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

December 11, 2025 updated by: University Hospital, Angers

NICOLHON - 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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
13

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • France
      • Angers, France, 49933
        • Angers University Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Nicotinamide
Drug: 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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
inclusion, 3 months, 6 months, 9 months, and 12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
12 months
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
inclusion, 3 months, 6 months, 9 months and 12 months
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
inclusion, 3 months, 6 months, 9 months and 12 months
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)
inclusion, 3 months, 6 months, 9 months and 12 months
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)
inclusion, 3 months, 6 months, 9 months and 12 months
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.
inclusion and 12 months
Biological efficacy of treatment
Time Frame: 3 and 12 months
Nicotinamide levels in patients' blood
3 and 12 months
Treatment tolerance on Hepatic toxicity
Time Frame: Inclusion, 3 months, 6 months, 9 months, 12 months
Transaminase levels
Inclusion, 3 months, 6 months, 9 months, 12 months
Treatment tolerance in the macula
Time Frame: Inclusion, 3 months, 6 months, 9 months, 12 months
Measurement by optical coherence tomography
Inclusion, 3 months, 6 months, 9 months, 12 months
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.
inclusion, 3 months, 6 months, 9 months and 12 months
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.
inclusion, 3 months, 6 months, 9 months and 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital, Angers

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 20, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 20, 2025

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 2, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 18, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 11, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 49RC25_0169
  • 2025-524343-13-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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

IPD Sharing Time Frame

The data will be shared after signing a negotiated data transfer agreement ( data access agreement), for the duration specified in the agreement

IPD Sharing Access Criteria

The data will be made available via secure transfer (sharing platform approved by the university hospital: BlueFiles or Oodrive).

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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