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

Sponsor

Columbia University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05695027

Collaborator

(none)

188

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

1.6

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Primary Open Angle Glaucoma	Drug: Dietary supplements - Nicotinamide and Pyruvate Drug: Placebo	Phase 2/Phase 3

Detailed Description

A total of 188 participants meeting the inclusion and exclusion criteria will be enrolled for 21 months. Recruitment will be conducted over a 2-year period after IRB approval at the ColumbiaDoctors Ophthalmology and the Harkness Eye Institute at Columbia University Irving Medical Center (CUIMC), New York, NY.

Following the explanation of the study, obtaining written informed consent, completing visit 1 and confirming eligibility, participants will be randomized 1:1 to N&P or placebo. Participants who have been identified as taking any vitamin, mineral, or herbal supplement will be required to discontinue all of these supplement(s) for the duration of the study.

The N&P group will receive containing bottles of nicotinamide and pyruvate, while those randomized to placebo will receive an equal number of capsules/bottles with placebo. All interventions will be dispensed by the CUIMC Research Pharmacy for CUIMC patients. Participants, study personnel and investigators, will be masked to randomization. Participants will be followed for 91 weeks (21 months). Early termination will be allowed for intolerance to the study components or other safety reasons.

After completing a 4-week wash-out period of nutritional supplements (stopping all vitamin/mineral and herbal supplements) and before starting on the interventions, each participant will undergo a baseline visit which will include comprehensive ophthalmic examination with optic disc photography, OCT using Spectralis (Heidelberg Engineering GmBH, Heidelberg, Germany), and intraocular pressure measurements (IOP) (all of which are standard of care by a trained ophthalmic technician. The study eye will be determined as per protocol if both eyes are eligible. Participants will undergo baseline 10-2 Standard Automated Perimetry (SAP) testing in the study eye using the Humphrey Field Analyzer (HFA) with a trained ophthalmic technician for a total of 3 sessions (window ~ 4 weeks).

Thereafter, they will take their assigned intervention for 87 weeks (20 months) and will perform required testing in accordance with the schedule of visits (Section 16, Table 1). 10-2 SAP test will be administered in a clustered fashion at Visit 1, (3 tests per study eye), Visit 2 (week 9, 3 tests per study eye), and Visit 6 (week 87, 3 tests per study eye within 2 weeks). 2 tests in the study eye will be obtained at Visit 3 (week 26) and 5 (week 70), and 1 test will be obtained at Visit 4 (week 48). A 24-2 VF test will be performed at visit 1, visit 4 (week 48) and visit 6 (week 87) as per standard of care. Dilated disc photography will be obtained at study entry and conclusion. Two OCT cube scans of the macula and optic disc will be obtained at each study visit. The fellow eye will be tested according to the standard of care protocol per investigator discretion based on clinical indication.

All visual field tests and imaging studies will be performed by trained technicians who have been working with the investigators in their clinical practice and studies. Study personnel and physicians will be masked to randomization.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

188 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

1:1 Randomization1:1 Randomization

Masking:

Single (Participant)

Masking Description:

Labels on supplements are A and B only.

Primary Purpose:

Supportive Care

Official Title:

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

Anticipated Study Start Date :

Jan 15, 2023

Anticipated Primary Completion Date :

Jan 15, 2025

Anticipated Study Completion Date :

Jan 15, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nicotinamide and Pyruvate Nicotinamide and Pyruvate	Drug: Dietary supplements - Nicotinamide and Pyruvate Nutritional supplements
Placebo Comparator: Placebo Placebo	Drug: Placebo Placebo

Arm

Intervention/Treatment

Experimental: Nicotinamide and Pyruvate

Nicotinamide and Pyruvate

Drug: Dietary supplements - Nicotinamide and Pyruvate

Nutritional supplements

Placebo Comparator: Placebo

Placebo

Drug: Placebo

Placebo

Outcome Measures

Primary Outcome Measures

The primary outcomes in this study are changes in 1) central (10-2) visual field results based on pointwise and global metrics between intervention and placebo groups. [87 weeks]
The primary outcomes in this study are changes in 1) central (10-2) visual field results based on pointwise and global metrics between intervention and placebo groups.
The primary outcomes in this study are changes in 2) retinal nerve fiber and ganglion cell layer thickness as assessed by optical coherence tomography testing between intervention and placebo groups. [87 weeks]
The primary outcomes in this study are changes in 2) retinal nerve fiber and ganglion cell layer thickness as assessed by optical coherence tomography testing between intervention and placebo groups.

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria

Participants are eligible for study participation if they meet each of the following 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 IOP, 3) without previous filtering surgery,

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 10-2, the MD should be better than -15dB.
Able to perform reliable visual field testing with 24-2 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

Participants are not eligible for study participation if they meet any of the following 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 MIGS surgery 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 VF and macular 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ColumbiaDoctors Ophthalmology - 880 Third Avenue	New York	New York	United States	10022
2	Columbia University Irving Medical Center - 635 W 165th St	New York	New York	United States	10032