NICOPA1-TOL: Tolerance and Efficacy Nicotinamide (Vitamin B3) in Dominant Optic Atrophy OPA1

Sponsor

University Hospital, Angers (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06007391

Collaborator

(none)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Dominant Optic Atrophy (hereafter known as DOA) is a neurodegenerative pathology of the optic nerve inducing progressive loss of central visual field and visual acuity. There is currently no proven treatment for this disease. The metabolomics work of Pascal Reynier's team revealed a specific metabolomic signature of DOA in the plasma of patients. This metabolomic signature revealed a relative deficiency in nicotinamide compared to a control population, a vitamin compound (vitamin B3) known to be neuroprotective for the optic nerve and mitochondria. Note that the investigator have also identified this nicotinamide deficiency in primary open-angle glaucoma and Leber's hereditary optic neuropathy, the other most common cause of hereditary optic neuropathy, these three optic nerve conditions sharing a common pathophysiological mechanism of mitochondrial deficit. In addition, an American team demonstrated the high neuroprotective power on the optic nerve of nicotinamide in a mouse model of glaucoma. These arguments converge towards the potential therapeutic interest of this vitamin in degenerative pathologies of the optic nerve. This is encouraged by the fact that two randomized clinical trials have confirmed a benefit of nicotinamide in glaucoma. The objective of this pilot study is to test the tolerance and efficacy of nicotinamide in DOA and DOA+ patients.

Condition or Disease	Intervention/Treatment	Phase
Nicotinamide Adverse Reaction	Drug: Nicotinamide	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

25 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Pilot Study of Tolerance and Efficacy Nicotinamide (Vitamin B3) in Dominant Optic Atrophy OPA1

Anticipated Study Start Date :

Sep 1, 2023

Anticipated Primary Completion Date :

Mar 1, 2025

Anticipated Study Completion Date :

Sep 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: nicotinamide	Drug: Nicotinamide nicotinamide 3g per day

Arm

Intervention/Treatment

Experimental: nicotinamide

Drug: Nicotinamide

nicotinamide 3g per day

Outcome Measures

Primary Outcome Measures

Number of patient with neurologic or ophtalmological adverse event [at 6 months]
photopic negative response PhNR, optical coherence tomography

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult patients
Patients with DOA or DOA+ due to a heterozygous pathogenic variant in the OPA1 gene
Naïve patients (> 3 months) in terms of taking nicotinamide
Patients able to take oral medication and comply with specific study procedures
Patients affiliated or beneficiaries of a social security scheme
Signature of voluntary, free and informed consent to participate in the study

Exclusion Criteria:

Asymptomatic patients (= healthy carriers of an OPA1 mutation but not having developed optic neuropathy)
Patients with another associated severe ophthalmological pathology (advanced glaucoma, retinal pathology, etc.)
Patients treated with Idebenone
Patients with a level of transaminase(s) (ASAT and/or ALAT) twice higher than the high normal value.
Pregnant, breastfeeding or parturient women
Patients with a contraindication to nicotinamide
Persons deprived of liberty by administrative or judicial decision
Patients subject to a legal protection measure
Persons undergoing psychiatric treatment under duress
Persons unable to express their consent