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

Phase 1Not Yet RecruitingNCT07258667

University Hospital, Angers13 enrolled

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Eligibility

Sex: ALLMin age: 16 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

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.

Time frame: inclusion, 3 months, 6 months, 9 months, and 12 months

Secondary Outcomes

The effectiveness of treatment on the progression of corrected distance visual acuity

Measurement eye by eye using the ETDRS scale, taking the nadir (lowest visual acuity reached a few weeks after the onset of NOHL) as the reference value.

Time frame: 12 months

The effectiveness of treatment on the evolution of corrected distance visual acuity

Measurement eye by eye on a Monoyer scale. Reading capital letters at a distance of 5 meters. Each line on the wall-mounted optometric chart corresponds to 1/10 of visual acuity.The dimensions of the letters are such that they measure 5 times the distance of discrimination corresponding to the measured visual acuity.0.4/10 is low visual acuity and 20/10 is good visual acuity.