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

Primary Purpose

Primary Open Angle Glaucoma

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Dietary supplements - Nicotinamide and Pyruvate
Placebo
Sponsored by
Columbia University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Primary Open Angle Glaucoma focused on measuring nutritional supplement, nicotinamide, pyruvate

Eligibility Criteria

40 Years - 85 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria Willing and able to provide informed consent for participation in the study. Between 40 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 a 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. Willing to discontinue taking any vitamin/mineral or herbal supplement for the duration of the study. Exclusion Criteria 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.

Sites / Locations

  • ColumbiaDoctors Ophthalmology - 880 Third AvenueRecruiting
  • Columbia University Irving Medical Center - 635 W 165th StRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Nicotinamide and Pyruvate

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Full Information

First Posted
November 22, 2022
Last Updated
July 31, 2023
Sponsor
Columbia University
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1. Study Identification

Unique Protocol Identification Number
NCT05695027
Brief Title
Nicotinamide and Pyruvate for Open Angle Glaucoma: A Randomized Clinical Study
Official Title
Nicotinamide and Pyruvate for Open Angle Glaucoma: A Randomized Clinical Study
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 14, 2023 (Actual)
Primary Completion Date
January 2025 (Anticipated)
Study Completion Date
January 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Columbia University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Open Angle Glaucoma
Keywords
nutritional supplement, nicotinamide, pyruvate

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
1:1 Randomization
Masking
Participant
Masking Description
Labels on supplements are A and B only.
Allocation
Randomized
Enrollment
188 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Nicotinamide and Pyruvate
Arm Type
Experimental
Arm Description
The N&P group will receive nicotinamide and pyruvate for 87 weeks (20 months).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
The placebo group will receive placebo for 87 weeks (20 months).
Intervention Type
Drug
Intervention Name(s)
Dietary supplements - Nicotinamide and Pyruvate
Intervention Description
Nutritional supplements
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Change in visual field results based on pointwise and global metrics
Description
The primary outcome in this study are changes in visual field results based on pointwise and global metrics between intervention and placebo groups.
Time Frame
87 weeks
Title
Change in retinal nerve fiber and ganglion cell layer thickness
Description
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.
Time Frame
87 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria Willing and able to provide informed consent for participation in the study. Between 40 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 a 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. Willing to discontinue taking any vitamin/mineral or herbal supplement for the duration of the study. Exclusion Criteria 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Aakriti G. Shukla, MD
Phone
212-342-4586
Email
ag2965@cumc.columbia.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Lisa A. Hark, PhD, MBA
Phone
212-342-4586
Email
lah112@cumc.columbia.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Aakriti G. Shukla, MD
Organizational Affiliation
Columbia University
Official's Role
Principal Investigator
Facility Information:
Facility Name
ColumbiaDoctors Ophthalmology - 880 Third Avenue
City
New York
State/Province
New York
ZIP/Postal Code
10022
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aakriti Shukla, MD
Phone
212-342-4586
Email
ag2965@cumc.columbia.edu
Facility Name
Columbia University Irving Medical Center - 635 W 165th St
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aakriti G. Shukla, MD
Phone
212-342-4586
Email
ag2965@cumc.columbia.edu

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
28538117
Citation
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.
Results Reference
background
PubMed Identifier
34792559
Citation
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.
Results Reference
background
PubMed Identifier
28487632
Citation
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.
Results Reference
background
PubMed Identifier
28209901
Citation
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.
Results Reference
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Nicotinamide and Pyruvate for Open Angle Glaucoma: A Randomized Clinical Study

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