Study of Nicotinamide Riboside Supplementation in Allogeneic Hematopoietic Cell Transplantation

A Pilot Study of Nicotinamide Riboside Supplementation in Allogeneic Hematopoietic Cell Transplantation

The purpose of this study is to find a safe and tolerable way to improve engraftment after transplant. Research studies have shown that adding nicotinamide riboside to donor cells has the potential to increase blood stem cell numbers and potentially decrease the time to engraftment. Also, nicotinamide riboside, TRU NIAGEN (the study drug) is a type of vitamin B supplement that the general public can get without a prescription and is well tolerated.

Study Overview

• Status: Recruiting
• Conditions: Allogeneic Hematopoietic Cell Transplantation
• Intervention / Treatment: Drug: Nicotinamide riboside (NR)

Detailed Description

This is a single-center, pilot feasibility study of NR supplementation in allogeneic (donor) HCT in which the study team is seeking to obtain preliminary data on any beneficial effect of increasing NAD+ levels in-vivo to facilitate engraftment. Engraftment is defined as the process during which transplanted stem cells begin to grow in the bone marrow and produce new white blood cells, red blood cells, and platelets. It takes about 14 to 24 days for donor cells to engraft after infusion, and the time between which blood counts fall to the time when they recover is a very critical period. Transfusions are frequently required to prevent bleeding and antibiotics are needed to prevent infections during this critical time period. Shortening the time of engraftment decreases these risks and can improve long-term health status.

The primary objectives of this study is to evaluate safety and tolerability of NR supplementation

The secondary objective of this study is to evaluate neutrophil and platelet recovery after HCT

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Ronald Sobecks, MD; Phone Number: 1-866-223-8100; Email: TaussigResearch@ccf.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic, Case Comprehensive Cancer Center
      • Contact: Navneet Majhail, MD; Phone Number: 866-223-8100; Email: TaussigResearch@ccf.org
      • Principal Investigator: Navneet Majhail, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• All disease indications for allogeneic hematopoietic cell transplantation except for myelofibrosis.
• Subject must meet program eligibility criteria* for myeloablative conditioning alloHCT and plan to undergo myeloablative conditioning.
• HLA-identical related donor or unrelated human donor source with bone marrow graft.
• Subjects must provide a written informed consent.

Exclusion Criteria:

• History of allergy or intolerance to NR precursor compounds, including niacin or nicotinamide
• Pregnant or breastfeeding women are excluded from this study since allogeneic HCT is a strict contraindication.
• Subjects with uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nicotinamide riboside (NR)	Drug: Nicotinamide riboside (NR); Nicotinamide riboside, PO, 500mgtwice daily for 21, 28, and 35 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of participants who receive >75% of scheduled doses.	Tolerability of NR in allogeneic HCT recipients, defined as 8 or more of 15 participants (i.e. at least 50% of enrolled subjects) able to receive >75% of their scheduled doses (overall rate 53%, 95% confidence intervals 33%-86%). This will include both patients who discontinue NR due to study drug related toxicity and patients who are not able to stay on NR due to transplant related toxicity that limits ability to take the drug	day +7
Percent of participants who receive >75% of scheduled doses.	Tolerability of NR in allogeneic HCT recipients, defined as 8 or more of 15 participants (i.e. at least 50% of enrolled subjects) able to receive >75% of their scheduled doses (overall rate 53%, 95% confidence intervals 33%-86%). This will include both patients who discontinue NR due to study drug related toxicity and patients who are not able to stay on NR due to transplant related toxicity that limits ability to take the drug	day +14
Percent of participants who receive >75% of scheduled doses.	Tolerability of NR in allogeneic HCT recipients, defined as 8 or more of 15 participants (i.e. at least 50% of enrolled subjects) able to receive >75% of their scheduled doses (overall rate 53%, 95% confidence intervals 33%-86%). This will include both patients who discontinue NR due to study drug related toxicity and patients who are not able to stay on NR due to transplant related toxicity that limits ability to take the drug	day +21
Percent of participants experiencing a CTCAE 5.0 grade 3 or higher related to the study drug	Safety of NR in allogeneic HCT recipients as measured by percent of participants experiencing a CTCAE 5.0 grade 3 or higher that is related to the study drug	day +7
Percent of participants experiencing a CTCAE 5.0 grade 3 or higher related to the study drug	Safety of NR in allogeneic HCT recipients as measured by percent of participants experiencing a CTCAE 5.0 grade 3 or higher that is related to the study drug	day +14
Percent of participants experiencing a CTCAE 5.0 grade 3 or higher related to the study drug	Safety of NR in allogeneic HCT recipients as measured by percent of participants experiencing a CTCAE 5.0 grade 3 or higher that is related to the study drug	day +21

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median days to neutrophil recovery after HCT	Median and range of days to neutrophil recovery after HCT. Recovery defined as first day of three consecutive days with absolute neutrophil count 500 cells/mm3 (0.5 x 109/L) or greater	Up to 100 days from start of treatment
Median days to platelet recovery after HCT	Median and range of days to Platelet recovery after HCT. Recovery defined as first day of three consecutive days with platelet count 20,000/mm3 (20 x 109/L) or greater and unsupported by platelet transfusions.	Up to 100 days from start of treatment

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Investigators: Principal Investigator: Ronald Sobecks, MD, Cleveland Clinic, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2020
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: March 31, 2020
• First Submitted That Met QC Criteria: April 1, 2020
• First Posted (Actual): April 2, 2020

Study Record Updates

• Last Update Posted (Actual): October 11, 2023
• Last Update Submitted That Met QC Criteria: October 10, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Vitamin B Complex; Nicotinic Acids; Niacinamide; Niacin
• Other Study ID Numbers: CASE2Z20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will not be shared publicly

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes