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

Sponsor

University Hospital, Lille (Other)

Overall Status

Completed

CT.gov ID

NCT02880033

Collaborator

(none)

Enrollment

Location

Arms

108.9

Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Parkinson's Disease Amyotrophic Lateral Sclerosis Oxidative Stress Iron Overload	Drug: deferiprone Drug: placebo	N/A

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

90 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Modulation of Oxidative Stress and Apoptosis of Energy Metabolism by Deferiprone From the Circulating Lymphocytes of Patients With Parkinson's Disease or Amyotrophic Lateral Sclerosis

Study Start Date :

Feb 1, 2011

Actual Primary Completion Date :

Oct 1, 2019

Actual Study Completion Date :

Mar 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Parkinson's disease ex vivo analysis of lymphocytes from 30 patients with Parkinson's disease with deferiprone and placebo treatment	Drug: deferiprone to test the action of deferiprone on lymphocytes from patients and controls ex vivo Other Names: FERRIPROX Drug: placebo to control the action of placebo on lymphocytes from patients and controls ex vivo
Active Comparator: Amyotrophic lateral sclerosis ex vivo analysis of lymphocytes from 30 patients with Amyotrophic lateral sclerosis with deferiprone and placebo treatment	Drug: deferiprone to test the action of deferiprone on lymphocytes from patients and controls ex vivo Other Names: FERRIPROX Drug: placebo to control the action of placebo on lymphocytes from patients and controls ex vivo
Placebo Comparator: healthy age and sex matched controls ex vivo analysis of lymphocytes from 30 healthy age and sex matched controls with deferiprone and placebo treatment	Drug: deferiprone to test the action of deferiprone on lymphocytes from patients and controls ex vivo Other Names: FERRIPROX Drug: placebo to control the action of placebo on lymphocytes from patients and controls ex vivo

Arm

Intervention/Treatment

Active Comparator: Parkinson's disease

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

Drug: deferiprone

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

Other Names:

FERRIPROX

Drug: placebo

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

Active Comparator: Amyotrophic lateral sclerosis

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

Drug: deferiprone

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

Other Names:

FERRIPROX

Drug: placebo

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

Placebo Comparator: healthy age and sex matched controls

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

Drug: deferiprone

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

Other Names:

FERRIPROX

Drug: placebo

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

Outcome Measures

Primary Outcome Measures

hydroxyl radical measured [12 months]
hydroxypethidine probe with Fluorescence-activated cell sorting

Secondary Outcome Measures

adenosine triphosphate production measured by seahorse [12 months]
seahorse experimentation
oxygen consumption measured by seahorse [12 months]
seahorse experimentation
free reactive iron (ferrous iron) [12 months]
calceine assay
lipid peroxidation measured by Fluorescence-activated cell sorting [12 months]
flow cytometry with bodipy probe