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NCT Number: NCT07258667

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

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.

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Key information

Conditions

Leber Hereditary Optic Neuropathy (LHON) Congenital, Hereditary, and Neonatal Diseases and Abnormalities Cranial Nerve Diseases Eye Diseases Eye Diseases, Hereditary Genetic Diseases, Inborn Heredodegenerative Disorders, Nervous System Leber's Hereditary Optic Neuropathy (LHON) Metabolic Diseases Mitochondrial Disease Mitochondrial Diseases Nervous System Diseases Neurodegenerative Diseases Nutritional and Metabolic Diseases Optic Atrophies, Hereditary Optic Atrophy Optic Atrophy, Hereditary, Leber Optic Nerve Disease Optic Nerve Diseases

Age range

16 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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.

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.

    Time frame: 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.

Secondary outcomes

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

    Time frame: 12 months

    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.

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

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

    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.

  3. The effectiveness of treatment on the evolution of corrected near visual acuity

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

    Measurement eye by eye on a Parinaud scale; different sizes of typeface is placed at 33cm. The test consists of a text whose paragraphs are written in decreasing font sizes. The result is expressed in P (P1.5 to P50). The higher the P, the poorer the acuity.

  4. The effectiveness of treatment on the evolution of Campimetric deficits

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

    The average and corrected average deviation measured in STAT 30 on an automated visual field

  5. 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

    By the Goldman-type manual

  6. 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

    Measurement by optical coherence tomography (OCT)

  7. 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

    Measurement by optical coherence tomography (OCT)

  8. The effectiveness of treatment on the evolution of Patients' quality of life

    Time frame: inclusion and 12 months

    NEI VFQ 25 questionnaire. Individual scores are recoded and transformed on a scale of 0 to 100, where 100 represents the best possible functioning and 0 the worst. An average score is calculated for each of the 12 subscales.

  9. Biological efficacy of treatment

    Time frame: 3 and 12 months

    Nicotinamide levels in patients' blood

  10. Treatment tolerance on Hepatic toxicity

    Time frame: Inclusion, 3 months, 6 months, 9 months, 12 months

    Transaminase levels

  11. Treatment tolerance in the macula

    Time frame: Inclusion, 3 months, 6 months, 9 months, 12 months

    Measurement by optical coherence tomography

Study contacts

Contact information is provided by the study sponsor or research team.

Pacal Reynier, Professor

CONTACT

[email protected]

0241355542

Sponsors and collaborators

Lead sponsor

University Hospital, Angers

Other Gov

Registry information

Official study title

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

Acronym: NICOLHON

Important dates

Study start
2026
Primary completion
2028
Study completion
2028
First posted
Dec 2, 2025
Registry last updated
Dec 18, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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