Department of Ophthalmology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
Hong Kong Eye Hospital, Hong Kong, People's Republic of China.
Trials. 2022 Jan 17;23(1):45. doi: 10.1186/s13063-021-05968-1.
Whereas lowering the intraocular pressure (IOP) can slow optic nerve degeneration in glaucoma, many patients with glaucoma continue to develop progressive loss in vision despite a significant reduction in IOP. No treatment has been shown to be effective for neuroprotection in glaucoma. We set out to conduct a randomized controlled trial to investigate whether nicotinamide riboside (NR), a nicotinamide adenine dinucleotide precursor, is effective to slow optic nerve degeneration in patients with primary open-angle glaucoma (POAG). We hypothesize that patients treated with NR have a slower rate of progressive retinal nerve fiber layer (RNFL) thinning compared with those treated with placebo.
This is a randomized, double-blind, placebo-controlled, parallel-group, multi-center study including 125 patients with POAG. Patients will be randomized to receive 300 mg NR or placebo for 24 months. Clinical examination, optical coherence tomography imaging of the RNFL, and visual field (VF) test will be performed at the baseline, 1 month, 4 months, and then at 2-month intervals until 24 months. The primary outcome measure is the rate of RNFL thinning measured over 24 months. The secondary outcome measures include (1) time to VF progression, (2) time to progressive RNFL/ganglion cell inner plexiform layer (GCIPL) thinning, and (3) the rate of change of VF sensitivity over 24 months (to investigate neuroprotection) and 1 month (to investigate neuroenhancement). The rates of RNFL thinning and VF sensitivity decline between treatment groups will be compared with linear mixed modeling. Survival analysis will be performed to compare the differences in time from baseline to VF progression and time from baseline to progressive RNFL/GCIPL thinning between treatment groups using Cox proportional hazards models.
Outcome measures in glaucoma neuroprotection trials have been centered on the detection of VF progression, which may take years to develop and confirm. In addition to addressing whether NR has a neuroprotective/neuroenhancement effect in glaucoma patients, this study will demonstrate the feasibility of studying neuroprotection in a relatively short trial period (24 months) by comparing the rates of progressive RNFL thinning, a more reproducible and objective outcome measure compared with VF endpoints, between treatment groups.
Chinese Clinical Trial Registry 1900021998.
降低眼内压（IOP）可以减缓青光眼视神经变性，但许多青光眼患者尽管 IOP 显著降低，仍继续出现进行性视力丧失。目前尚无有效的治疗方法可用于青光眼的神经保护。我们着手进行一项随机对照试验，以研究烟酰胺核糖（NR），一种烟酰胺腺嘌呤二核苷酸前体，是否可有效减缓原发性开角型青光眼（POAG）患者的视神经变性。我们假设与接受安慰剂治疗的患者相比，接受 NR 治疗的患者视网膜神经纤维层（RNFL）进行性变薄的速度较慢。
这是一项随机、双盲、安慰剂对照、平行分组、多中心研究，纳入 125 例 POAG 患者。患者将被随机分为接受 300mg NR 或安慰剂治疗 24 个月。在基线、1 个月、4 个月以及之后每 2 个月进行临床检查、RNFL 的光学相干断层扫描成像和视野（VF）检查，直至 24 个月。主要观察指标为 24 个月时 RNFL 变薄的速率。次要观察指标包括（1）VF 进展时间，（2）进行性 RNFL/神经节细胞内丛状层（GCIPL）变薄时间，以及（3）24 个月时 VF 敏感性的变化率（以研究神经保护）和 1 个月时（以研究神经增强）。将通过线性混合模型比较治疗组之间的 RNFL 变薄率和 VF 敏感性下降率。使用 Cox 比例风险模型进行生存分析，以比较治疗组之间从基线到 VF 进展和从基线到进行性 RNFL/GCIPL 变薄的时间差异。
青光眼神经保护试验的结局指标一直集中在 VF 进展的检测上，而 VF 进展可能需要数年时间才能发展和确认。除了确定 NR 在青光眼患者中是否具有神经保护/神经增强作用外，本研究还将通过比较治疗组之间更具重复性和客观性的 RNFL 进行性变薄率，在相对较短的试验期（24 个月）内证明研究神经保护的可行性，与 VF 终点相比，这是一种更可靠的结果指标。
中国临床试验注册中心 1900021998。
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