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

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ClinicalTrials.gov Identifier: NCT03176628
Recruitment Status : Completed
First Posted : June 5, 2017
Last Update Posted : June 27, 2019
Sponsor:
Collaborator:
Elysium Health
Information provided by (Responsible Party):
Eugene Rhee, Massachusetts General Hospital

Tracking Information
First Submitted Date  ICMJE May 31, 2017
First Posted Date  ICMJE June 5, 2017
Last Update Posted Date June 27, 2019
Actual Study Start Date  ICMJE November 1, 2017
Actual Primary Completion Date September 11, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 2, 2017)
  • Maximum plasma concentration [Cmax] of NR [ Time Frame: 2 days ]
    Maximum plasma concentration [Cmax] of NR after oral administration of Basis
  • Maximum plasma concentration [Cmax] of pterostilbene [ Time Frame: 2 days ]
    Maximum plasma concentration [Cmax] of pterostilbene after oral administration of Basis
  • Area Under the Curve [AUC] of NR [ Time Frame: 2 days ]
    Area Under the Curve [AUC] of NR after oral administration of Basis
  • Area Under the Curve [AUC] of pterostilbene [ Time Frame: 2 days ]
    Area Under the Curve [AUC] of pterostilbene after oral administration of Basis
  • 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
  • Incidence of Treatment-Emergent Laboratory Abnormalities (Safety) [ Time Frame: 2 days ]
    comprehensive metabolic panel (including liver function tests), complete blood count
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03176628 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 2, 2017)
  • NAD+ levels [ Time Frame: 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 [ Time Frame: 2 days ]
    Dose of Basis that leads to 50% increase in NAD+ levels in WBC
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacokinetics, Pharmacodynamics and Safety of Basis in Acute Kidney Injury Study
Official Title  ICMJE 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)
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 Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE 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
Condition  ICMJE Acute Kidney Injury
Intervention  ICMJE
  • 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
  • Dietary Supplement: Placebo
    Placebo capsule(s)
Study Arms  ICMJE
  • 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.
    Intervention: Dietary Supplement: Basis
  • Placebo Comparator: Placebo
    Capsules identical in appearance and number to the agent used in Steps 1-4.
    Intervention: Dietary Supplement: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 2, 2017)
24
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE September 11, 2018
Actual Primary Completion Date September 11, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03176628
Other Study ID Numbers  ICMJE 2017P000908
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Eugene Rhee, Massachusetts General Hospital
Study Sponsor  ICMJE Massachusetts General Hospital
Collaborators  ICMJE Elysium Health
Investigators  ICMJE
Principal Investigator: Eugene Rhee, MD Massachusetts General Hospital
PRS Account Massachusetts General Hospital
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP