Comparisons of Nicotinamide Adenine Dinucleotide (NAD) Precursors for Neuroenhancement in Glaucoma Patients
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 138
- 试验地点
- 1
- 主要终点
- Change in visual field sensitivity
研究概览
简要总结
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:
- 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?
- 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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Placebo (Phase I)
干预措施: Placebo (Corn Starch) (Other)
Placebo (Phase II)
干预措施: Placebo (Corn Starch) (Other)
Nicotinamide (Phase I)
干预措施: Nicotinamide (Dietary Supplement)
Nicotinamide Riboside (Phase I)
干预措施: Nicotinamide Riboside (Dietary Supplement)
Nicotinic Acid (Phase II)
干预措施: Nicotinic Acid (Dietary Supplement)
Nicotinamide Mononucleotide (Phase II)
干预措施: Nicotinamide Mononucleotide (Dietary Supplement)
结局指标
主要结局
Change in visual field sensitivity
时间窗: 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.
次要结局
- Blood NA and NAD+ metabolome(2 weeks)
- Change in pattern ERG measurements(2 weeks)
- Retinal nerve fiber layer thickness and defect imaging by optical coherence tomography(2 weeks)
研究者
Christopher Kai Shun Leung
Chairperson and Clinical Professor
The University of Hong Kong