Pilot study of the efficacy of nicotinamide (vitamin B3) in Leber's hereditary optic neuropathy - NICOLHON

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire D'Angers

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11], Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2026-03-03

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The primary objective is to evaluate the efficacy of administering 2 grams per day of nicotinamide for one year in patients who have developed NOHL due to the m.11778G>A or m.3460G>A mutation within the last 18 months

Secondary objectives 10

1. The effectiveness of treatment on the progression of corrected distance visual acuity
2. The effectiveness of treatment on the progression of corrected distance visual acuity
3. The effectiveness of treatment on the progression of corrected near visual acuity
4. The effectiveness of treatment on the progression of campimetric deficits
5. The effectiveness of treatment on the evolution of the appearance of the Goldman-type manual visual field
6. The effectiveness of treatment on changes in the thickness of the retinal nerve fiber layer (RNFL) and the thickness of the retinal ganglion cell complex (GCC)
7. The effectiveness of treatment on changes in patients' quality of life
8. The biological effectiveness of the treatment
9. Tolerance of treatment liver toxicity
10. Tolerance of treatment for macular changes

Conditions and MedDRA coding

Leber's Hereditary Optic Neuropathy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Patients aged 16 years and older
2. Patients with NOHL due to a m.11778G>A or m.3460G>A mutation in mitochondrial DNA
3. Patients who are naïve (> 3 months) to nicotinamide treatment
4. Patients able to take oral medication and comply with specific study procedures
5. Patients affiliated with or beneficiaries of a social security system
6. Patients who have signed an informed consent form or parental consent form (or guardianship holders) for minors

Exclusion criteria 14

1. Asymptomatic patients (= healthy carriers of a m.11778G>A or m.3460G>A mutation in mitochondrial DNA but who have not developed optic neuropathy)
2. Patients with symptomatic or asymptomatic LOHN caused by another mitochondrial DNA mutation or a nuclear DNA mutation
3. Patients with NOHL for more than 18 months
4. Patients taking idebenone or who have stopped treatment less than 3 months ago
5. Patients with another severe associated ophthalmological condition (advanced glaucoma, retinal disease, etc.)
6. Patients treated with gene therapy
7. Patients with transaminase (AST and/or ALT) levels twice the upper normal limit
8. Pregnant women, breastfeeding women, or women in labor
9. Patients with a contraindication to nicotinamide, an allergy or intolerance to lactose or galactose
10. Persons deprived of their liberty by administrative or judicial decision
11. Patients subject to legal protection measures
12. Persons undergoing compulsory psychiatric care
13. Individuals unable to express consent
14. Patients already included in an interventional study modifying the management of NOHL

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint will be the change in corrected distance visual acuity measured eye by eye using the ETDRS (Early Treatment Diabetic Retinopathy Study) scale over the entire follow-up period (inclusion, 3, 6, 9, and 12 months).

Secondary endpoints 10

1. corrected distance visual acuity measured eye by eye at 12 months using the ETDRS scale, taking the nadir (lowest visual acuity reached a few weeks after the onset of NOHL) as the reference value
2. corrected distance visual acuity measured eye by eye on a Monoyer scale
3. corrected near visual acuity measured eye by eye on a Parinaud scale
4. campimetric deficits based on the average and corrected average deviation measured in STAT 30 on an automated visual field
5. the appearance of the Goldman-type manual visual field
6. changes in the thickness of the retinal nerve fiber layer (RNFL) and the thickness of the retinal ganglion cell complex (GCC) measured by OCT (Optical Coherence Tomography)
7. Patients' quality of life assessed using the NEI VFQ 25 questionnaire
8. The biological efficacy of the treatment assessed by the evolution of nicotinamide in patients' blood at 3 and 12 months
9. Hepatic toxicity assessed by transaminase levels
10. Optical coherence tomography (OCT) changes in the macula

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire D'Angers

Sponsor organisation

Centre Hospitalier Universitaire D'Angers

Address

4 Rue Larrey

City

Angers

Postcode

49100

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire D'Angers

Contact name

Coordinating investigator

Public contact point

Organisation

Centre Hospitalier Universitaire D'Angers

Contact name

Promotion interne CHU

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 23 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications