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

9 septembre 2026 mis à jour par: University of Chicago

NADIR Trial: A Principal Investigator-Initiated, Single-Center, Open-Label, Active-Controlled Phase 2a Study of High-Dose Nicotinamide (Vitamin B3) Supplementation in Adults With Mild to Moderate Primary Open-Angle Glaucoma (POAG)

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.

Aperçu de l'étude

Statut

Pas encore de recrutement

Les conditions

Intervention / Traitement

Description détaillée

Glaucoma causes progressive and irreversible loss of retinal ganglion cells (RGCs), often continuing despite adequate intraocular pressure control. Mitochondrial dysfunction and depletion of NAD+ (nicotinamide adenine dinucleotide) are increasingly recognized as central contributors to RGC vulnerability. Nicotinamide (NAM), a commercially available form of vitamin B3 and potent NAD+ precursor, has demonstrated robust neuroprotection in preclinical glaucoma models and early clinical trials outside the United States.

NADIR is the first IND-regulated, prospective, randomized Phase 2a trial in the United States to evaluate high-dose oral nicotinamide as adjunctive neuroprotective therapy in adults with mild to moderate POAG, using macular ganglion cell layer imaging (SD-OCT) as the primary structural biomarker detectable within 12 months. Ocular vascular perfusion imaging (OCT-A) is included as an exploratory endpoint.

Type d'étude

Interventionnel

Inscription (Estimé)

96

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Sauvegarde des contacts de l'étude

Lieux d'étude

  • États-Unis
    • Illinois
      • Chicago, Illinois, États-Unis, 60637
        • University of Chicago Medicine Duchossois Center for Advanced Medicine
        • Contact:
        • Contact:

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

  • Adulte
  • Adulte plus âgé

Accepte les volontaires sains

Non

La description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: High-Dose Oral Nicotinamide Plus Standard Glaucoma Care
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.
Médicament: Nicotinamide
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.
Autres noms:
  • Vitamine B3
  • Niacinamide
  • NAM
  • Rugby Niacinamide 500 mg
Autre: Standard Glaucoma Therapy
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.
Comparateur actif: Standard Glaucoma Care Alone (Active Control)
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.
Autre: Standard Glaucoma Therapy
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.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Annualized Rate of Macular Ganglion Cell-Inner Plexiform Layer (GCIPL) Thinning
Délai: Baseline (Month 0), Month 3, Month 6, and Month 12 (four repeated assessments over 12 months)
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)

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Annualized Rate of Peripapillary Retinal Nerve Fiber Layer (RNFL) Thinning
Délai: Baseline (Month 0), Month 3, Month 6, and Month 12 (four repeated assessments over 12 months)
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.
Baseline (Month 0), Month 3, Month 6, and Month 12 (four repeated assessments over 12 months)
Visual Field Mean Deviation Slope
Délai: Baseline through Month 12, assessed at Baseline (Month 0), Month 3, Month 6, and Month 12
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.
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
Délai: From randomization through 30 days after the Month 12 visit (approximately 13 months)
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.
From randomization through 30 days after the Month 12 visit (approximately 13 months)
Nicotinamide Adherence Rate
Délai: Maintenance phase: Week 7 (Month 1 remote contact) through Month 12
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.
Maintenance phase: Week 7 (Month 1 remote contact) through Month 12
Study Retention Rate
Délai: Month 12 (52 weeks post-randomization)
Proportion of randomized participants completing the Month 12 study visit with at least one valid post-baseline macular GCIPL measurement. Assessed in both arms.
Month 12 (52 weeks post-randomization)

Autres mesures de résultats

Mesure des résultats
Description de la mesure
Délai
Change in Macular Superficial Capillary Plexus Perfusion Density on OCT-A
Délai: Baseline (Month 0) and Month 12 (pre- and post-intervention comparison)
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.
Baseline (Month 0) and Month 12 (pre- and post-intervention comparison)
Change in Peripapillary Radial Capillary Plexus Perfusion Density on OCT-A
Délai: Baseline (Month 0) and Month 12 (pre- and post-intervention comparison)
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.
Baseline (Month 0) and Month 12 (pre- and post-intervention comparison)

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

University of Chicago

Les enquêteurs

  • Chercheur principal: Steven C Quan, OD, University of Chicago

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Estimé)

1 juin 2027

Achèvement primaire (Estimé)

30 septembre 2029

Achèvement de l'étude (Estimé)

31 octobre 2029

Dates d'inscription aux études

Première soumission

2 septembre 2026

Première soumission répondant aux critères de contrôle qualité

2 septembre 2026

Première publication (Réel)

8 septembre 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

11 septembre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

9 septembre 2026

Dernière vérification

1 septembre 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • IRB26-0972
  • IND Number: 184022 (Autre identifiant: U.S. Food and Drug Administration (FDA))

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

OUI

Description du régime IPD

De-identified individual participant data supporting primary and secondary outcome analyses will be made available following study completion and primary manuscript publication, subject to University of Chicago data governance policies and a data use agreement. Requests will be reviewed by the principal investigator.

Délai de partage IPD

Beginning 12 months after primary study results publication

Critères d'accès au partage IPD

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.

Type d'informations de prise en charge du partage d'IPD

  • PROTOCOLE D'ÉTUDE
  • SÈVE
  • CIF

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Oui

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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