Ocular Surface Metabolo-lipidomics in Lateral Amyotrophic Sclerosis

Amyotrophic Lateral Sclerosis Clinical Trial

— LARMOMIQUE  

Official title:

Tear Fluid and Ocular Surface Metabolomics and Lipidomics in Lateral Amyotrophic Sclerosis: a Prospective Comparative Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04953286
• Other study ID #: DR210051
• Status: Completed
• Phase: N/A
• Start date: September 17, 2021
• Est. completion date: September 30, 2023

Study information

• Verified date: November 2023
• Source: University Hospital, Tours
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: September 30, 2023
• Est. primary completion date: September 30, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Case group selection criteria :

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

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Other:
• Measure of visual acuity
ETDRS and Parinaud scale
• Interferometry
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
• Samples of basal tears
Collection of basal tears without instillation of anesthetic with a Schirmer strip for 5 minutes and by microcapillary
• Central corneal sensitivity
Central corneal sensitivity using a Cochet-Bonnet esthesiometer (Luneau©)
• Slit lamp examination and undilated fundus
Slit lamp examination and undilated fundus
• Conjunctival impression
Conjunctival impression with anesthetic instillation
• Evaluation of the corneal innervation
Contact corneal confocal microscopy

Locations

Country	Name	City	State
France	Centre d'Investigation Clinique_CIC 1415	Tours
France	Neurology Department, University Hospital of Tours, France	Tours
France	Ophthalmology Department, University Hospital of Tours, France	Tours

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Tours

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	Evolution of the ocular surface metabolites during ALS progression using ultra-high performance liquid chromatography coupled with mass spectrometry	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).	Baseline
Secondary	Evolution of the ocular surface lipids during ALS progression using ultra-high performance liquid chromatography coupled with mass spectrometry	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).	Baseline