NICOLHON - Pilot Study of the Efficacy of Nicotinamide (Vitamin B3) in Leber's Hereditary Optic Neuropathy
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- To evaluate the efficacy of administering 2 grams per day of nicotinamide for 12 months in patients who have developed NOHL due to an m.11778G>A or m.3460G>A mutation within the last 18 months.
研究概览
简要总结
Leber Hereditary Optic Neuropathy (LHON) is a rare genetic disease that causes sudden and severe vision loss, usually in young adults. It is linked to mutations in mitochondrial DNA that impair energy production in retinal ganglion cells, leading to degeneration of the optic nerve. Currently, treatment options are very limited and often ineffective. Recent research has shown that patients with LHON have lower levels of nicotinamide (vitamin B3), a key molecule for mitochondrial energy metabolism. Nicotinamide is a precursor of NAD, an essential cofactor for cellular energy production. Experimental studies and clinical trials in related optic nerve diseases suggest that nicotinamide may protect retinal ganglion cells. Our hypothesis is that supplementation with high-dose nicotinamide could restore NAD levels, support mitochondrial activity, and help preserve or improve vision in LHON. This pilot study will evaluate the effectiveness and safety of oral nicotinamide (2 grams per day for 12 months) in patients who developed LHON within the past 18 months and carry one of the two most severe mutations (m.11778G>A or m.3460G>A). The main goal is to measure changes in visual acuity over time using standardized eye charts. Secondary objectives include assessing visual fields, retinal structure by optical coherence tomography (OCT), blood nicotinamide levels, and quality of life. Liver function will be monitored to ensure safety. If this study shows promising results, it could pave the way for a larger randomized trial and ultimately offer a new therapeutic option.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged 16 years or older.
- •Diagnosis of Leber Hereditary Optic Neuropathy (LHON) due to a confirmed mitochondrial DNA mutation m.11778G>A or m.3460G>A.
- •Onset of LHON symptoms less than 18 months before inclusion.
- •Naïve to nicotinamide treatment for at least 3 months prior to inclusion.
- •Able to take oral medication and comply with study procedures.
- •Affiliated with or beneficiary of a social security system.
- •Signed informed consent (or parental consent for minors; assent for minors when applicable).
排除标准
- •Asymptomatic carriers of m.11778G>A or m.3460G>A mutations (no clinical LHON).
- •LHON due to other mitochondrial DNA mutations or nuclear DNA mutations.
- •LHON onset more than 18 months before inclusion.
- •Current or recent treatment with idebenone (within 3 months).
- •Severe associated ophthalmologic disease (e.g., advanced glaucoma, retinal pathology).
- •Patients treated with gene therapy.
- •Elevated liver enzymes (ASAT and/or ALAT > 2× upper normal limit) at screening or within 2 months prior to inclusion.
- •Pregnant, breastfeeding, or postpartum women.
- •Known contraindication to nicotinamide or allergy/intolerance to lactose or galactose.
- •Persons deprived of liberty by judicial or administrative decision.
- •Subjects under legal protection or psychiatric care under constraint.
- •Unable to provide informed consent.
- •Participation in another interventional study affecting LHON management.
- •Any condition that, in the investigator's judgment, could compromise patient safety or study integrity.
研究组 & 干预措施
Nicotinamide
干预措施: Nicotinamide treatment (Drug)
结局指标
主要结局
To evaluate the efficacy of administering 2 grams per day of nicotinamide for 12 months in patients who have developed NOHL due to an m.11778G>A or m.3460G>A mutation within the last 18 months.
时间窗: inclusion, 3 months, 6 months, 9 months, and 12 months
Evaluation by the change in corrected distance visual acuity measured eye by eye on an ETDRS (Early Treatment Diabetic Retinopathy Study) scale over the entire follow-up period.
次要结局
- Treatment tolerance in the macula(Inclusion, 3 months, 6 months, 9 months, 12 months)
- The effectiveness of treatment on the progression of corrected distance visual acuity(12 months)
- The effectiveness of treatment on the evolution of corrected distance visual acuity(inclusion, 3 months, 6 months, 9 months and 12 months)
- The effectiveness of treatment on the evolution of corrected near visual acuity(inclusion, 3 months, 6 months, 9 months and 12 months)
- The effectiveness of treatment on the evolution of Campimetric deficits(inclusion, 3 months, 6 months, 9 months and 12 months)
- The effectiveness of treatment on the evolution of the appearance of visual field(inclusion, 3 months, 6 months, 9 months and 12 months)
- The effectiveness of treatment on the evolution of optic nerve fiber layer (RNFL) thickness(inclusion, 3 months, 6 months, 9 months and 12 months)
- The effectiveness of treatment on the evolution of retinal ganglion cell complex (GCC)(inclusion, 3 months, 6 months, 9 months and 12 months)
- The effectiveness of treatment on the evolution of Patients' quality of life(inclusion and 12 months)
- Biological efficacy of treatment(3 and 12 months)
- Treatment tolerance on Hepatic toxicity(Inclusion, 3 months, 6 months, 9 months, 12 months)