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

NCT07808333 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: IRB26-0972IND Number: 184022
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Keywords

nicotinamide; NAD+; neuroprotection; retinal ganglion cells; GCIPL; optical coherence tomography; OCT-A; glaucoma progression; macular imaging; vitamin B3

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (5)

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

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

• Visual Field Mean Deviation Slope

  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

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

• Nicotinamide Adherence Rate

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

• Study Retention Rate

  Month 12 (52 weeks post-randomization)

Other Outcomes (2)

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

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

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

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

Study Arms (2)

High-Dose Oral Nicotinamide Plus Standard Glaucoma Care

EXPERIMENTAL

Participants receive immediate-release oral nicotinamide titrated from 1.5 g/day (500 mg three times daily with meals, Weeks 1 through 6) to 3.0 g/day (1,500 mg twice daily \[three 500 mg tablets per administration, twice daily\] with meals, Week 7 through Month 12), in addition to individualized standard glaucoma therapy. Dose advancement at Week 7 requires confirmation at the Month 1 remote safety contact that no Grade 2 or higher hepatic adverse event is present and gastrointestinal tolerability is acceptable.

Drug: Nicotinamide; Other: Standard Glaucoma Therapy

Standard Glaucoma Care Alone (Active Control)

ACTIVE COMPARATOR

Participants receive individualized standard glaucoma therapy per the 2026 American Academy of Ophthalmology Primary Open-Angle Glaucoma Preferred Practice Pattern, including intraocular pressure lowering with topical prostaglandin analogs and/or selective laser trabeculoplasty, with monitoring by optical coherence tomography, perimetry, and intraocular pressure measurement at 3 to 6 month intervals. No supplemental nicotinamide is administered.

Other: Standard Glaucoma Therapy

Interventions

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.

Also known as: Niacinamide, Vitamin B3, NAM, Rugby Niacinamide 500 mg

High-Dose Oral Nicotinamide Plus Standard Glaucoma Care

Standard Glaucoma Therapy OTHER

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.

High-Dose Oral Nicotinamide Plus Standard Glaucoma Care; Standard Glaucoma Care Alone (Active Control)

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Confirmed glaucomatous structural damage on SD-OCT (average GCIPL and/or RNFL below age-adjusted normative mean on device-generated classification) and/or a reproducible visual field defect on Humphrey Visual Field 24-2 consistent with glaucoma, as confirmed by the enrolling glaucoma specialist at screening
• Macular GCIPL and peripapillary RNFL above device-specific SD-OCT floor effect in the study eye
• Currently receiving stable intraocular pressure-lowering therapy (topical medications and/or prior selective laser trabeculoplasty) for at least 4 months prior to enrollment, with no planned changes to glaucoma therapy at the time of enrollment
• Intraocular pressure of 21 mmHg or less on current therapy at the screening visit in the study eye
• Established patient receiving ongoing glaucoma care at University of Chicago Medicine Duchossois Center for Advanced Medicine Eye Clinic
• Willing and able to provide written informed consent and comply with all study visit schedules and procedures
• Study eye selection: when POAG is present bilaterally, the study eye is defined as the eye with more severe disease (worse VF MD) that meets all eligibility criteria; if both eyes are equivalent in severity, the right eye is designated by default

You may not qualify if:

• 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
• Renal dysfunction: eGFR less than 30 mL/min/1.73 m2
• Current use of, or unwillingness to abstain from:
• nicotinamide, niacinamide, nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), or any other NAD+-precursor supplement not dispensed by the study; high-dose niacin or vitamin B3; Ginkgo biloba; CoQ10; isoniazid; pyrazinamide; carbamazepine; phenobarbital; primidone; or sustained-release niacin or nicotinamide formulations
• Poorly controlled diabetes mellitus: HbA1c greater than 9.0% at screening
• Normal tension glaucoma with documented intraocular pressure consistently 21 mmHg or less without hypotensive therapy
• Participation in another investigational drug trial within 30 days of screening
• Pregnancy, lactation, or intent to become pregnant during the study period
• Significant cognitive impairment or inability to comply with study requirements
• Clinically significant media opacity (corneal, lenticular, or vitreal) sufficient to degrade OCT signal quality below device-minimum thresholds, even if BCVA of 20/40 or better is preserved
• Active or recent uveitis or intraocular inflammation in the study eye within the past 3 months
• Any condition that, in the investigator's judgment, would preclude safe participation or confound result interpretation

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

University of Chicago Medicine Duchossois Center for Advanced Medicine

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

Glaucoma, Open-Angle

Interventions

Niacinamide

Condition Hierarchy (Ancestors)

Glaucoma; Ocular Hypertension; Eye Diseases

Intervention Hierarchy (Ancestors)

Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Steven C Quan, OD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Steven C Quan, OD

CONTACT

773-702-1611; scquan@bsd.uchicago.edu

Elza Rachid, MD

CONTACT

773-702-1611; Elza.Rachid@bsd.uchicago.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label trial. Participants and investigators are unmasked to treatment assignment. Outcome assessors (central SD-OCT and visual field readers) are masked to treatment assignment via de-identified participant IDs.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants are randomized 1:1 to two parallel arms using computer-generated permuted block randomization stratified by glaucoma severity (mild: VF MD -2 to -6 dB vs. moderate: VF MD -6 to -12 dB) and race/ethnicity. Arm 1 receives high-dose oral nicotinamide plus standard glaucoma care; Arm 2 receives standard glaucoma care alone. All structural and functional outcome assessments are adjudicated by masked central readers using de-identified participant IDs. There is no crossover between arms.

Study Record Dates

• First Submitted: September 2, 2026
• First Posted: September 8, 2026
• Study Start (Estimated): June 1, 2027
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): October 31, 2029
• Last Updated: September 11, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 12 months after primary study results publication
• Access Criteria: Requests submitted to the principal investigator with a brief description of the proposed analysis and intended use. De-identified data shared under a formal data use agreement per University of Chicago institutional policy.

Locations

US (1)