Pilot Study of the Efficacy of Nicotinamide (Vitamin B3) in Leber's Hereditary Optic Neuropathy

Official title

NICOLHON - Pilot Study of the Efficacy of Nicotinamide (Vitamin B3) in Leber's Hereditary Optic Neuropathy

Overview

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.

Interventions

• Drug Nicotinamide treatment
  All participants receive nicotinamide (vitamin B3) at a dose of 2 grams per day for 12 months. This is an open-label, single-arm study where each patient serves as their own control. Outcomes will be compared longitudinally to baseline measurements.

Primary outcome measures

• 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. [Time frame: inclusion, 3 months, 6 months, 9 months, and 12 months]

Secondary outcome measures (11)

• The effectiveness of treatment on the progression of corrected distance visual acuity [Time frame: 12 months]
• The effectiveness of treatment on the evolution of corrected distance visual acuity [Time frame: inclusion, 3 months, 6 months, 9 months and 12 months]
• The effectiveness of treatment on the evolution of corrected near visual acuity [Time frame: inclusion, 3 months, 6 months, 9 months and 12 months]
• The effectiveness of treatment on the evolution of Campimetric deficits [Time frame: inclusion, 3 months, 6 months, 9 months and 12 months]
• The effectiveness of treatment on the evolution of the appearance of visual field [Time frame: inclusion, 3 months, 6 months, 9 months and 12 months]
• The effectiveness of treatment on the evolution of optic nerve fiber layer (RNFL) thickness [Time frame: inclusion, 3 months, 6 months, 9 months and 12 months]
• The effectiveness of treatment on the evolution of retinal ganglion cell complex (GCC) [Time frame: inclusion, 3 months, 6 months, 9 months and 12 months]
• The effectiveness of treatment on the evolution of Patients' quality of life [Time frame: inclusion and 12 months]
• Biological efficacy of treatment [Time frame: 3 and 12 months]
• Treatment tolerance on Hepatic toxicity [Time frame: Inclusion, 3 months, 6 months, 9 months, 12 months]
• Treatment tolerance in the macula [Time frame: Inclusion, 3 months, 6 months, 9 months, 12 months]

Eligibility criteria

Inclusion criteria

• 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).

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

France · 1 center

• Angers University Hospital — Angers

Identifiers

NCT: NCT07258667 · 49RC25_0169 · 2025-524343-13-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