Ocular Surface Metabolo-lipidomics in Lateral Amyotrophic Sclerosis

Not Applicable

Completed

• Conditions: Amyotrophic Lateral Sclerosis
• Interventions: 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

• Registration Number: NCT04953286
• Lead Sponsor: University Hospital, Tours

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-05-17
• Study First Submitted QC: 2021-07-06
• Study First Posted: 2021-07-07
• Study Start: 2021-09-17
• Primary Completion: 2023-09-30
• Study Completion: 2023-09-30
• Status Verified: 2023-11
• Last Update Submitted: 2023-12-04
• Last Update Posted: 2023-12-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 55

Inclusion Criteria

• 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

Exclusion Criteria

• 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:

Inclusion Criteria:

• No diagnosed neurological pathology
• ≥18 years of age
• Patient affiliated with a social security plan
• Informed consent signed by the participant

Exclusion Criteria:

• Pregnant or breastfeeding woman
• Treatment likely to have a neuroprotective effect
• Any eye drops or treatments that may interfere with tear production
• Lens wearer
• Eye surgery ≤3 months
• Any ocular pathology except ametropia, oculomotor disorder, amblyopia
• Any general pathology with ocular repercussions
• Protective measure of guardianship or curator

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control group	Interferometry	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
Control group	Samples of basal tears	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
Control group	Slit lamp examination and undilated fundus	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
Case group	Central corneal sensitivity	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
Case group	Interferometry	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
Case group	Samples of basal tears	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
Case group	Slit lamp examination and undilated fundus	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
Case group	Evaluation of the corneal innervation	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
Control group	Measure of visual acuity	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
Case group	Conjunctival impression	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
Control group	Conjunctival impression	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
Case group	Measure of visual acuity	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
Control group	Central corneal sensitivity	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
Control group	Evaluation of the corneal innervation	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

Primary Outcome Measures

Name	Time	Method
Metabolome profile in intra-cellular contents for the diagnosis and prognosis of ALS.	Baseline	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.
Metabolome profile in tears for the diagnosis and prognosis of ALS.	Baseline	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
Lipidome profile in tears for the diagnosis and prognosis of ALS.	Baseline	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
Lipidome profile in intra-cellular contents for the diagnosis and prognosis of ALS.	Baseline	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.

Secondary Outcome Measures

Name	Time	Method
Evolution of the ocular surface metabolites during ALS progression using ultra-high performance liquid chromatography coupled with mass spectrometry	Baseline	By carrying out a longitudinal analysis in ALS cases, the modification in tear and cells metabo-lipidome will be assessed at three time-points (at diagnosis, at month 3 and 6) and will correlated with bioclinical criteria of ALS progression (i.e. % of weight loss, % of slope of progression of the ALS-FRS-r score and % of decrease in forced vital capacity). This analysis will aim to search for analytes that can predict ALS progression (i.e. prognosis biomarker).
Evolution of the ocular surface lipids during ALS progression using ultra-high performance liquid chromatography coupled with mass spectrometry	Baseline	By carrying out a longitudinal analysis in ALS cases, the modification in tear and cells metabo-lipidome will be assessed at three time-points (at diagnosis, at month 3 and 6) and will correlated with bioclinical criteria of ALS progression (i.e. % of weight loss, % of slope of progression of the ALS-FRS-r score and % of decrease in forced vital capacity). This analysis will aim to search for analytes that can predict ALS progression (i.e. prognosis biomarker).

Trial Locations

Locations (3)

Ophthalmology Department, University Hospital of Tours, France; 🇫🇷 Tours, France

Centre d'Investigation Clinique_CIC 1415; 🇫🇷 Tours, France

Neurology Department, University Hospital of Tours, France; 🇫🇷 Tours, France