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

Acute Kidney Injury Clinical Trial

— BAKIS  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03176628
• Other study ID #: 2017P000908
• Status: Completed
• Phase: N/A
• Start date: November 1, 2017
• Est. completion date: September 11, 2018

Study information

• Verified date: June 2019
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: September 11, 2018
• Est. primary completion date: September 11, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Kidney Injury
• Wounds and Injuries

Intervention

Dietary Supplement:
• Basis
NR is a form of vitamin B3; Pterostilbene is a natural dietary compound and the primary antioxidant component of blueberries
• Placebo
Placebo capsule(s)

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	Elysium Health

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum plasma concentration [Cmax] of NR	Maximum plasma concentration [Cmax] of NR after oral administration of Basis	2 days
Primary	Maximum plasma concentration [Cmax] of pterostilbene	Maximum plasma concentration [Cmax] of pterostilbene after oral administration of Basis	2 days
Primary	Area Under the Curve [AUC] of NR	Area Under the Curve [AUC] of NR after oral administration of Basis	2 days
Primary	Area Under the Curve [AUC] of pterostilbene	Area Under the Curve [AUC] of pterostilbene after oral administration of Basis	2 days
Primary	Incidence of Treatment-Emergent Adverse Events (Safety)	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	2 days
Primary	Incidence of Treatment-Emergent Laboratory Abnormalities (Safety)	comprehensive metabolic panel (including liver function tests), complete blood count	2 days
Secondary	NAD+ levels	To determine the increase in NAD+ levels in white blood cells (WBCs) following twice daily Basis administration	2 days
Secondary	Dose finding for 50% increase in NAD+ levels in WBCs	Dose of Basis that leads to 50% increase in NAD+ levels in WBC	2 days
Secondary	Dose finding for 100% increase in NAD+ levels in WBCs	Dose of Basis that leads to 100% increase in NAD+ levels in WBC	2 days