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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03176628
Recruitment Status : Completed
First Posted : June 5, 2017
Last Update Posted : June 27, 2019
Elysium Health
Information provided by (Responsible Party):
Eugene Rhee, 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.

Condition or disease Intervention/treatment Phase
Acute Kidney Injury Dietary Supplement: Basis Dietary Supplement: Placebo Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized 5 subjects in active arm (Basis) : 1 subject in control (placebo)
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Placebo capsules are identical in appearance to active agent.
Primary Purpose: Other
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)
Actual Study Start Date : November 1, 2017
Actual Primary Completion Date : September 11, 2018
Actual Study Completion Date : September 11, 2018

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: 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.
Dietary Supplement: Basis
NR is a form of vitamin B3; Pterostilbene is a natural dietary compound and the primary antioxidant component of blueberries
Other Name: nicotinamide riboside (NR) and pterostilbene

Placebo Comparator: Placebo
Capsules identical in appearance and number to the agent used in Steps 1-4.
Dietary Supplement: Placebo
Placebo capsule(s)

Primary Outcome Measures :
  1. Maximum plasma concentration [Cmax] of NR [ Time Frame: 2 days ]
    Maximum plasma concentration [Cmax] of NR after oral administration of Basis

  2. Maximum plasma concentration [Cmax] of pterostilbene [ Time Frame: 2 days ]
    Maximum plasma concentration [Cmax] of pterostilbene after oral administration of Basis

  3. Area Under the Curve [AUC] of NR [ Time Frame: 2 days ]
    Area Under the Curve [AUC] of NR after oral administration of Basis

  4. Area Under the Curve [AUC] of pterostilbene [ Time Frame: 2 days ]
    Area Under the Curve [AUC] of pterostilbene after oral administration of Basis

  5. Incidence of Treatment-Emergent Adverse Events (Safety) [ Time Frame: 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

  6. Incidence of Treatment-Emergent Laboratory Abnormalities (Safety) [ Time Frame: 2 days ]
    comprehensive metabolic panel (including liver function tests), complete blood count

Secondary Outcome Measures :
  1. NAD+ levels [ Time Frame: 2 days ]
    To determine the increase in NAD+ levels in white blood cells (WBCs) following twice daily Basis administration

  2. Dose finding for 50% increase in NAD+ levels in WBCs [ Time Frame: 2 days ]
    Dose of Basis that leads to 50% increase in NAD+ levels in WBC

  3. Dose finding for 100% increase in NAD+ levels in WBCs [ Time Frame: 2 days ]
    Dose of Basis that leads to 100% increase in NAD+ levels in WBC

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03176628

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United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02118
Sponsors and Collaborators
Massachusetts General Hospital
Elysium Health
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Principal Investigator: Eugene Rhee, MD Massachusetts General Hospital
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Eugene Rhee, Assistant Professor of Medicine, Massachusetts General Hospital Identifier: NCT03176628    
Other Study ID Numbers: 2017P000908
First Posted: June 5, 2017    Key Record Dates
Last Update Posted: June 27, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eugene Rhee, Massachusetts General Hospital:
Additional relevant MeSH terms:
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Acute Kidney Injury
Wounds and Injuries
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Vitamin B Complex
Growth Substances
Physiological Effects of Drugs