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

NCT03176628 | Completed DMC

• 1 other identifier: 2017P000908
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Kidney Injury

Keywords

Pharmacokinetics; Pharmacodynamics

Outcome Measures

Primary Outcomes (6)

• Maximum plasma concentration [Cmax] of NR

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

  2 days

• Maximum plasma concentration [Cmax] of pterostilbene

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

  2 days

• Area Under the Curve [AUC] of NR

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

  2 days

• Area Under the Curve [AUC] of pterostilbene

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

  2 days

• 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

• Incidence of Treatment-Emergent Laboratory Abnormalities (Safety)

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

  2 days

Secondary Outcomes (3)

• NAD+ levels

  2 days

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

  2 days

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

  2 days

Study Arms (2)

Basis

EXPERIMENTAL

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.

Dietary Supplement: Basis

Placebo

PLACEBO COMPARATOR

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

Dietary Supplement: Placebo

Interventions

Basis DIETARY_SUPPLEMENT

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

Also known as: nicotinamide riboside (NR) and pterostilbene

Basis

Placebo DIETARY_SUPPLEMENT

Placebo capsule(s)

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Elysium Health: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02118, United States

Location

Related Publications (1)

• 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.

  PMID: 32791973 DERIVED

MeSH Terms

Conditions

Acute Kidney Injury

Interventions

Radial Basis Function Networks; nicotinamide-beta-riboside; Pterocarpus marsupium

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Neural Networks, Computer; Mathematical Concepts

Study Officials

• Eugene Rhee, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Placebo capsules are identical in appearance to active agent.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

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

Study Record Dates

• First Submitted: May 31, 2017
• First Posted: June 5, 2017
• Study Start: November 1, 2017
• Primary Completion: September 11, 2018
• Study Completion: September 11, 2018
• Last Updated: June 27, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)