20 Participants Needed

NR Supplementation for Bone Marrow Transplant Engraftment Improvement

RS
Overseen ByRonald Sobecks, MD
Age: 18+
Sex: Any
Trial Phase: Phase < 1
Sponsor: Case Comprehensive Cancer Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Approved in 6 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is Nicotinamide Riboside (NR) safe for human use?

Nicotinamide Riboside (NR) has been studied in humans and is generally recognized as safe, with no significant differences in adverse events compared to a placebo in clinical trials. It has been tested at various doses and shown to be well-tolerated, with no reports of serious side effects.12345

How does the NR supplementation treatment differ from other treatments for bone marrow transplant engraftment improvement?

NR supplementation is unique because it focuses on enhancing the body's natural processes to improve bone marrow transplant outcomes, potentially offering a novel approach compared to traditional methods that often involve drugs or gene therapy to protect or stimulate bone marrow cells.678910

Research Team

Ronald Sobecks, MD | Cleveland Clinic

Ronald Sobecks, MD

Principal Investigator

Cleveland Clinic, Case Comprehensive Cancer Center

Eligibility Criteria

This trial is for individuals who are eligible for a bone marrow transplant with myeloablative conditioning and have an HLA-identical donor. It's not suitable for pregnant or breastfeeding women, those with uncontrolled illnesses or psychiatric conditions that could affect compliance, or anyone allergic to NR compounds like niacin.

Inclusion Criteria

Subjects must provide a written informed consent
I have a matching donor for my bone marrow transplant.
I am eligible and planning to undergo a bone marrow transplant with intensive preparation.
See 1 more

Exclusion Criteria

History of allergy or intolerance to NR precursor compounds, including niacin or nicotinamide
I am not pregnant or breastfeeding.
Subjects with uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nicotinamide riboside supplementation to improve engraftment after allogeneic hematopoietic cell transplantation

Up to 21 days
Frequent monitoring visits during treatment

Engraftment Monitoring

Participants are monitored for engraftment, defined as the process during which transplanted stem cells begin to grow in the bone marrow

14-24 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including neutrophil and platelet recovery

Up to 100 days

Treatment Details

Interventions

  • Nicotinamide Riboside (NR)
Trial OverviewThe study is testing the addition of Nicotinamide Riboside (NR), a vitamin B supplement, to donor cells in bone marrow transplants. The goal is to see if it can safely increase stem cell numbers and speed up engraftment after the transplant.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Nicotinamide riboside (NR)Experimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

Case Comprehensive Cancer Center

Lead Sponsor

Trials
472
Recruited
33,400+

Findings from Research

In an 8-week clinical trial with overweight but healthy participants, nicotinamide riboside (NR) significantly increased whole blood NAD+ levels in a dose-dependent manner, with increases of 22%, 51%, and 142% for doses of 100, 300, and 1000 mg, respectively.
The study found NR to be safe, with no significant adverse effects reported compared to placebo, and it did not negatively impact cholesterol levels or 1-carbon metabolism, supporting its potential as a dietary supplement.
Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults.Conze, D., Brenner, C., Kruger, CL.[2023]
Nicotinamide (NAM), a form of vitamin B-3, enhances the engraftment efficacy of cord blood-derived CD34(+) cells by delaying their differentiation and increasing their ability to migrate to the bone marrow, which is crucial for effective transplantation.
The study suggests that NAM's effects are specifically linked to the inhibition of the SIRT1 enzyme, highlighting its potential clinical utility in improving the expansion and functionality of hematopoietic stem cells for therapeutic use.
Nicotinamide, a SIRT1 inhibitor, inhibits differentiation and facilitates expansion of hematopoietic progenitor cells with enhanced bone marrow homing and engraftment.Peled, T., Shoham, H., Aschengrau, D., et al.[2022]
A single oral dose of nicotinamide riboside (NR) can significantly increase blood NAD+ levels, with a reported rise of up to 2.7-fold in an individual, indicating its potential efficacy as an NAD+ precursor.
In a clinical trial involving various doses (100, 300, and 1,000 mg), NR was shown to produce dose-dependent increases in blood NAD+ metabolites, and the formation of nicotinic acid adenine dinucleotide (NAAD) from NR was identified as a sensitive biomarker for effective NAD+ repletion.
Nicotinamide riboside is uniquely and orally bioavailable in mice and humans.Trammell, SA., Schmidt, MS., Weidemann, BJ., et al.[2021]

References

Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults. [2023]
Nicotinamide, a SIRT1 inhibitor, inhibits differentiation and facilitates expansion of hematopoietic progenitor cells with enhanced bone marrow homing and engraftment. [2022]
Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. [2021]
Safety Assessment of High-Purity, Synthetic Nicotinamide Riboside (NR-E) in a 90-Day Repeated Dose Oral Toxicity Study, With a 28-Day Recovery Arm. [2021]
Nicotinamide Riboside-The Current State of Research and Therapeutic Uses. [2021]
[Hematopoietic stimulation for enhanced bone marrow regeneration after chemotherapy (author's transl)]. [2019]
7.Russia (Federation)pubmed.ncbi.nlm.nih.gov
[The stimulating effect of sialic acid on the processes of postradiation hemopoietic regeneration]. [2013]
Retroviral vectors containing a variant dihydrofolate reductase gene for drug protection and in vivo selection of hematopoietic cells. [2017]
Retroviral transfer of the hENT2 nucleoside transporter cDNA confers broad-spectrum antifolate resistance in murine bone marrow cells. [2021]
10.United Statespubmed.ncbi.nlm.nih.gov
Sensitization of hematopoietic stem and progenitor cells to trimetrexate using nucleoside transport inhibitors. [2021]