Metabolomics Analysis According to the Retinal Nerve Fiber Layer in Patients With NOHL Mutations (MétabOCT) (MétabOCT)

Metabolomics Analysis According to the Thickness of the Retinal Nerve Fiber Layer in Patients With NOHL Mutations

Leber hereditary optic neuropathy (LHON), due to mitochondrial DNA (mtDNA) mutations, is responsible for profound visual impairment. However, there is evidence that optic nerve damage begins before vision declines. There is no biomarker to determine when optic nerve damage begins before visual acuity decline occurs.

We hope that the analysis of metabolomics will reveal specific metabolomic profiles and different vitamin B3 and B9 levels depending on whether there are OCT signs of optic nerve damage in healthy patients with mtDNA mutations suggestive of LHON (11778, 3460 or 14484). The existence of an increase in the thickness of the optic fiber layer, whose normal values are well established, constitutes such a sign in favor of optic nerve damage.

Study Overview

• Status: Recruiting
• Conditions: Leber Hereditary Optic Neuropathy; Healthy Subjects
• Intervention / Treatment: Diagnostic test: Optical coherent tomography

Detailed Description

The primary objective is to determine the metabolomic profile of healthy patients carrying an mtDNA mutation suggestive of NOHL (11778, 3460 or 14484) with or without increased thickness of the optic fiber layer in OCT.

Given the difference in the prevalence of NOHL in men and women, with a sex ratio of 7 men to 3 women, this primary objective will be evaluated separately in these 2 groups of people.

Secondary objectives include Determination of the cellular metabolomic profile of healthy patients carrying an mtDNA mutation suggestive of NOHL (11778, 3460 or 14484) with or without increased thickness of the optic fiber layer in OCT.

Determination of the metabolomic profile in tears of healthy with an mtDNA mutation suggestive of NOHL (11778, 3460 or 14484) with or without increased thickness of the optical fiber layer in OCT.

Comparison of the serum and cellular metabolomic profile of healthy with an mtDNA mutation suggestive of NOHL (11778, 3460 or 14484) according to the existence or not of an increase in thickness of the optical fiber layer in macular OCT and with a control population without mtDNA mutation; Determination of a different clinical and paraclinical (OCT) evolution according to the metabolomic profiles.

Determination of vitamin B3 and B9 levels of healthy with an mtDNA mutation suggestive of NOHL (11778, 3460 or 14484) according to the existence or not of an increase in the thickness of the optical fiber layer in macular OCT and with a control population without mtDNA mutation.

For the reasons mentioned above, the secondary objectives will be studied separately in men and women with the constitution of 2 groups of patients.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: christophe Orssaud, MD; Phone Number: 33 +156093466; Email: christophe.orssaud@aphp.fr
• Study Contact Backup: Name: Pascal Reynier, MD PhD; Email: PaReynier@chu-angers.fr

Study Locations

• France
  • Paris
    • Paris, Paris, France, 75015
      • Recruiting
      • HEGP
      • Contact: Christophe ORSSAUD, MD; Phone Number: 33 1 56 09 34 98; Email: christophe.orssaud@aphp.fr
      • Contact: Dominique Bremond Gignac, MD PhD; Phone Number: 33 1 44 49 45 02; Email: dominique.bremond@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patient carrying an mtDNA mutation suggestive of NOHL (11778, 3460 or 14484) with normal visual acuity and who has never had optic neuropathy, or Patient not carrying an mtDNA mutation suggestive of NOHL (11778, 3460 or 14484) with normal visual acuity and who has never had optic neuropathy;
• Patient agreeing to undergo an OCT;
• Patient agreeing to sign the informed consent;
• Patient affiliated to French social protection (Primary Health Insurance Fund, CMU, etc.) or European social protection.

Exclusion Criteria:

• Patient with or having had optic neuropathy regardless of its etiology
• Patient with glaucoma regardless of its etiology;
• Patient not wanting to undergo OCT;
• Patient not wanting to sign the informed consent;
• Patient not affiliated with French social protection (Primary Health Insurance Fund, CMU, etc.) or European.
• Patients less than 18 years old or over 60 years old
• Pregnant patient

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Two arms will be constituted according to gender and crossed according to OCT data; Considering the difference in NOHL prevalence in men and women, with a sex ratio of 7 men to 3 women, the metabolomic analysis data will be analyzed according to gender and OCT data.	Diagnostic test: Optical coherent tomography; We compare the metabolomics profile of healthy patients based on the OCT appearance of the optic disc and RNFL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolomic profile of healthy patients carrying an mtDNA mutation suggestive of NOHL (11778, 3460 or 14484) with or without increased thickness of the optic fiber layer in OCT	Results of the metabolomics analysis in the different groups established according to the appearance of the OCT and gender in healthy patients carrying mtDNA mutations suggestive of LHON (11778, 3460 or 14484).	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolomic profile in tears of healthy patients carrying an mtDNA mutation suggestive of NOHL (11778, 3460 or 14484) with or without increased thickness of the optic fiber layer in OCT.	Results of the metabolome established on tears in the different groups established according to the appearance of the OCT and the gender in healthy patients carrying mtDNA mutation evocative of NOHL (11778, 3460 or 14484).	one year
Cellular metabolomic profile of healthy patients carrying an mtDNA mutation suggestive of NOHL (11778, 3460 or 14484) with or without increased thickness of the optic fiber layer in OCT.	Results of the cellular metabolome established on leukocytes in the different groups established according to the appearance of the OCT and the gender in healthy patients carrying mtDNA mutation evocative of NOHL (11778, 3460 or 14484).	one day
To assess a visual acuity evolution depending on the metabolomic profiles.	Monitoring of the clinical evolution of visual acuity for one year in the different groups established according to the OCT appearance and gender in healthy patients carrying mtDNA mutations suggestive of NOHL (11778, 3460 or 14484). comparison with metabolomic profiles.	one year
To assess a different OCT evolution depending on the metabolomic profiles.	Monitoring of the evolution of visual acuity and OCT data for one year in the different groups established according to the OCT appearance and gender in healthy patients carrying mtDNA mutations suggestive of NOHL (11778, 3460 or 14484). comparison with metabolomic profiles.	one year
Comparison of vitamin B3 and B9 levels in healthy patients with an mtDNA mutation suggestive of NOHL (11778, 3460 or 14484) according to macular OCT data and with a control population without mtDNA mutation.	Measurement of blood levels of vitamins B3 and B9 in different groups established according to OCT appearance and gender in healthy patients carrying mtDNA mutations suggestive of NOHL (11778, 3460 or 14484).	one year

Collaborators and Investigators

• Sponsor: Hôpital Necker-Enfants Malades
• Investigators: Principal Investigator: Christophe Orssaud, MD, Hôpital Necker

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2023
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: October 30, 2024
• First Submitted That Met QC Criteria: November 7, 2024
• First Posted (Actual): November 12, 2024

Study Record Updates

• Last Update Posted (Actual): November 18, 2025
• Last Update Submitted That Met QC Criteria: November 15, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: OCT; Metabolomics analysis; mtDNA mutation; Leber hereditary optic neuropathy
• Additional Relevant MeSH Terms: Nervous System Diseases; 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; Optic Atrophy; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Optic Atrophy, Hereditary, Leber
• Other Study ID Numbers: MétabOCT-022022; 2022-A00537-36 (Other Identifier: ID-RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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