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

University Hospital, Lille

Status: Completed

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

Treatments: Drug: placebo; Drug: deferiprone

Study type: Interventional

Funder types: Other

Identifiers

NCT02880033

2010_29

2010-A01216-33 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 90 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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90 participants in 3 patient groups, including a placebo group

Parkinson's disease

Active Comparator group

Description:

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

Treatment:

Drug: placebo

Drug: deferiprone

Amyotrophic lateral sclerosis

Active Comparator group

Description:

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

Treatment:

Drug: placebo

Drug: deferiprone

healthy age and sex matched controls

Placebo Comparator group

Description:

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

Treatment:

Drug: placebo

Drug: deferiprone