Pharmacokinetics, Pharmacodynamics and Safety of Basis in Acute Kidney Injury Study

Not Applicable

Completed

• Conditions: Acute Kidney Injury
• Interventions: Dietary Supplement: Placebo; Dietary Supplement: Basis

• Registration Number: NCT03176628
• Lead Sponsor: Massachusetts General Hospital

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.

Study Timeline

• Study First Submitted: 2017-05-31
• Study First Submitted QC: 2017-06-02
• Study First Posted: 2017-06-05
• Study Start: 2017-11-01
• Primary Completion: 2018-09-11
• Study Completion: 2018-09-11
• Status Verified: 2019-06
• Last Update Submitted: 2019-06-26
• Last Update Posted: 2019-06-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Capsules identical in appearance and number to the agent used in Steps 1-4.
Basis	Basis	Nicotinamide riboside (NR) and pterostilbene oral capsules 250mg/50mg (Step 1) twice daily for 2 days. If the study progresses to Steps 2, 3, and 4, then 2x, 3x, and 4x the doses in Step 1 will be administered.

Primary Outcome Measures

Name	Time	Method
Area Under the Curve [AUC] of NR	2 days	Area Under the Curve \[AUC\] of NR 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 pterostilbene	2 days	Maximum plasma concentration \[Cmax\] of pterostilbene 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
Maximum plasma concentration [Cmax] of NR	2 days	Maximum plasma concentration \[Cmax\] of NR after oral administration of Basis
Incidence of Treatment-Emergent Laboratory Abnormalities (Safety)	2 days	comprehensive metabolic panel (including liver function tests), complete blood count

Secondary Outcome Measures

Name	Time	Method
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
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

Trial Locations

Locations (1)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States