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

Primary Purpose

Acute Kidney Injury

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Basis

Placebo

About this trial

This is an interventional other trial for Acute Kidney Injury focused on measuring Pharmacokinetics, Pharmacodynamics

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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:
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.
Able to provide written informed consent in compliance with the Human Investigation Review Committee (IRB).

Exclusion Criteria:

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.

Sites / Locations

Massachusetts General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Basis

Placebo

Arm Description

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.

Capsules identical in appearance and number to the agent used in Steps 1-4.

Outcomes

Primary Outcome Measures

Maximum plasma concentration [Cmax] of NR

Maximum plasma concentration [Cmax] of NR after oral administration of Basis

Maximum plasma concentration [Cmax] of pterostilbene

Maximum plasma concentration [Cmax] of pterostilbene after oral administration of Basis

Area Under the Curve [AUC] of NR

Area Under the Curve [AUC] of NR after oral administration of Basis

Area Under the Curve [AUC] of pterostilbene

Area Under the Curve [AUC] of pterostilbene after oral administration of Basis

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

Incidence of Treatment-Emergent Laboratory Abnormalities (Safety)

comprehensive metabolic panel (including liver function tests), complete blood count

Secondary Outcome Measures

NAD+ levels

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

Dose of Basis that leads to 50% increase in NAD+ levels in WBC

Dose finding for 100% increase in NAD+ levels in WBCs

Dose of Basis that leads to 100% increase in NAD+ levels in WBC

Full Information

NCT ID

NCT03176628

First Posted

May 31, 2017

Last Updated

June 26, 2019

Sponsor

Massachusetts General Hospital

Collaborators

Elysium Health

1. Study Identification

Unique Protocol Identification Number

NCT03176628

Brief Title

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

Acronym

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)

Study Type

Interventional

2. Study Status

Record Verification Date

June 2019

Overall Recruitment Status

Completed

Study Start Date

November 1, 2017 (Actual)

Primary Completion Date

September 11, 2018 (Actual)

Study Completion Date

September 11, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Massachusetts General Hospital

Collaborators

Elysium Health

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Kidney Injury

Keywords

Pharmacokinetics, Pharmacodynamics

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

Randomized 5 subjects in active arm (Basis) : 1 subject in control (placebo)

Masking

ParticipantCare ProviderInvestigator

Masking Description

Placebo capsules are identical in appearance to active agent.

Allocation

Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Basis

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Capsules identical in appearance and number to the agent used in Steps 1-4.

Intervention Type

Dietary Supplement

Intervention Name(s)

Basis

Other Intervention Name(s)

nicotinamide riboside (NR) and pterostilbene

Intervention Description

NR is a form of vitamin B3; Pterostilbene is a natural dietary compound and the primary antioxidant component of blueberries

Intervention Type

Dietary Supplement

Intervention Name(s)

Placebo

Intervention Description

Placebo capsule(s)

Primary Outcome Measure Information:

Title

Maximum plasma concentration [Cmax] of NR

Description

Maximum plasma concentration [Cmax] of NR after oral administration of Basis

Time Frame

2 days

Title

Maximum plasma concentration [Cmax] of pterostilbene

Description

Maximum plasma concentration [Cmax] of pterostilbene after oral administration of Basis

Time Frame

2 days

Title

Area Under the Curve [AUC] of NR

Description

Area Under the Curve [AUC] of NR after oral administration of Basis

Time Frame

2 days

Title

Area Under the Curve [AUC] of pterostilbene

Description

Area Under the Curve [AUC] of pterostilbene after oral administration of Basis

Time Frame

2 days

Title

Incidence of Treatment-Emergent Adverse Events (Safety)

Description

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

Time Frame

2 days

Title

Incidence of Treatment-Emergent Laboratory Abnormalities (Safety)

Description

comprehensive metabolic panel (including liver function tests), complete blood count

Time Frame

2 days

Secondary Outcome Measure Information:

Title

NAD+ levels

Description

To determine the increase in NAD+ levels in white blood cells (WBCs) following twice daily Basis administration

Time Frame

2 days

Title

Dose finding for 50% increase in NAD+ levels in WBCs

Description

Dose of Basis that leads to 50% increase in NAD+ levels in WBC

Time Frame

2 days

Title

Dose finding for 100% increase in NAD+ levels in WBCs

Description

Dose of Basis that leads to 100% increase in NAD+ levels in WBC

Time Frame

2 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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). Exclusion Criteria: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Eugene Rhee, MD

Organizational Affiliation

Massachusetts General Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Massachusetts General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02118

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

32791973

Citation

Simic P, Vela Parada XF, Parikh SM, Dellinger R, Guarente LP, Rhee EP. Nicotinamide riboside with pterostilbene (NRPT) increases NAD+ in patients with acute kidney injury (AKI): a randomized, double-blind, placebo-controlled, stepwise safety study of escalating doses of NRPT in patients with AKI. BMC Nephrol. 2020 Aug 13;21(1):342. doi: 10.1186/s12882-020-02006-1.

Results Reference

derived

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

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