Comparisons of NAD Precursors for Neuroenhancement in Glaucoma Patients

Comparisons of Nicotinamide Adenine Dinucleotide (NAD) Precursors for Neuroenhancement in Glaucoma Patients

The goal of this clinical trial is to determine whether oral supplementation with different nicotinamide adenine dinucleotide (NAD) precursors can improve visual function in adults with primary open-angle glaucoma. The main questions it aims to answer are:

1. Does daily oral administration of equimolar doses of nicotinamide riboside (NR), nicotinamide (NAM), nicotinamide mononucleotide (NMN), or nicotinic acid (NA) improve visual field sensitivity in glaucoma patients over the short term?
2. How do plasma NAD+ metabolite profiles change after administration of each precursor, and do these changes relate to improvements in visual function?

Researchers will compare NR, NAM, NMN, NA, and placebo groups to see if any of the NAD precursors lead to greater improvements in visual field sensitivity or changes in blood NAD+ metabolite levels compared to placebo.

Participants will:

Be randomly assigned to receive one of the four NAD precursors or placebo daily for two weeks.

Undergo comprehensive eye examinations, including visual field testing and optical coherence tomography, at baseline and after two weeks.

Provide blood samples before and after the intervention for measurement of NAD+ metabolites.

Have safety monitored through clinical examination.

This study will help identify whether boosting NAD+ levels with specific precursors offers functional benefit in glaucoma, and which blood metabolites may mediate these effects.

This prospective randomized, double-blind, placebo-controlled clinical trial evaluates four nicotinamide adenine dinucleotide (NAD) precursors for neuroenhancement in 138 adults with primary open-angle glaucoma. Participants are randomly assigned to receive daily oral supplementation for one week with equimolar doses of nicotinamide riboside (300 mg), nicotinamide (125 mg), nicotinamide mononucleotide (350 mg), nicotinic acid (125 mg), or placebo. The study assesses short-term changes in visual field sensitivity using Humphrey Field Analyzer 24-2 testing and measures NAD+ metabolite profiles through liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis of plasma and peripheral blood mononuclear cells collected at baseline, pre-dose, and post-dose timepoints.

Secondary objectives include comparing pattern electroretinogram nerve fiber layer thickness measurements before and after treatment and analyzing correlations between systemic NAD+ metabolite elevations and functional visual improvements. Blood samples undergo standardized processing with Lymphoprep separation, snap-freezing, and derivatization protocols prior to mass spectrometry analysis using Agilent and Thermo Fisher systems with predefined NAD+ metabolite inclusion lists.

Statistical analysis employs linear mixed models to compare within-group and between-group changes, with intention-to-treat principles. The study design addresses gaps in comparative NAD precursor bioavailability data by testing equimolar doses in a targeted glaucoma population, while maintaining double-blinding through computer-generated randomization and masked outcome assessment.

Inclusion Criteria:

• glaucoma patients
• age ≥ 18 years
• best corrected VA ≥20/40
• IOP <21 mmHg
• visual field mean deviation better than -24 dB on standard automated perimetry 24-2 SITA standard

Exclusion Criteria:

• pathological myopia
• diseases that may cause visual field loss or optic disc abnormalities other than glaucoma
• inability to perform reliable visual field
• suboptimal quality of OCT images
• diabetic retinopathy/maculopathy
• history of abnormal liver function within 12 months
• known allergy to NAD precursor supplement(s)
• pregnancy or lactation
• use of NAD precursor supplements 14 days prior to baseline.