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

NCT06230562 | Unknown

• 1 other identifier: DR230136
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Amyotrophic Lateral Sclerosis

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (1)

• Provide a method for identifying TDP-43 in PBMC bly flow cytometry.

  At 6 month

Study Arms (2)

Case group

EXPERIMENTAL

Biological: Blood sample

Control group

ACTIVE COMPARATOR

Biological: Blood sample

Interventions

Blood sample BIOLOGICAL

The intervention is to take a blood sample every 6 months for 1 year which is not part of health routine care

Case 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:

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

Sponsors & Collaborators

• University Hospital, Tours: lead

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Blood Specimen Collection

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

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

Elodie Mousset

CONTACT

+33247474665; e.mousset@chu-tours.fr

Study Design

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

Study Record Dates

• First Submitted: January 9, 2024
• First Posted: January 30, 2024
• Study Start: February 1, 2024
• Primary Completion: August 1, 2025
• Study Completion: August 1, 2025
• Last Updated: January 30, 2024

Record last verified: 2023-01