Nicotinamide and Pyruvate in Open-Angle Glaucoma: A Randomized Controlled Trial on Neuroprotection-Design and Methodology.

PURPOSE

The Nicotinamide and Pyruvate in Open-Angle Glaucoma Trial aims to establish whether nicotinamide and pyruvate dietary supplementation provides neuroprotection in eyes with treated open-angle glaucoma (OAG).

DESIGN

A prospective, two-site, 21-month, placebo-controlled, double-masked, phase III randomized clinical trial.

PARTICIPANTS

Open-angle glaucoma patients recruited at Columbia University Irving Medical Center and Stanford University between March 1, 2023, and August 30, 2025.

INTERVENTION

Study participants were randomized in a 1:1 ratio to either active product (3 g/day of nicotinamide and 1 g/day of calcium pyruvate) or placebo. Standard-of-care intraocular pressure-lowering treatment is continued throughout the study and can be modified at the discretion of the treating physician.

MAIN OUTCOME MEASURES

The primary outcome measure is a composite of functional change based on automated perimetry of the central 10° of the visual field and/or structural change based on spectral-domain OCT. Periodic blood collection allows for evaluation of intervention-related metabolomics, transcriptomics, and proteomics, and measurement of serum levels of nicotinamide and pyruvate. Secondary outcomes include the evaluation of the tolerability and safety of nicotinamide and pyruvate in OAG and the identification of factors that predispose to greater responsiveness to metabolic neuroprotective therapies in OAG. An intention-to-treat analysis will be performed at the conclusion of the trial.

CONCLUSIONS

This novel trial design may deliver valuable data on the neuroprotective potential of nicotinamide and pyruvate supplementation in glaucoma and improve our understanding of optimal study design for longitudinal randomized clinical trials focused on glaucoma neuroprotection. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.