Comparisons of NAD Precursors for Neuroenhancement in Glaucoma Patients

Last updated: June 20, 2025
Sponsor: Christopher Kai Shun Leung
Overall Status: Active - Recruiting

Phase

2

Condition

Glaucoma

Treatment

Nicotinamide Mononucleotide

Placebo (Corn Starch)

Nicotinamide

Clinical Study ID

NCT06991712
H029
  • Ages > 18
  • All Genders

Study Summary

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.

Eligibility Criteria

Inclusion

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 24-2SITA standard

Exclusion

Exclusion Criteria:

  • pathological myopia

  • diseases that may cause visual field loss or optic disc abnormalities other thanglaucoma

  • 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.

Study Design

Total Participants: 138
Treatment Group(s): 5
Primary Treatment: Nicotinamide Mononucleotide
Phase: 2
Study Start date:
May 19, 2025
Estimated Completion Date:
December 31, 2026

Study Description

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.

Connect with a study center

  • HKU Eye Centre

    Wong Chuk Hang,
    Hong Kong

    Active - Recruiting

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