Leber Hereditary Optic Neuropathy (LHON)Phase 1NICOLHONNCT07258667
Pilot Study of the Efficacy of Nicotinamide (Vitamin B3) in Leber's Hereditary Optic Neuropathy
A Phase 1 study testing Nicotinamide treatment in people with Leber Hereditary Optic Neuropathy (LHON) and Leber's Hereditary Optic Neuropathy (LHON), run by University Hospital, Angers at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Leber Hereditary Optic Neuropathy (LHON), Leber's Hereditary Optic Neuropathy (LHON), Mitochondrial Disease
- What is being tested?
- Nicotinamide treatment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteFrance
- Study dates
- Apr 2026to Apr 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
Show all 14Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site
Angers University Hospital
Angers, 49933
Pascal Reynier, Professor, 02 41 35 36 37, PaReynier@chu-angers.fr
About this study
Official title: 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.
- Conditions
- Leber Hereditary Optic Neuropathy (LHON), Leber's Hereditary Optic Neuropathy (LHON), Mitochondrial Disease, Optic Nerve Disease
- Being tested
- Nicotinamide treatment
- Medical subject headings
- Optic Atrophy, Hereditary, Leber, Mitochondrial Diseases, Optic Nerve Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nicotinamide treatmentDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Nicotinamide | Experimental | Not described Receives: Drug: Nicotinamide treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 12 months
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.
Measured: inclusion, 3 months, 6 months, 9 months and 12 months
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.
Measured: inclusion, 3 months, 6 months, 9 months and 12 months
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
Measured: inclusion, 3 months, 6 months, 9 months and 12 months
The effectiveness of treatment on the evolution of the appearance of visual field
By the Goldman-type manual
Measured: inclusion, 3 months, 6 months, 9 months and 12 months
The effectiveness of treatment on the evolution of optic nerve fiber layer (RNFL) thickness
Measurement by optical coherence tomography (OCT)
Measured: inclusion, 3 months, 6 months, 9 months and 12 months
The effectiveness of treatment on the evolution of retinal ganglion cell complex (GCC)
Measurement by optical coherence tomography (OCT)
Measured: inclusion, 3 months, 6 months, 9 months and 12 months
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.
Measured: inclusion and 12 months
Biological efficacy of treatment
Nicotinamide levels in patients' blood
Measured: 3 and 12 months
Treatment tolerance on Hepatic toxicity
Transaminase levels
Measured: Inclusion, 3 months, 6 months, 9 months, 12 months
Treatment tolerance in the macula
Measurement by optical coherence tomography
Measured: Inclusion, 3 months, 6 months, 9 months, 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2025
- Study startApr 2026 (estimated)
- Primary completionApr 2028 (estimated)
- Study completionApr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leber Hereditary Optic Neuropathy (LHON)Studies of the same condition, open and under way.
- More trials run by University Hospital, AngersThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Angers
- Sponsor type
- Other government
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07258667
- Sponsor's protocol ID
- 49RC25_0169
- Other IDs
- 2025-524343-13-00, 2025
- Acronym
- NICOLHON
- Status last verified
- Dec 2025
- First submitted
- 20 Nov 2025
- Last updated
- 18 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NICOLHON - Pilot Study of the Efficacy of Nicotinamide (Vitamin B3) in Leber's Hereditary Optic Neuropathy
- ClinicalTrials.gov ID
- NCT07258667
- Acronym / sponsor ID
- NICOLHON / 49RC25_0169
- Conditions
- Leber Hereditary Optic Neuropathy (LHON), Leber's Hereditary Optic Neuropathy (LHON), Mitochondrial Disease, Optic Nerve Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 13 participants (estimated)
- Lead sponsor
- University Hospital, AngersOther government
- Study start
- Apr 2026 (estimated)
- Primary completion
- Apr 2028 (estimated)
- Study completion
- Apr 2028 (estimated)
- First posted
- 2 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nicotinamide | Experimental | Drug: Nicotinamide treatment |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (14 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nicotinamide treatmentAll 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. | Drug | Nicotinamide |
Primary outcome
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.
11 secondary outcomes
The effectiveness of treatment on the progression of corrected distance visual acuity
Time frame: 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
The effectiveness of treatment on the evolution of corrected near visual acuity
Time frame: inclusion, 3 months, 6 months, 9 months and 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 effectiveness of treatment on the evolution of the appearance of visual field
Time frame: 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
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
The effectiveness of treatment on the evolution of Patients' quality of life
Time frame: inclusion and 12 months
Biological efficacy of treatment
Time frame: 3 and 12 months
Treatment tolerance on Hepatic toxicity
Time frame: 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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2025.
- Individual participant dataSharing planned: 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nicotinamide treatment in people with Leber Hereditary Optic Neuropathy (LHON) and Leber's Hereditary Optic Neuropathy (LHON), run by University Hospital, Angers at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 18 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Pacal Reynier, Professor (0241355542, PaReynier@chu-angers.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2025.