Nicotinamide Levels in Serum, Aqueous Humor, and Tear Film in Glaucoma and Correlations With Mitochondrial Damage-Associated Molecular Patterns (mtDAMPs) and Senescence-Associated Secretory Phenotype (SASP)

Conditions

• Glaucoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Accepted

Interventions

• Nicotinamide Tablet — DIETARY_SUPPLEMENT
  One nicotinamide tablet per day during the month preceding surgery

Study Details

Background Glaucoma is a multifactorial, chronic, and progressive eye disease characterized by the irreversible loss of retinal ganglion cells (RGCs). It is the second leading cause of blindness globally, with approximately 76 million patients affected in 2020, a number expected to rise to 120 million in the coming decades, especially in Africa and Asia. Elevated intraocular pressure (IOP) is a significant risk factor for glaucoma, and its reduction remains the only scientifically proven approach to slowing visual function decline. However, many glaucoma patients continue to experience visual loss even with IOP values within the normal range, due to the disease's multifactorial nature. Besides IOP reduction, there is a need for direct neuroprotection to address other factors causing RGC damage. Mitochondrial dysfunction has emerged as a critical early factor in RGC damage, making glaucoma, at least in part, resemble a mitochondrial disease. Mitochondria play a key role in cellular functions such as energy production, redox metabolism, and maintaining mitochondrial function. In glaucomatous conditions, mitochondrial damage leads to the release of mitochondrial damage-associated molecular patterns (mtDAMPs), triggering chronic inflammation and tissue damage. This inflammation is exacerbated by the Senescence-Associated Secretory Phenotype (SASP), a process where senescent cells secrete bioactive molecules that contribute to cellular dysfunction and glaucoma progression. Among potential neuroprotective approaches, nicotinamide (NAM) and its precursor nicotinamide riboside (NR) are gaining attention. These compounds support mitochondrial function and NAD production, which is essential for cellular vitality. Research indicates that reductions in NAM levels correlate with glaucoma progression. For instance, studies have shown that NAD precursors may prevent or delay RGC degeneration, suggesting a promising adjunctive treatment for glaucoma patients. Study Objectives The study aims to measure NAM levels in ocular and non-ocular biological fluids (serum, aqueous humor, and tear fluid) of patients at different stages of glaucoma. The study will correlate NAM concentrations with disease severity and mitochondrial function markers. Furthermore, NAD levels in peripheral blood mononuclear cells (PBMCs) will be assessed to investigate potential biomarkers for glaucoma progression. A secondary objective is to evaluate the impact of dietary supplementation with nicotinamide and nicotinamide riboside (iNAD®) on NAD levels in pharmacologically controlled glaucoma patients. Methods This cross-sectional, case-control, multi-center study involves three universities: University of G. d'Annunzio Chieti-Pescara, University of Pisa, and University of Sassari. Biological fluid analyses will be conducted at the Animal Biology Laboratory affiliated with the University of G. d'Annunzio Chieti-Pescara. Patients will be categorized into four groups: 1. Uncontrolled glaucoma patients scheduled for glaucoma surgery. 2. Controlled glaucoma patients scheduled for cataract surgery. 3. Healthy controls undergoing cataract surgery. 4. Pharmacologically controlled glaucoma patients supplemented with iNAD®. Biological fluids (plasma, PBMCs, tear fluid, and aqueous humor) will be collected for analysis, including measures of NAD, mtDAMPs, and SASP components. These measures aim to provide insights into the molecular mechanisms underlying glaucoma and potential biomarkers for disease progression. Statistical Analysis Sample size estimation was calculated using G\*Power for a priori one-way ANOVA analysis. Assuming a mean NAM concentration of 0.14 μM (SD=0.12) for glaucoma patients and 0.19 μM (SD=0.13) for controls, with a power of 80% and alpha of 0.05, a minimum of 246 patients (82 per group) are required.

Key Dates

First listed

Jun 5, 2025

Start date

Oct 1, 2025

Status verified

May 2025

Primary completion

Dec 31, 2026

Completion

Dec 31, 2026

Study Design

Enrollment

360 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

FACTORIAL

Primary purpose

BASIC_SCIENCE

Arms

• No Intervention: OAG not pharmacologically controlled, receiving MTM and scheduled for filtering glaucoma surgery
  Patients with open-angle glaucoma (OAG) not pharmacologically controlled, receiving maximal tolerated medical therapy and scheduled for filtering glaucoma surgery (stand-alone or combined). To this arm will be administered ophthalmological evaluation, functional stage determination, OCT imaging, sampling and analysis of biological fluids (Plasma and Peripheral Blood Mononuclear Cells (PBMCs) Isolation, Tear Film, Aqueous Humor; NAD Quantification in all biological fluids, mtDAMPS and SASP quantification in PBMCs)
• No Intervention: Pharmacologically controlled OAG scheduled for cataract surgery
  Patients with pharmacologically controlled OAG scheduled for cataract surgery. To this arm will be administered ophthalmological evaluation, functional stage determination, OCT imaging, sampling and analysis of biological fluids (Plasma and Peripheral Blood Mononuclear Cells (PBMCs) Isolation, Tear Film, Aqueous Humor; NAD Quantification in all biological fluids, mtDAMPS and SASP quantification in PBMCs)
• No Intervention: Healthy individuals scheduled for cataract surgery
  Healthy individuals scheduled for cataract surgery. To this arm will be administered ophthalmological evaluation, functional stage determination, OCT imaging, sampling and analysis of biological fluids (Plasma and Peripheral Blood Mononuclear Cells (PBMCs) Isolation, Tear Film, Aqueous Humor; NAD Quantification in all biological fluids, mtDAMPS and SASP quantification in PBMCs)
• Experimental: Pharmacologically controlled OAG patients scheduled for cataract surgery and treated with iNAD
  Pharmacologically controlled OAG patients scheduled for cataract surgery and treated with iNAD. To this arm will be administered iNAD during the month preceding surgery and ophthalmological evaluation, functional stage determination, OCT imaging, sampling and analysis of biological fluids (Plasma and Peripheral Blood Mononuclear Cells (PBMCs) Isolation, Tear Film, Aqueous Humor; NAD Quantification in all biological fluids, mtDAMPS and SASP quantification in PBMCs)

Primary Outcome Measure

Nicotinamide levels measurement in biologic fluids [ Time Frame: Day 1 ]

Central Contacts

• Luca Agnifili, Principal Investigator
  +390871357219
  [email protected]

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