Niacin Modulates Immune Responses in a Phase I Dose-Escalation Clinical Trial of Newly Diagnosed Glioblastoma.

2026-03
Neurology(R) neuroimmunology & neuroinflammation 13(2)
- Candice C Poon
- Kathleen M Hagen
- Susobhan Sarkar
- Reza Mirzaei
- Claudia Silva
- Aito Ueno
- Paula de Robles
- Gloria Roldan-Urgoiti
- V Wee Yong

PubMed: 41632924
DOI: 10.1212/nxi.0000000000200530

Study Design

Type: Clinical Trial
Population: patients with newly diagnosed glioblastoma
Methods: first-in-human phase I clinical trial, niacin administration alongside standard-of-care surgery and chemoradiation
Blinding: Open-label

Background and objectives

Glioblastoma, a highly aggressive and uniformly lethal brain tumor, resists current treatments and immunotherapies by creating a potently immunosuppressive microenvironment. The objective of this study was to determine whether niacin modulates systemic immunity in patients with newly diagnosed glioblastoma.

Methods

In a first-in-human phase I clinical trial (NCT04677049), we investigated the immunologic effects of niacin administration alongside standard-of-care surgery and chemoradiation in patients with newly diagnosed glioblastoma.

Results

Niacin treatment increases the frequencies of circulating memory T cells and natural killer cells while decreasing nonclassical monocytes. Furthermore, niacin elevated serum levels of the proinflammatory cytokine interleukin (IL)-12p70 and granulocyte colony-stimulating factor and reduced growth-regulated α protein.

Discussion

These data demonstrate that niacin induces systemic immunomodulatory effects in patients with glioblastoma, shifting the immune landscape toward an antitumor profile and supporting further evaluation of niacin as a potential therapeutic adjunct.

Trial registration information

This ongoing study was registered as NCT04677049 on March 1, 2021, with the first patient enrolled on March 18, 2021.

Classification of evidence

This study provides Class IV evidence that niacin dose escalation modulates immune response in patients with glioblastoma treated with standard of care, including maximal safe resection, concurrent radiation and temozolomide, and adjuvant temozolomide administration. This is a Class IV study because it is an open-label trial with no blinding or comparison group.

Research Insights

Vitamin B3→Increased IL-12 Levels
Furthermore, niacin elevated serum levels of the proinflammatory cytokine interleukin (IL)-12p70 and granulocyte colony-stimulating factor and reduced growth-regulated α protein.
Effect
Beneficial
Effect size
Moderate
Dose
dose escalation
Vitamin B3→Increased Immune Factor Levels
Furthermore, niacin elevated serum levels of the proinflammatory cytokine interleukin (IL)-12p70 and granulocyte colony-stimulating factor and reduced growth-regulated α protein.
Effect
Beneficial
Effect size
Moderate
Dose
dose escalation
Vitamin B3→Increased Memory T Cell Frequency
Niacin treatment increases the frequencies of circulating memory T cells and natural killer cells while decreasing nonclassical monocytes.
Effect
Beneficial
Effect size
Moderate
Dose
dose escalation
Vitamin B3→Increased Natural Killer Cell Frequency
Niacin treatment increases the frequencies of circulating memory T cells and natural killer cells while decreasing nonclassical monocytes.
Effect
Beneficial
Effect size
Moderate
Dose
dose escalation
Vitamin B3→Reduced Growth-Regulated Alpha Protein Level
Furthermore, niacin elevated serum levels of the proinflammatory cytokine interleukin (IL)-12p70 and granulocyte colony-stimulating factor and reduced growth-regulated α protein.
Effect
Beneficial
Effect size
Moderate
Dose
dose escalation
Vitamin B3→Reduced Nonclassical Monocyte Frequency
Niacin treatment increases the frequencies of circulating memory T cells and natural killer cells while decreasing nonclassical monocytes.
Effect
Beneficial
Effect size
Moderate
Dose
dose escalation