Nicotinamide for Retinal Protection in Primary Open-Angle Glaucoma (NADIR Trial)

ConditionsGlaucoma, Open-angle Primary Open Angle Glaucoma (POAG)

Trial statusNot yet recruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age40-80

SponsorUniversity of Chicago

About this trial

The goal of this clinical trial is to learn whether a high-dose vitamin B3 supplement called nicotinamide can protect retinal nerve cells in adults with primary open-angle glaucoma (POAG) who are already receiving standard glaucoma eye drops or laser treatment. The main question it aims to answer is: Does adding nicotinamide to standard glaucoma therapy slow the rate of thinning of the inner retinal nerve cell layer (measured by a non-invasive eye scan) compared to standard therapy alone over 12 months?

Participants will be randomly assigned to one of two groups. Participants in the treatment group will take nicotinamide tablets by mouth, starting at a lower dose (1.5 grams per day) for the first 6 weeks and increasing to the full dose (3.0 grams per day) for the remainder of the 12-month study. Participants in the control group will continue their standard glaucoma care without the supplement.

Researchers will compare retinal imaging measurements between the two groups to see whether nicotinamide reduces the rate of retinal nerve cell thinning over time.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age 40 to 80 years, inclusive

Diagnosis of primary open-angle glaucoma (POAG) in at least one eye, confirmed by a licensed ophthalmologist or optometrist based on characteristic optic nerve head changes and/or visual field defects with an open anterior chamber angle

Mild to moderate glaucoma severity in the study eye: Humphrey Visual Field 24-2 mean deviation (MD) between -2.0 and -12.0 dB on at least one reliable test (fixation losses 33% or less, false positive rate 15% or less)

Best-corrected visual acuity (BCVA) of 20/40 or better (Snellen equivalent) in the study eye

Disqualifiers

Advanced glaucoma: visual field MD worse than -12.0 dB in the study eye

Significant retinal disease affecting macular structure or visual field, including advanced age-related macular degeneration, diabetic retinopathy greater than mild non-proliferative, clinically significant diabetic macular edema, major retinal vein occlusion, or non-glaucomatous optic neuropathy

Ocular surgery other than uncomplicated cataract extraction or selective laser trabeculoplasty within the past 6 months

Hepatic dysfunction at baseline: AST or ALT greater than 2 times the upper limit of normal, or total bilirubin greater than 1.5 times the upper limit of normal

Trial design

Design model

Parallel

Treatments tested in this trial

Nicotinamide
Drug
Immediate-release nicotinamide 500 mg tablets (NDC 0-80681-01900; Rugby Laboratories / Contract Pharmacal Corp, Hauppauge NY). Titration phase: 500 mg three times daily (1.5 g/day total) for 6 weeks. Maintenance phase: 1,500 mg twice daily (three 500 mg tablets per administration, twice daily; 3.0 g/day total) from Week 7 through Month 12. Administered orally with meals. Dispensed and tracked by the University of Chicago Institutional Drug Service (IDS) Pharmacy under IND 184022.
Standard Glaucoma Therapy
Other intervention
Individualized intraocular pressure-lowering therapy per the 2026 American Academy of Ophthalmology Primary Open-Angle Glaucoma Preferred Practice Pattern. Includes topical prostaglandin analog eye drops and/or selective laser trabeculoplasty, with clinical monitoring by optical coherence tomography, standard automated perimetry, and intraocular pressure measurement at 3 to 6 month intervals based on disease status.

Treatment groups

96 Participants

are divided into 2 treatment groups

Group A: High-Dose Oral Nicotinamide Plus Standard Glaucoma CareExperimental treatment 2 interventions

Group B: Standard Glaucoma Care Alone (Active Control)Active comparator 1 intervention

Trial outcomes

Primary outcomes

Annualized Rate of Macular Ganglion Cell-Inner Plexiform Layer (GCIPL) Thinning

Rate of change in macular GCIPL thickness (micrometers per year) measured by spectral-domain optical coherence tomography (SD-OCT; Heidelberg Spectralis, minimum Q-score 20) with masked central image reading using de-identified participant IDs. The annualized thinning rate is estimated from repeated measurements using a linear mixed-effects model with random intercepts per participant and an arm-by-time interaction term as the primary inferential parameter.

Time frame

Baseline (Month 0), Month 3, Month 6, and Month 12 (four repeated assessments over 12 months)

Secondary outcomes

Annualized Rate of Peripapillary Retinal Nerve Fiber Layer (RNFL) Thinning

Rate of change in average peripapillary RNFL thickness (micrometers per year) measured by SD-OCT (Heidelberg Spectralis) with masked central reading. Analyzed using the same linear mixed-effects model framework as the primary endpoint. Both average and quadrant-specific RNFL (superior, inferior, temporal, nasal) will be reported.

Time frame

Baseline (Month 0), Month 3, Month 6, and Month 12 (four repeated assessments over 12 months)

Visual Field Mean Deviation Slope

Rate of change in Humphrey Visual Field Analyzer 24-2 SITA Standard mean deviation (decibels per year), estimated as a continuous slope over 12 months using a linear mixed-effects model with random intercepts per participant. Assessed at four timepoints: Baseline, Month 3, Month 6, and Month 12.

Time frame

Baseline through Month 12, assessed at Baseline (Month 0), Month 3, Month 6, and Month 12

Incidence of Grade 2 or Higher Hepatic and Gastrointestinal Adverse Events

Proportion of participants experiencing at least one hepatic adverse event (alanine aminotransferase or aspartate aminotransferase elevation, total bilirubin elevation) or gastrointestinal adverse event graded at Grade 2 or higher per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v6.0). Hepatic laboratory values assessed by comprehensive metabolic panel (CMP) at every study visit and at the Month 1 remote safety contact for all participants in both arms.

Time frame

From randomization through 30 days after the Month 12 visit (approximately 13 months)

Nicotinamide Adherence Rate

Proportion of prescribed nicotinamide doses taken during the maintenance phase (Weeks 7 through 52), assessed by pill count and participant medication diary review at each in-person study visit. Applies to Arm 1 participants only.

Time frame

Maintenance phase: Week 7 (Month 1 remote contact) through Month 12

Other outcomes

Change in Macular Superficial Capillary Plexus Perfusion Density on OCT-A

Change from baseline in macular superficial capillary plexus perfusion density (percent) measured by optical coherence tomography angiography (OCT-A; Optovue Solix FullRange AngioVue, FDA 510(k) K222166; minimum signal strength index 30). Analyzed by ANCOVA with baseline perfusion density as covariate. Designated an exploratory endpoint in this Phase 2a trial; not a pre-specified confirmatory secondary outcome.

Time frame

Baseline (Month 0) and Month 12 (pre- and post-intervention comparison)

Change in Peripapillary Radial Capillary Plexus Perfusion Density on OCT-A

Change from baseline in peripapillary radial capillary plexus (RPC) perfusion density (percent) measured by optical coherence tomography angiography (OCT-A; Optovue Solix FullRange AngioVue, FDA 510(k) K222166; minimum signal strength index 30). Analyzed by ANCOVA with baseline peripapillary perfusion density as covariate and treatment arm as fixed factor. Macular and peripapillary perfusion density metrics are analyzed and reported separately. Designated an exploratory endpoint in this Phase 2a trial.

Time frame

Baseline (Month 0) and Month 12 (pre- and post-intervention comparison)

Sponsors and contacts

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University of Chicago

Lead sponsor

Source ClinicalTrials.gov

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