidney injury (AKI). Basis is a commercially available nutritional supplement consisting of nicotinamide riboside (NR) and pterostilbene that acts to increase sirtuin activity.
详细描述
Acute kidney injury (AKI) is common, growing in incidence, and associated with significant morbidity and mortality. Sirtuins are anti-aging enzymes that play a diverse role in cellular energy metabolism and gene regulation. Mice deficient in SIRT1 are more susceptible to developing AKI and sirtuin activation is a potential treatment for AKI.
This is a randomized, double-blind, placebo-controlled, stepwise study of escalating doses of Basis (NR/pterostilbene) in patients with AKI. The study will potentially comprise up to four Steps. The purpose of the stepwise approach is to identify the dose of Basis that achieves at least a 50% and up to 100% increase in white blood cell (WBC) content of nicotinamide adenine dinucleotide (NAD+) without side-effects.
During each Step, Basis (5 patients) or placebo (1 patient) will be given twice a day for 2 days. Patients will have frequent blood sampling performed for a 24 hour period following dosing on Day 1 and then at 48 hr. The measurements in blood will include NR/pterostilbene blood concentrations and NAD+ and NAAD (nicotinic acid adenine dinucleotide) concentrations in WBCs.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Placebo capsules are identical in appearance to active agent.
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
- •Male or female hospitalized patients, age ≥ 18 years.
- •Patients who have developed AKI (defined by an increase in serum creatinine by ≥0.3 mg/dL within 48 hours; or an increase in serum creatinine to ≥1.5 times baseline, which is known or presumed to have occurred within the prior seven days).
- •Adequate hematological and liver function, as assessed by the following laboratory requirements:
- •Hemoglobin ≥10.0 g/dL
- •Absolute neutrophil count (ANC) ≥1,500/mm3
- •Platelet count 100,000/mm3
- •Total bilirubin ≤1.5 x upper limit of normal (ULN).
- •ALT and AST ≤2.5 x ULN.
- •Able to provide written informed consent in compliance with the Human Investigation Review Committee (IRB).
排除标准
- •Exposure to any investigational agent within 30 days prior to enrollment.
- •Known allergy to any of the study drugs or their excipients.
- •Currently pregnant (confirmed with a positive serum pregnancy test) or nursing.
- •Unstable or clinically significant concurrent medical condition, psychiatric illness or social situation that would, in the opinion of the investigator, jeopardize the safety of a subject and/or their compliance with the protocol.
- •Baseline CKD stage 4-5 (eGFR<30 mL/minute/1.73 m2 as determined using the Modification of Diet in Renal Disease (MDRD) equation; in cases where the MDRD equation may not be suitable, a 24 hour urine creatinine clearance test may be substituted), prior to current hospitalization
- •Any malignancy with the exception of cervical carcinoma in situ,nonmelanoma skin cancer, or superficial bladder tumors that have been successfully and curatively treated with no evidence of recurrent or residual disease.
结局指标
主要结局
Area Under the Curve [AUC] of NR
时间窗: 2 days
Area Under the Curve \[AUC\] of NR after oral administration of Basis
Incidence of Treatment-Emergent Adverse Events (Safety)
时间窗: 2 days
Subjects will be interviewed to determine onset of nausea, abdominal pain, vomiting, diarrhea, or rash. Adverse events will be characterized as probably related, probably not related, or unknown
Maximum plasma concentration [Cmax] of pterostilbene
时间窗: 2 days
Maximum plasma concentration \[Cmax\] of pterostilbene after oral administration of Basis
Area Under the Curve [AUC] of pterostilbene
时间窗: 2 days
Area Under the Curve \[AUC\] of pterostilbene after oral administration of Basis
Maximum plasma concentration [Cmax] of NR
时间窗: 2 days
Maximum plasma concentration \[Cmax\] of NR after oral administration of Basis
Incidence of Treatment-Emergent Laboratory Abnormalities (Safety)
时间窗: 2 days
comprehensive metabolic panel (including liver function tests), complete blood count
次要结局
- Dose finding for 100% increase in NAD+ levels in WBCs(2 days)
- NAD+ levels(2 days)
- Dose finding for 50% increase in NAD+ levels in WBCs(2 days)
研究者
Eugene Rhee
Assistant Professor of Medicine
Massachusetts General Hospital