Nicotinamide + Pyruvate for Open-Angle Glaucoma

Recruiting at 3 trial locations

Overseen By Lisa A. Hark, PhD, MBA

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Columbia University

Must be taking: Glaucoma medications

Disqualifiers: Cataract, Dementia, Neurological disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 87 weeks

250 Participants Needed

Trial Summary

What is the purpose of this trial?

The objective of this study is to determine if a combination of oral nicotinamide and pyruvate (N\&P) can maintain eye health as compared to placebo while standard-of-care intraocular pressure-lowering glaucoma medications are used to treat glaucoma. A total of up to 188 participants will be enrolled and randomized 1:1 to receive N\&P or placebo for 87 weeks (20 months). Participants will be followed for a total of 91 weeks (21 months).

Do I need to stop my current medications for this trial?

The trial does not specify that you need to stop taking your current glaucoma medications. In fact, it mentions that standard-of-care intraocular pressure-lowering medications will continue to be used during the study.

What data supports the effectiveness of the drug Nicotinamide and Pyruvate for treating open-angle glaucoma?

Research suggests that nicotinamide, a component of the drug, may help protect eye cells from damage in glaucoma by supporting cell function and reducing stress on the cells. Studies on similar compounds have shown potential benefits in slowing down the progression of glaucoma. ^{1 2 3 4 5}

Is Nicotinamide and Pyruvate safe for humans?

The research suggests that nicotinamide (a form of vitamin B3) is being studied for its potential benefits in treating glaucoma, and it is generally considered safe as it is a vitamin supplement. However, more research is needed to fully understand its safety and appropriate dosing in humans. ^{1 2 3 6 7}

How does the drug Nicotinamide and Pyruvate differ from other treatments for open-angle glaucoma?

Nicotinamide and Pyruvate is unique because it targets the underlying causes of glaucoma, such as mitochondrial dysfunction and oxidative stress, by replenishing nicotinamide adenine dinucleotide (NAD) levels, which are crucial for cell health. Unlike traditional treatments that focus on lowering eye pressure, this drug aims to protect retinal cells directly, potentially slowing disease progression even when eye pressure is controlled. ^{1 2 3 4 7}

Research Team

Aakriti G. Shukla, MD

Principal Investigator

Columbia University

Eligibility Criteria

Adults aged 40-85 with primary open-angle, pseudoexfoliative, or pigmentary glaucoma can join this study. They must be able to consent, have one qualifying eye with specific characteristics if both are eligible, and perform reliable visual field tests. Participants should not be on certain supplements or have had recent incisional glaucoma surgery.

Inclusion Criteria

Willing and able to provide informed consent for participation in the study

I have been diagnosed with a specific type of glaucoma.

I am willing to stop taking any supplements for the study period.

Exclusion Criteria

I had glaucoma surgery in the last year.

I have been diagnosed with dementia, Alzheimer's, or another neurological disease.

I have been diagnosed with a significant cataract affecting my vision.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either nicotinamide and pyruvate or placebo for 87 weeks

87 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Nicotinamide and Pyruvate
• Placebo

Trial Overview The trial is testing whether oral nicotinamide and pyruvate supplements can help maintain eye health in glaucoma patients compared to a placebo. All participants will continue their usual glaucoma medications during the 21-month study period.

Participant Groups

Group I: Nicotinamide and Pyruvate Experimental Treatment 1 Intervention

The N\&P group will receive nicotinamide and pyruvate for 87 weeks (20 months).

Group II: Placebo Placebo Group 1 Intervention

The placebo group will receive placebo for 87 weeks (20 months).

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Stanford University

Collaborator

Trials

2,527

Recruited

17,430,000+

Findings from Research

Glaucoma and age-related macular degeneration are major causes of irreversible blindness, and current treatments only manage symptoms rather than addressing the underlying causes of these neurodegenerative diseases.

The review suggests that low levels of nicotinamide adenine dinucleotide (NAD) may contribute to the disease mechanisms, and that providing external sources of NAD could become a new therapeutic approach for treating these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential Therapeutic Benefit of NAD+ Supplementation for Glaucoma and Age-Related Macular Degeneration. Cimaglia, G., Votruba, M., Morgan, JE., et al.[2021]

Individuals with primary open-angle glaucoma (POAG) have significantly lower plasma concentrations of nicotinamide compared to age- and sex-matched controls, with reductions of about 30-33%.

