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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Nicotinamide Adverse Reaction
• Intervention / Treatment: Drug: Nicotinamide

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• France
  • Angers, France
    • Angers University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patient with neurologic or ophtalmological adverse event	photopic negative response PhNR, optical coherence tomography	at 6 months

Collaborators and Investigators

• Sponsor: University Hospital, Angers

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: July 6, 2023
• First Submitted That Met QC Criteria: August 17, 2023
• First Posted (Actual): August 23, 2023

Study Record Updates

• Last Update Posted (Actual): April 1, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pathological Conditions, Anatomical; Genetic Diseases, Inborn; Metabolic Diseases; Eye Diseases; Neurodegenerative Diseases; Eye Diseases, Hereditary; Heredodegenerative Disorders, Nervous System; Optic Nerve Diseases; Cranial Nerve Diseases; Mitochondrial Diseases; Optic Atrophies, Hereditary; Atrophy; Optic Atrophy; Optic Atrophy, Autosomal Dominant; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Acids, Heterocyclic; Nicotinic Acids; Niacinamide
• Other Study ID Numbers: 49RC23_0195

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No