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

NCT07258667 | Not Yet Recruiting Phase 1

• 2 other identifiers: 49RC25_01692025-524343-13-00
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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.

  inclusion, 3 months, 6 months, 9 months, and 12 months

Secondary Outcomes (11)

• 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

Study Arms (1)

Nicotinamide

EXPERIMENTAL

Drug: Nicotinamide treatment

Interventions

Nicotinamide treatment 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.

Nicotinamide

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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).

You may not qualify if:

• 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.
• Current or recent treatment with idebenone (within 3 months).
• Severe associated ophthalmologic disease (e.g., advanced glaucoma, retinal pathology).
• Patients treated with gene therapy.
• 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.

Sponsors & Collaborators

• University Hospital, Angers: lead

Study Sites (1)

Angers University Hospital

Angers, 49933, France

Location

MeSH Terms

Conditions

Optic Atrophy, Hereditary, Leber; Mitochondrial Diseases; Optic Nerve Diseases

Condition Hierarchy (Ancestors)

Optic Atrophies, Hereditary; Optic Atrophy; Cranial Nerve Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Eye Diseases, Hereditary; Eye Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Pacal Reynier, Professor

CONTACT

0241355542; PaReynier@chu-angers.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2025
• First Posted: December 2, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: The data will be shared after signing a negotiated data transfer agreement ( data access agreement), for the duration specified in the agreement
• Access Criteria: The data will be made available via secure transfer (sharing platform approved by the university hospital: BlueFiles or Oodrive).

Locations

FR (1)