These findings suggest that nicotinamide supplementation could be a potential therapeutic strategy for POAG, but further research with larger groups is necessary to confirm these results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide Deficiency in Primary Open-Angle Glaucoma. Kouassi Nzoughet, J., Chao de la Barca, JM., Guehlouz, K., et al.[2019]

Vitamin B3 compounds, nicotinamide (NAM) and nicotinamide riboside (NR), are being explored as potential adjuvant therapies for glaucoma, aiming to protect retinal ganglion cells (RGCs) and prevent optic nerve damage.

These compounds serve as precursors to nicotinamide adenine dinucleotide (NAD), which is crucial for cell function and may help reduce RGC vulnerability to stressors like increased intraocular pressure, especially in patients who continue to progress despite adequate IOP control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of Nicotinamide and Nicotinamide riboside as an adjunct therapy in the treatment of glaucoma. Goulart Nacácio E Silva, S., Occhiutto, ML., Costa, VP.[2023]

Systemic administration of nicotinamide riboside (NR), a precursor to NAD+, significantly enhances the survival of retinal ganglion cells (RGCs) in both acute and chronic models of RGC damage in mice, indicating its potential as a protective treatment for glaucoma.

NR treatment not only preserved RGC function but also reduced retinal inflammation, suggesting a dual mechanism of action that could be beneficial in managing glaucoma, even when intraocular pressure is controlled.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic Treatment with Nicotinamide Riboside Is Protective in Two Mouse Models of Retinal Ganglion Cell Damage. Zhang, X., Zhang, N., Chrenek, MA., et al.[2021]

This study is a randomized controlled trial involving 125 patients with primary open-angle glaucoma (POAG) to evaluate the effectiveness of nicotinamide riboside (NR) in slowing optic nerve degeneration over 24 months.

The primary outcome is the rate of retinal nerve fiber layer (RNFL) thinning, which will provide a more objective measure of neuroprotection compared to traditional visual field tests, potentially allowing for quicker assessment of treatment effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide riboside as a neuroprotective therapy for glaucoma: study protocol for a randomized, double-blind, placebo-control trial. Leung, CKS., Ren, ST., Chan, PPM., et al.[2022]

Nicotinamide (vitamin B3) shows promise as a potential treatment for glaucoma, with studies indicating a strong link between low levels of NAD+ and retinal ganglion cell dysfunction, which is critical in glaucoma.

Research suggests that nicotinamide supplementation may improve retinal ganglion cell function in both animal models and human studies, but further investigation is necessary to establish its efficacy, optimal dosing, and safety for broader use in glaucoma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of NAD+ and Nicotinamide (Vitamin B3) in Glaucoma: A Literature Review. Pietris, J.[2022]

Nicotinamide (NAM) treatment improved retinal vasculature in ocular hypertensive rats, showing significant increases in various vessel parameters, indicating its potential to prevent retinal vascular damage in glaucoma.

In human subjects, NAM treatment resulted in small but significant increases in retinal perfusion density in both glaucoma patients and healthy controls, suggesting a beneficial effect on retinal blood flow.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide Prevents Retinal Vascular Dropout in a Rat Model of Ocular Hypertension and Supports Ocular Blood Supply in Glaucoma Patients. Gustavsson, ST., Enz, TJ., Tribble, JR., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Potential Therapeutic Benefit of NAD+ Supplementation for Glaucoma and Age-Related Macular Degeneration. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Nicotinamide Deficiency in Primary Open-Angle Glaucoma. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

The use of Nicotinamide and Nicotinamide riboside as an adjunct therapy in the treatment of glaucoma. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Systemic Treatment with Nicotinamide Riboside Is Protective in Two Mouse Models of Retinal Ganglion Cell Damage. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Nicotinamide riboside as a neuroprotective therapy for glaucoma: study protocol for a randomized, double-blind, placebo-control trial. [2022]

6. Japan pubmed.ncbi.nlm.nih.gov

The Role of NAD+ and Nicotinamide (Vitamin B3) in Glaucoma: A Literature Review. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Nicotinamide Prevents Retinal Vascular Dropout in a Rat Model of Ocular Hypertension and Supports Ocular Blood Supply in Glaucoma Patients. [2023]