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Trial record 9 of 14 for:    nicotinamide riboside

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

This study is not yet open for participant recruitment.
Verified August 2017 by Eugene Rhee, Massachusetts General Hospital
Sponsor:
ClinicalTrials.gov Identifier:
NCT03176628
First Posted: June 5, 2017
Last Update Posted: September 1, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Elysium Health
Information provided by (Responsible Party):
Eugene Rhee, Massachusetts General Hospital
  Purpose
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 Intervention
Acute Kidney Injury Dietary Supplement: Basis Dietary Supplement: Placebo

Study Type: Interventional
Study Design: 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)

Resource links provided by NLM:


Further study details as provided by Eugene Rhee, Massachusetts General Hospital:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 24
Anticipated Study Start Date: September 2017
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

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.

  Eligibility

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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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 ClinicalTrials.gov identifier (NCT number): NCT03176628


Contacts
Contact: Petra Simic, MD, PhD 617-724-6700 psimic@bwh.harvard.edu
Contact: Katherine E Brock, BS 617-643-9463 kbrock2@mgh.harvard.edu

Locations
United States, Massachusetts
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02118
Contact: Petra Simic, MD, PhD    617-724-6700    psimic@bwh.harvard.edu   
Contact: Katherine E Brock, BS    617-643-9463    kbrock2@mgh.harvard.edu   
Principal Investigator: Eugene Rhee, MD         
Sub-Investigator: Ravi I Thadhani, MD, MPH         
Sub-Investigator: Petra Simic, MD, PhD         
Sponsors and Collaborators
Massachusetts General Hospital
Elysium Health
Investigators
Principal Investigator: Eugene Rhee, MD Massachusetts General Hospital
  More Information

Responsible Party: Eugene Rhee, Assistant Professor of Medicine, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT03176628     History of Changes
Other Study ID Numbers: 2017P000908
First Submitted: May 31, 2017
First Posted: June 5, 2017
Last Update Posted: September 1, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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:
Pharmacokinetics
Pharmacodynamics

Additional relevant MeSH terms:
Wounds and Injuries
Acute Kidney Injury
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Niacinamide
Niacin
Nicotinic Acids
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Vasodilator Agents