Glaucoma
Conditions
Keywords
NAD Precursor, Nicotinic Acid, Nicotinamide, Nicotinamide Mononucleotide, Nicotinamide Riboside
Brief summary
The goal of this clinical trial is to determine whether oral supplementation with different nicotinamide adenine dinucleotide (NAD) precursors can improve visual function in adults with primary open-angle glaucoma. The main questions it aims to answer are: 1. Does daily oral administration of equimolar doses of nicotinamide riboside (NR), nicotinamide (NAM), nicotinamide mononucleotide (NMN), or nicotinic acid (NA) improve visual field sensitivity in glaucoma patients over the short term? 2. How do plasma NAD+ metabolite profiles change after administration of each precursor, and do these changes relate to improvements in visual function? Researchers will compare NR, NAM, NMN, NA, and placebo groups to see if any of the NAD precursors lead to greater improvements in visual field sensitivity or changes in blood NAD+ metabolite levels compared to placebo. Participants will: Be randomly assigned to receive one of the four NAD precursors or placebo daily for two weeks. Undergo comprehensive eye examinations, including visual field testing and optical coherence tomography, at baseline and after two weeks. Provide blood samples before and after the intervention for measurement of NAD+ metabolites. Have safety monitored through clinical examination. This study will help identify whether boosting NAD+ levels with specific precursors offers functional benefit in glaucoma, and which blood metabolites may mediate these effects.
Detailed description
This prospective randomized, double-blind, placebo-controlled clinical trial evaluates four nicotinamide adenine dinucleotide (NAD) precursors for neuroenhancement in 138 adults with primary open-angle glaucoma. Participants are randomly assigned to receive daily oral supplementation for one week with equimolar doses of nicotinamide riboside (300 mg), nicotinamide (125 mg), nicotinamide mononucleotide (350 mg), nicotinic acid (125 mg), or placebo. The study assesses short-term changes in visual field sensitivity using Humphrey Field Analyzer 24-2 testing and measures NAD+ metabolite profiles through liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis of plasma and peripheral blood mononuclear cells collected at baseline, pre-dose, and post-dose timepoints. Secondary objectives include comparing pattern electroretinogram nerve fiber layer thickness measurements before and after treatment and analyzing correlations between systemic NAD+ metabolite elevations and functional visual improvements. Blood samples undergo standardized processing with Lymphoprep separation, snap-freezing, and derivatization protocols prior to mass spectrometry analysis using Agilent and Thermo Fisher systems with predefined NAD+ metabolite inclusion lists. Statistical analysis employs linear mixed models to compare within-group and between-group changes, with intention-to-treat principles. The study design addresses gaps in comparative NAD precursor bioavailability data by testing equimolar doses in a targeted glaucoma population, while maintaining double-blinding through computer-generated randomization and masked outcome assessment.
Interventions
DIETARY_SUPPLEMENTNicotinamide Riboside
Oral supplementation of 300mg Nicotinamide Riboside (NR) daily for 2 weeks
DIETARY_SUPPLEMENTNicotinamide
Oral supplementation of 125mg Nicotinamide/Niacinamide (NAM) daily for 2 weeks
DIETARY_SUPPLEMENTNicotinamide Mononucleotide
Oral supplementation of 350mg Nicotinamide Mononucleotide (NMN) daily for 2 weeks
DIETARY_SUPPLEMENTNicotinic Acid
Oral supplementation of 350mg Nicotinic Acid (NA) daily for 2 weeks
OTHERPlacebo (Corn Starch)
Oral supplementation of 300mg Placebo daily for 2 weeks
Sponsors
Christopher Kai Shun Leung
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The participants, investigators, the outcome assessors, and data analysts will be masked before and after assignment to intervention. The subject will be unmasked as per of the request of Principal Investigator in case of serious adverse event or if emergency unblinding is deemed essential for clinical management. All instances of the unblinding will be documented in the study binder. Unmasked subject will exit from the study and resumes normal clinical management.
Intervention model description
NR, NAM, NMN, or NA in mole equivalent amount, or placebo, will be randomly assigned to 138 patients, 23 per group (a total of 4 treatment groups and 2 placebo groups). Each patient will receive a daily dose of 300 mg NR, 125 mg NAM, 350 mg NMN, 125 mg NA or 300 mg placebo (corn starch capsule) at 9 am each day for two weeks. The study will be conducted in 2 phases. In Phase I, participants will be randomized to placebo, NR, or NAM. In Phase II, participants will be randomized to receive, placebo, NA, or NMN.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* glaucoma patients * age ≥ 18 years * best corrected VA ≥20/40 * IOP \<21 mmHg * visual field mean deviation better than -24 dB on standard automated perimetry 24-2 SITA standard
Exclusion criteria
* pathological myopia * diseases that may cause visual field loss or optic disc abnormalities other than glaucoma * inability to perform reliable visual field * suboptimal quality of OCT images * diabetic retinopathy/maculopathy * history of abnormal liver function within 12 months * known allergy to NAD precursor supplement(s) * pregnancy or lactation * use of NAD precursor supplements 14 days prior to baseline.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in visual field sensitivity | 2 weeks | Visual field will be measured with automated static perimetry by the Humphrey Field Analyzer 3 24-2 SITA standard strategy (HFA; Carl Zeiss Meditec). Two reliable visual fields will be obtained for each eye at the baseline examination, with at least 10 minutes of rest in between, and two reliable visual fields will be obtained for each eye at week two. Change in visual field index (VFI) and threshold sensitivity (dB) before and two weeks after intervention between treatment groups will be compared. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Blood NA and NAD+ metabolome | 2 weeks | At baseline, plasma and PBMC samples will be collected on the day of VF test before the intake of NAD precursor or placebo between 9am and 10am. After two weeks of oral administration of NAD+ precursor or placebo, two blood samples will be collected: between 9 am and 10 am (pre-dose), and then between 11am and 12 noon (post-dose). The sample will be processed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and chromatography-tandem mass spectrometry (GC-MS/MS) to measure the amounts of NAD+ metabolites. Changes in NAD metabolites before and 2 weeks after intake of NAD precursors will be compared between treatment groups. |
| Change in pattern ERG measurements | 2 weeks | Pattern Electroretinogram (PERG) will also be performed at baseline and follow-up for every other subject included in the study. Changes in PERG measurements including P50 and N95 amplitudes, before and two weeks after intervention, will be compared between the placebo group and the NAD precursor group. |
| Retinal nerve fiber layer thickness and defect imaging by optical coherence tomography | 2 weeks | At baseline and week two follow-up visits, RNFL imaging will be performed with the Cirrus HD-OCT (Carl Zeiss Meditec) using the optic nerve head (6x6 mm2) cube scan covering both the macula and the parapapillary area (512x256 pixels). Changes in average RNFL thickness before and two weeks after intervention will be compared between treatment groups. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Impact of age on the change in visual field sensitivity | 2 weeks | To investigate whether age is associated with change in VF sensitivities |
Countries
Hong Kong
Contacts
Primary ContactChristopher Kai-shun LEUNG, MD
Backup ContactNate CHAN
Outcome results
None listed