Oxidative Stress and Apoptosis of Energy Metabolism by Deferiprone From the Circulating Lymphocytes

NCT ID: NCT02880033

Last Updated: 2020-03-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-02-28
• Study Completion Date: 2020-03-31

Brief Summary

Peripheral blood mononuclear cells (PBMC) and platelets could be interesting ex vivo models to study brain diseases. Indeed, there is no access to neurons from patients. However, PBMC can exhibit different physiopathological mechanisms that are ubiquitous (i.e. oxidative stress, mitochondriopathy with energy metabolism, inflammation, protein folding, iron metabolism and programmed cell death ...). The platelets are pivotal in the healing system with large range of growth factors. A new therapeutic concept of conservative iron chelation with deferiprone for neuroprotection is under development.

The action of deferiprone on the different mechanisms and notably the oxidative stress are to obtain from a collection of PBMC and platelets from patient having Parkinson's disease and Amyotrophic lateral sclerosis and healthy controls to study ex vivo.

PBMC and platelets will be stored for future analyses.

Detailed Description

The study collection of PBMC and platelets from 30 patient having Parkinson's disease 30 patients having Amyotrophic lateral sclerosis and 30 healthy controls.

The collection will be performed either by cytapheresis for half of the patient and by collecting the whole blood for the other half.

PBMC and platelets will be stored at minus 80°C. PBMC of patients and controls are exposed ex vivo to different pathological condition (mainly Hydrogen peroxide, menadione, hypoxia...) with and without deferiprone to analyse whether the level of oxidative stress (Reactive Oxygen Species and notably hydroxyl radical with hydroxypethidine probe with flow cytometry) is reduced under deferiprone (primary criterion. Secondary analyses will concern the level of iron, the energy metabolism (aerobic versus anaerobic and the level of Adenosine triphosphate production), the type of cell death (apoptosis, autophagy and new programmed cell death: Ferroptosis) and inflammation. Finally, the level of growth factors and their effectiveness will be studied from platelets.

Conditions

Parkinson's Disease; Amyotrophic Lateral Sclerosis; Oxidative Stress; Iron Overload

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Parkinson's disease

ex vivo analysis of lymphocytes from 30 patients with Parkinson's disease with deferiprone and placebo treatment

Group Type: ACTIVE_COMPARATOR

deferiprone

Intervention Type: DRUG

to test the action of deferiprone on lymphocytes from patients and controls ex vivo

placebo

Intervention Type: DRUG

to control the action of placebo on lymphocytes from patients and controls ex vivo

Amyotrophic lateral sclerosis

ex vivo analysis of lymphocytes from 30 patients with Amyotrophic lateral sclerosis with deferiprone and placebo treatment

Group Type: ACTIVE_COMPARATOR

deferiprone

Intervention Type: DRUG

to test the action of deferiprone on lymphocytes from patients and controls ex vivo

placebo

Intervention Type: DRUG

to control the action of placebo on lymphocytes from patients and controls ex vivo

healthy age and sex matched controls

ex vivo analysis of lymphocytes from 30 healthy age and sex matched controls with deferiprone and placebo treatment

Group Type: PLACEBO_COMPARATOR

deferiprone

Intervention Type: DRUG

to test the action of deferiprone on lymphocytes from patients and controls ex vivo

placebo

Intervention Type: DRUG

to control the action of placebo on lymphocytes from patients and controls ex vivo

Interventions

deferiprone

to test the action of deferiprone on lymphocytes from patients and controls ex vivo

Intervention Type: DRUG

placebo

to control the action of placebo on lymphocytes from patients and controls ex vivo

Intervention Type: DRUG

Other Intervention Names

FERRIPROX

Eligibility Criteria

Inclusion Criteria

• Parkinson's disease according to Movement Disorders Society criteria
• Amyotrophic Lateral Sclerosis according to El escorial criteria
• Age and sex matched healthy controls

Exclusion Criteria

• Severe comorbidities (cancer, other degenerative diseases, hemopathy, inflammatory diseases)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Lille

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David DEVOS, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Lille

Locations

Hôpital Roger Salengro, CHRU de Lille

Lille, , France

Countries

France

Other Identifiers

2010-A01216-33

Identifier Type: OTHER

Identifier Source: secondary_id

2010_29

Identifier Type: -

Identifier Source: org_study_id