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

NCT ID: NCT07258667

Last Updated: 2025-12-18

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-04-30
• Study Completion Date: 2028-04-30

Brief Summary

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.

Conditions

Leber Hereditary Optic Neuropathy (LHON); Leber's Hereditary Optic Neuropathy (LHON); Mitochondrial Disease; Optic Nerve Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Nicotinamide

Group Type: EXPERIMENTAL

Nicotinamide treatment

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Angers

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Angers University Hospital

Angers, , France

Countries

France

Central Contacts

Pacal Reynier, Professor

Role: CONTACT

Phone: 0241355542

Email: PaReynier@chu-angers.fr

Facility Contacts

Pascal Reynier, Professor

Role: primary

Other Identifiers

2025-524343-13-00

Identifier Type: CTIS

Identifier Source: secondary_id

49RC25_0169

Identifier Type: -

Identifier Source: org_study_id