Nicotinamide and Pyruvate for Open Angle Glaucoma: A Randomized Clinical Study

NCT ID: NCT05695027

Last Updated: 2025-11-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

250 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-03-14

Study Completion Date

2028-01-31

Brief Summary

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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).

Detailed Description

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Glaucoma is the leading cause of irreversible blindness worldwide. The most important test to detect progression is visual field testing or standard automated perimetry (SAP). The natural course of glaucoma includes a decline in visual function that matches optic nerve structural changes over time.

Both in clinical practice and in clinical trials, individuals undergo visual field testing at regular intervals in order to define whether progressive changes have occurred as well as the rapidity of change. Visual field results are highly variable within and between sessions, partly due to its subjective nature, which ultimately depends upon the test reliability, individuals' level of experience with the test, variability due to disease severity, and, importantly, the level of individual attentiveness during the test. Therefore, numerous attempts have been made to try to optimize individuals' performance during the test. Some of the approaches reported to date are listening to classical music mitigating background noise and use of nutritional supplements.

Recent studies have suggested that over-the-counter medications such as nicotinamide (vitamin B3) and pyruvate can also improve the performance during this test. The investigators are doing this research study to find out if taking nutritional supplements (vitamin B3 and pyruvate) available over- the-counter can help slow the rate of glaucomatous visual field progression compared to placebo.

Conditions

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Primary Open Angle Glaucoma

Keywords

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nutritional supplement nicotinamide pyruvate

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

1:1 Randomization
Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

SINGLE

Participants
Labels on supplements are A and B only.

Study Groups

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Nicotinamide and Pyruvate

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

Group Type EXPERIMENTAL

Dietary supplements - Nicotinamide and Pyruvate

Intervention Type DRUG

Nutritional supplements

Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo

Interventions

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Dietary supplements - Nicotinamide and Pyruvate

Nutritional supplements

Intervention Type DRUG

Placebo

Placebo

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Willing and able to provide informed consent for participation in the study.
2. Between 35 and 85 years of age.
3. Only one eligible eye per patient will be enrolled. If both eyes qualify, study eye will be elected based on the following characteristics (in order of most to least important): 1) disc hemorrhage, 2) higher intraocular pressure (IOP), 3) without previous filtering surgery, 4) better visual acuity. If both eyes meet these four criteria equally, then the study eye will be determined by random assignment.
4. Have a confirmed diagnosis of primary open-angle glaucoma, pseudoexfoliative glaucoma, or pigmentary glaucoma.
5. If there is a prior reliable 24-2, the MD should be better than -20dB.
6. Able to perform reliable visual field testing with 24-2 Swedish Interactive Threshold Algorithm (SITA)-Standard SAP (defined as false positive rates \<15%, false negative rates \<30%) at the most recent office visit.
7. Have best corrected visual acuity better than or equal to 20/40 in the study eye.
8. Have an IOP (treated or untreated) ≥ 14 mmHg and within 24 months of the baseline visit and one instance of historical IOP ≥ 16 mmHg by patient report or chart.

Exclusion Criteria

1. Glaucoma or cataract surgery anticipated in the next 18 months.
2. Have a diagnosis of significant cataract or media opacity affecting the visual field test or imaging studies.
3. Have a diagnosis of dementia, Alzheimer's, or other neurological disease.
4. Have an inability to take or intolerance to nicotinamide and/or pyruvate.
5. Have undergone incisional glaucoma surgery (trabeculectomy, glaucoma drainage implant, or Xen Gel Stent) within the last 12 months. Phacoemulsification ± canalicular micro-invasive glaucoma surgery (MIGS) is acceptable if performed ≥ 4 months prior to study entry.
6. Prior complicated cataract surgery (e.g., vitrectomy, etc)
7. Have a functioning trabeculectomy, glaucoma drainage implant, or Xen Gel Stent (defined as being on 0-1 glaucoma medications). If these surgeries have failed and the patient is on ≥ 2 classes of glaucoma medication and meets all other entry criteria, he/she is eligible).
8. Retinal pathology that significantly affects visual acuity (worse than 20/40) or visual field.
9. Refractive disorders and disorders other than glaucoma known to affect the visual field (VF) and macular optical coherence tomography (OCT) imaging (e.g., epiretinal membrane, cystoid macular edema, pathologic myopia, cylinder \> 3 diopters, prior history of pars plana vitrectomy with internal limiting membrane peel).
10. IOP at screening or baseline visit ≥ 25 mmHg.
11. Have a known history of liver disease.
12. Are pregnant or are planning to become pregnant.
Minimum Eligible Age

35 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Stanford University

OTHER

Sponsor Role collaborator

Columbia University

OTHER

Sponsor Role lead

Responsible Party

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Aakriti G. Shukla

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Aakriti G. Shukla, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

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Stanford University Department of Ophthalmology

Palo Alto, California, United States

Site Status

ColumbiaDoctors Ophthalmology - 880 Third Avenue

New York, New York, United States

Site Status

Columbia University Irving Medical Center - 622 W 168th St

New York, New York, United States

Site Status

Countries

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United States

References

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Williams PA, Harder JM, Foxworth NE, Cochran KE, Philip VM, Porciatti V, Smithies O, John SW. Vitamin B3 modulates mitochondrial vulnerability and prevents glaucoma in aged mice. Science. 2017 Feb 17;355(6326):756-760. doi: 10.1126/science.aal0092.

Reference Type BACKGROUND
PMID: 28209901 (View on PubMed)

Shukla AG, Cioffi GA, Liebmann JM. Drug-Induced Liver Injury During a Glaucoma Neuroprotection Clinical Trial. J Glaucoma. 2024 Aug 1;33(8):e58-e59. doi: 10.1097/IJG.0000000000002394. Epub 2024 Mar 28.

Reference Type DERIVED
PMID: 38536128 (View on PubMed)

Liebmann JM, Cioffi GA. Nicking Glaucoma with Nicotinamide? N Engl J Med. 2017 May 25;376(21):2079-2081. doi: 10.1056/NEJMcibr1702486. No abstract available.

Reference Type BACKGROUND
PMID: 28538117 (View on PubMed)

De Moraes CG, John SWM, Williams PA, Blumberg DM, Cioffi GA, Liebmann JM. Nicotinamide and Pyruvate for Neuroenhancement in Open-Angle Glaucoma: A Phase 2 Randomized Clinical Trial. JAMA Ophthalmol. 2022 Jan 1;140(1):11-18. doi: 10.1001/jamaophthalmol.2021.4576.

Reference Type BACKGROUND
PMID: 34792559 (View on PubMed)

Williams PA, Harder JM, Foxworth NE, Cardozo BH, Cochran KE, John SWM. Nicotinamide and WLDS Act Together to Prevent Neurodegeneration in Glaucoma. Front Neurosci. 2017 Apr 25;11:232. doi: 10.3389/fnins.2017.00232. eCollection 2017.

Reference Type BACKGROUND
PMID: 28487632 (View on PubMed)

Other Identifiers

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AAAU0211

Identifier Type: -

Identifier Source: org_study_id