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

Not Applicable

Not yet recruiting

• Conditions: Amyotrophic Lateral Sclerosis
• Interventions: Biological: Blood sample

• Registration Number: NCT06230562
• Lead Sponsor: University Hospital, Tours

Brief 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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2023-01
• Study First Submitted: 2024-01-09
• Study First Submitted QC: 2024-01-19
• Last Update Submitted: 2024-01-19
• Study First Posted: 2024-01-30
• Last Update Posted: 2024-01-30
• Study Start: 2024-02
• Primary Completion: 2025-08
• Study Completion: 2025-08

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 60

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Case group	Blood sample	-
Control group	Blood sample	-

Primary Outcome Measures

Name	Time	Method
Presence of TDP-43 aggregates in PBMC	Evolution between baseline and 6 month	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.
PBMC accompanied by a protein expression profile under Nrf-2 control	Evolution between baseline and 6 month	From blood samples, RNA will be extracted from PBMCs and expression of Nrf-2 target genes will be analyzed by flow cytometry.

Secondary Outcome Measures

Name	Time	Method
Provide a method for identifying TDP-43 in PBMC bly flow cytometry.	At 6 month	From blood samples, use of antibody fragments that recognize TDP-43 in the cell cytoplasm.