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

NCT05695027 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: AAAU0211
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 3

Brief Summary

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).

Conditions

Primary Open Angle Glaucoma

Keywords

nutritional supplement; nicotinamide; pyruvate

Outcome Measures

Primary Outcomes (2)

• Change in visual field results based on pointwise and global metrics

  The primary outcome in this study are changes in visual field results based on pointwise and global metrics between intervention and placebo groups.

  87 weeks

• Change in retinal nerve fiber and ganglion cell layer thickness

  The primary outcome in this study are changes in retinal nerve fiber and ganglion cell layer thickness as assessed by optical coherence tomography testing between intervention and placebo groups.

  87 weeks

Study Arms (2)

Nicotinamide and Pyruvate

EXPERIMENTAL

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

Drug: Dietary supplements - Nicotinamide and Pyruvate

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Dietary supplements - Nicotinamide and Pyruvate DRUG

Nutritional supplements

Nicotinamide and Pyruvate

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 35 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide informed consent for participation in the study.
• Between 35 and 85 years of age.
• 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.
• Have a confirmed diagnosis of primary open-angle glaucoma, pseudoexfoliative glaucoma, or pigmentary glaucoma.
• If there is a prior reliable 24-2, the MD should be better than -20dB.
• 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.
• Have best corrected visual acuity better than or equal to 20/40 in the study eye.
• 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.

You may not qualify if:

• Glaucoma or cataract surgery anticipated in the next 18 months.
• Have a diagnosis of significant cataract or media opacity affecting the visual field test or imaging studies.
• Have a diagnosis of dementia, Alzheimer's, or other neurological disease.
• Have an inability to take or intolerance to nicotinamide and/or pyruvate.
• 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.
• Prior complicated cataract surgery (e.g., vitrectomy, etc)
• 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).
• Retinal pathology that significantly affects visual acuity (worse than 20/40) or visual field.
• 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).
• IOP at screening or baseline visit ≥ 25 mmHg.
• Have a known history of liver disease.
• Are pregnant or are planning to become pregnant.

Sponsors & Collaborators

• Columbia University: lead
• Stanford University: collaborator

Study Sites (3)

Stanford University Department of Ophthalmology

Palo Alto, California, 94303, United States

Location

ColumbiaDoctors Ophthalmology - 880 Third Avenue

New York, New York, 10022, United States

Location

Columbia University Irving Medical Center - 622 W 168th St

New York, New York, 10032, United States

Location

Related Publications (5)

• 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.

  PMID: 28538117 BACKGROUND

• 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.

  PMID: 34792559 BACKGROUND

• 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.

  PMID: 28487632 BACKGROUND

• 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.

  PMID: 28209901 BACKGROUND

• 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.

  PMID: 38536128 DERIVED

MeSH Terms

Conditions

Glaucoma, Open-Angle

Interventions

Pyruvic Acid

Condition Hierarchy (Ancestors)

Glaucoma; Ocular Hypertension; Eye Diseases

Intervention Hierarchy (Ancestors)

Pyruvates; Keto Acids; Carboxylic Acids; Organic Chemicals

Study Officials

• Aakriti G. Shukla, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Labels on supplements are A and B only.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 1:1 Randomization

Study Record Dates

• First Submitted: November 22, 2022
• First Posted: January 23, 2023
• Study Start: March 14, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): January 1, 2028
• Last Updated: November 12, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)