DIAGALS: Relation Between Tar DNA Binding Protein(TDP)-43 et Nrf-2 in ALS: a Track to Improve Diagnosis and Prognosis of the Disease

Amyotrophic Lateral Sclerosis Clinical Trial

— DIAGALS  

Official title:

DIAGALS: Relation Between TDP-43 et Nrf-2 in ALS: a Track to Improve Diagnosis and Prognosis of the Disease: Prospective, Bicentric, Non-randomized, Open-label Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06230562
• Other study ID #: DR230136
• Status: Not yet recruiting
• Phase: N/A
• Start date: February 2024
• Est. completion date: August 2025

Study information

• Verified date: January 2023
• Source: University Hospital, Tours
• Contact: Elodie Mousset
• Phone: +33247474665
• Email: e.mousset[@]chu-tours.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In response to oxidative stress, cells activate the Nrf-2 pathway, which induces translation of its target genes and corresponding proteins involved in the antioxidant response. This explains the interest in the Nrf-2 pathway in the pathophysiology of Amyotrophic lateral sclerosis (ALS), supported by the results of several studies and the modulatory effect of TDP-43 on the Nrf-2 pathway. Since both TDP-43 and Nrf-2 proteins are present in the peripheral blood mononuclear cells (PBMC) of ALS patients and may be correlated with disease progression, the investigators wish to explore their relationship and their application in the clinic as potential blood biomarkers for ALS.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: August 2025
• Est. primary completion date: August 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Patients group :

Inclusion Criteria:

• Men and women = 18 years old
• Person affiliated to a French social security scheme or equivalent
• ALS diagnosed according to El Escorial criteria
• Diagnosis of ALS < 6 months
• Onset of symptoms < 2 years
• Signed informed consent

Non-inclusion criteria :

• Pregnant or breast-feeding
• Treatment with oral or injectable anticoagulants, antiplatelet agents (EXCEPT aspirin at the maximum authorized dosage of 160 mg per day)
• Unbalanced diabetes
• Long-term corticosteroid therapy
• Persons deprived of their liberty by judicial or administrative decision; Persons under legal protection: guardianship or curators
• Genetic mutations associated with ALS Control group :

Inclusion criteria:

• Male or female volunteer aged 18 or over
• Person affiliated to a French social security scheme or equivalent
• Signed informed consent

Non-inclusion criteria :

• Pregnant or breast-feeding women
• Treatment with oral or injectable anticoagulants, antiplatelet agents (except aspirin at the maximum authorized dosage of 160 mg per day)
• Unbalanced diabetes
• Long-term corticosteroid therapy
• Neurological diseases
• Patient under legal protection (safeguard of justice, curators and guardianship), or in a situation of deprivation of liberty
• Genetic mutations associated with ALS

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease

Intervention

Biological:
• Blood sample
The intervention is to take a blood sample every 6 months for 1 year which is not part of health routine care
• Blood sample
The intervention is to take a blood sample at baseline.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Tours

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Presence of TDP-43 aggregates in PBMC	Peripheral blood samples from ALS patients and controls will be collected at inclusion and at follow-up visits for patients.; PBMC isolation and monocyte/lymphocyte enrichment will be performed using a Percoll gradient or magnetic bead separation.	Evolution between baseline and 6 month
Primary	PBMC accompanied by a protein expression profile under Nrf-2 control	From blood samples, RNA will be extracted from PBMCs and expression of Nrf-2 target genes will be analyzed by flow cytometry.	Evolution between baseline and 6 month
Secondary	Provide a method for identifying TDP-43 in PBMC bly flow cytometry.	From blood samples, use of antibody fragments that recognize TDP-43 in the cell cytoplasm.	At 6 month