Ocular Surface Metabolo-lipidomics in Lateral Amyotrophic Sclerosis

NCT04953286 | Completed

• 1 other identifier: DR210051
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 3

Brief Summary

Amyotrophic Lateral Sclerosis (ALS) is the most common neurodegenerative disease affecting the motor neuron. Currently, there is no diagnostic test and no examination that can predict the evolution of this pathology. The search for diagnostic and prognostic biomarkers is therefore essential for a better understanding of the pathophysiology of ALS, which remains poorly understood, and also for better clinical management. The ocular surface, made up of liquid elements, tears, and cells, is an accessible anatomical-physiological entity that has demonstrated its usefulness in the identification of biomarkers in neurodegenerative diseases such as Parkinson's or Alzheimer's. To date, no study has explored the ocular surface as a biomarker in ALS

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Amyotrophic Lateral Sclerosis; Biomarkers; Ocular Surface; Tear

Outcome Measures

Primary Outcomes (4)

• Metabolome profile in tears for the diagnosis and prognosis of ALS.

  Once the composition in metabolites (i.e. tear metabolome) is determined, statistical univariate and multivariate analyses will aim to determine if the tear metabolome can cluster ALS patients and controls and therefore can be used as a diagnosis biomarker

  Baseline

• Metabolome profile in intra-cellular contents for the diagnosis and prognosis of ALS.

  Once the composition in metabolites in conjunctival cells is determined, statistical univariate and multivariate analyses will aim to determine if the tear metabome can cluster ALS patients and controls and therefore can be used as a diagnosis biomarker.

  Baseline

• Lipidome profile in tears for the diagnosis and prognosis of ALS.

  Once the composition in lipids (i.e. tear lipidome) is determined, statistical univariate and multivariate analyses will aim to determine if the tear lipidome can cluster ALS patients and controls and therefore can be used as a diagnosis biomarker

  Baseline

• Lipidome profile in intra-cellular contents for the diagnosis and prognosis of ALS.

  Once the composition in lipids in conjunctival cells is determined, statistical univariate and multivariate analyses will aim to determine if the tear lipidome can cluster ALS patients and controls and therefore can be used as a diagnosis biomarker.

  Baseline

Secondary Outcomes (2)

• Evolution of the ocular surface metabolites during ALS progression using ultra-high performance liquid chromatography coupled with mass spectrometry

  Baseline

• Evolution of the ocular surface lipids during ALS progression using ultra-high performance liquid chromatography coupled with mass spectrometry

  Baseline

Study Arms (2)

Case group

OTHER

The procedure, specific to the study, consists in taking samples of tears and cells at inclusion, 3 months after inclusion and 6 months after inclusion on patients with Amyotrophic Lateral Sclerosis

Other: Measure of visual acuity; Other: Interferometry; Other: Samples of basal tears; Other: Central corneal sensitivity; Other: Slit lamp examination and undilated fundus; Other: Conjunctival impression; Other: Evaluation of the corneal innervation

Control group

OTHER

The procedure, specific to the study, consists in taking samples of tears and cells at inclusion, 3 months after inclusion and 6 months after inclusion on patients without neurological disease

Other: Measure of visual acuity; Other: Interferometry; Other: Samples of basal tears; Other: Central corneal sensitivity; Other: Slit lamp examination and undilated fundus; Other: Conjunctival impression; Other: Evaluation of the corneal innervation

Interventions

Measure of visual acuity OTHER

ETDRS and Parinaud scale

Case group; Control group

Interferometry OTHER

Non-contact exam measuring N.I.B.U.T (Non-invasive break-up time), quantitative and qualitative evaluation of the meibomian glands and quantitative evaluation of the tear meniscus

Case group; Control group

Samples of basal tears OTHER

Collection of basal tears without instillation of anesthetic with a Schirmer strip for 5 minutes and by microcapillary

Case group; Control group

Central corneal sensitivity OTHER

Central corneal sensitivity using a Cochet-Bonnet esthesiometer (Luneau©)

Case group; Control group

Slit lamp examination and undilated fundus OTHER

Slit lamp examination and undilated fundus

Case group; Control group

Conjunctival impression OTHER

Conjunctival impression with anesthetic instillation

Case group; Control group

Evaluation of the corneal innervation OTHER

Contact corneal confocal microscopy

Case group; Control group

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient with clinically defined or probable primary ALS according to Airlie House criteria(1)
• Familial or sporadic form
• ≥18 years of age
• Patient affiliated with a social security plan
• Informed consent signed by the patient

You may not qualify if:

• Motor neuron disease mimicking ALS
• Pregnant or breastfeeding woman
• Treatment that may have a neuroprotective effect
• Any eye drops or treatments that may interfere with tear production
• Lens wearer
• Eye surgery ≤3 months
• Any ocular pathology other than ametropia, oculomotor disorder, amblyopia
• Any general pathology other than ALS with ocular repercussions
• Protective measure of guardianship or curators
• Control group selection criteria:
• No diagnosed neurological pathology
• ≥18 years of age
• Patient affiliated with a social security plan
• Informed consent signed by the participant
• Pregnant or breastfeeding woman

Sponsors & Collaborators

• University Hospital, Tours: lead

Study Sites (3)

Ophthalmology Department, University Hospital of Tours, France

Tours, 37000, France

Location

Neurology Department, University Hospital of Tours, France

Tours, 37044, France

Location

Centre d'Investigation Clinique_CIC 1415

Tours, France

Location

Related Publications (1)

• Khanna RK, Catanese S, Mortemousque G, Dupuy C, Lefevre A, Emond P, Beltran S, Gissot V, Pisella PJ, Blasco H, Corcia P. Metabolomics of basal tears in amyotrophic lateral sclerosis: A cross-sectional study. Ocul Surf. 2024 Oct;34:363-369. doi: 10.1016/j.jtos.2024.09.005. Epub 2024 Sep 28.

  PMID: 39349171 RESULT

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Lacerations

Interventions

Interferometry; Slit Lamp

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Investigative Techniques; Ophthalmoscopes; Diagnostic Equipment; Equipment and Supplies

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2021
• First Posted: July 7, 2021
• Study Start: September 17, 2021
• Primary Completion: September 30, 2023
• Study Completion: September 30, 2023
• Last Updated: December 22, 2025

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3)