Acute Kidney Injury
Conditions
Keywords
Pharmacokinetics, Pharmacodynamics
Brief summary
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.
Detailed description
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.
Interventions
DIETARY_SUPPLEMENTBasis
NR is a form of vitamin B3; Pterostilbene is a natural dietary compound and the primary antioxidant component of blueberries
DIETARY_SUPPLEMENTPlacebo
Placebo capsule(s)
Sponsors
Elysium Health
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Placebo capsules are identical in appearance to active agent.
Intervention model description
Randomized 5 subjects in active arm (Basis) : 1 subject in control (placebo)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female hospitalized patients, age ≥ 18 years. 2. 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). 3. Adequate hematological and liver function, as assessed by the following laboratory requirements: 1. Hemoglobin ≥10.0 g/dL 2. Absolute neutrophil count (ANC) ≥1,500/mm3 3. Platelet count 100,000/mm3 4. Total bilirubin ≤1.5 x upper limit of normal (ULN). 5. ALT and AST ≤2.5 x ULN. 4. Able to provide written informed consent in compliance with the Human Investigation Review Committee (IRB).
Exclusion criteria
1. Exposure to any investigational agent within 30 days prior to enrollment. 2. Known allergy to any of the study drugs or their excipients. 3. Currently pregnant (confirmed with a positive serum pregnancy test) or nursing. 4. 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. 5. 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 6. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Laboratory Abnormalities (Safety) | 2 days | comprehensive metabolic panel (including liver function tests), complete blood count |
| Area Under the Curve [AUC] of NR | 2 days | Area Under the Curve \[AUC\] of NR after oral administration of Basis |
| Area Under the Curve [AUC] of pterostilbene | 2 days | Area Under the Curve \[AUC\] of pterostilbene after oral administration of Basis |
| Incidence of Treatment-Emergent Adverse Events (Safety) | 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 NR | 2 days | Maximum plasma concentration \[Cmax\] of NR after oral administration of Basis |
| Maximum plasma concentration [Cmax] of pterostilbene | 2 days | Maximum plasma concentration \[Cmax\] of pterostilbene after oral administration of Basis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose finding for 50% increase in NAD+ levels in WBCs | 2 days | Dose of Basis that leads to 50% increase in NAD+ levels in WBC |
| Dose finding for 100% increase in NAD+ levels in WBCs | 2 days | Dose of Basis that leads to 100% increase in NAD+ levels in WBC |
| NAD+ levels | 2 days | To determine the increase in NAD+ levels in white blood cells (WBCs) following twice daily Basis administration |
Countries
United States
Outcome results
None listed