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Not yet recruitingNCT07258667NICOLHONUpdated Dec 18, 2025

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

A Phase 1 interventional study of Nicotinamide treatment in Leber Hereditary Optic Neuropathy (LHON), Leber's Hereditary Optic Neuropathy (LHON) and Mitochondrial Disease, sponsored by University Hospital, Angers. Not yet recruiting at 1 site in France. Open to participants aged 16 Years and older. Per ClinicalTrials.gov, last updated 2025-12-18.

Sponsored by University Hospital, Angers · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
13
Allocation
Not applicable
Ages
16 Years and older
Sex
All
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Study 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.

02

Conditions studied

  • Leber Hereditary Optic Neuropathy (LHON)
  • Leber's Hereditary Optic Neuropathy (LHON)
  • Mitochondrial Disease
  • Optic Nerve Disease
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In context

Optic Atrophy, Hereditary, Leber

44 studies on the registry are indexed under Optic Atrophy, Hereditary, Leber; 9 are open to participants now.

This study's planned enrollment of 13 is below the median of 36 across 31 interventional studies indexed under Optic Atrophy, Hereditary, Leber.

Browse Optic Atrophy, Hereditary, Leber studies →

Lead sponsor

University Hospital, Angers is the lead sponsor of 478 studies on the registry; 120 are open to participants now.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
16 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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 (or parental consent for minors; assent for minors when applicable).

Exclusion criteria

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 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 .
  • Participation in another interventional study affecting LHON management.
  • Any condition that, in the investigator's judgment, could compromise patient safety or study integrity.
Terms in these criteria, in plain language(2)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
13 participants (estimated)

Study arms

  • Experimental
    Nicotinamide

    Drug: Nicotinamide treatment

Interventions

  • DrugNicotinamide 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.

06

What researchers measure

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.

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

Secondary outcomes

  1. 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

  2. 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.

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

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

    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.

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

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

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

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

  5. The effectiveness of treatment on the evolution of the appearance of visual field

    By the Goldman-type manual

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

  6. The effectiveness of treatment on the evolution of optic nerve fiber layer (RNFL) thickness

    Measurement by optical coherence tomography (OCT)

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

  7. The effectiveness of treatment on the evolution of retinal ganglion cell complex (GCC)

    Measurement by optical coherence tomography (OCT)

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

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

    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.

    Time frame: inclusion and 12 months

  9. Biological efficacy of treatment

    Nicotinamide levels in patients' blood

    Time frame: 3 and 12 months

  10. Treatment tolerance on Hepatic toxicity

    Transaminase levels

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

  11. Treatment tolerance in the macula

    Measurement by optical coherence tomography

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

07

Study locations

1 site
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References and documents

Individual participant data

Plan to share: Yes — Data will be shared upon reasonable request. Only de-identified data will be shared. Any data collected during the study may be shared. The protocol will be shared initially. Other documents may be shared at a later date upon request (e.g., the CRF to allow a collaborator to select the data they wish to access). The recipients of the data will be researchers. The data will be available for any purpose deemed relevant by the study investigator, based on a protocol provided by the requester, after verification of the obtaining of regulatory approvals, including the favorable opinion of an ethics committee. Supporting information

Supporting information: 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).

No publications or documents are linked to this record.

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 18, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT07258667
Responsible party
Sponsor
First posted
Dec 2, 2025
Start date
Apr 2026 (estimated)
Primary completion
Apr 2028 (estimated)
Completion
Apr 2028 (estimated)
Last update
Dec 18, 2025

Study contacts

Pacal Reynier, Professor
Contact
PaReynier@chu-angers.fr
0241355542

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is not yet recruiting, as verified in Dec 2025. You cannot join it, but the record below documents what was studied.

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