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

Not Applicable

Completed

• Conditions: Oxidative Stress; Iron Overload; Parkinson's Disease; Amyotrophic Lateral Sclerosis
• Interventions: Drug: deferiprone; Drug: placebo

• Registration Number: NCT02880033
• Lead Sponsor: University Hospital, Lille

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.

Study Timeline

• Study Start: 2011-02
• Study First Submitted: 2016-08-03
• Study First Submitted QC: 2016-08-22
• Study First Posted: 2016-08-26
• Primary Completion: 2019-10
• Status Verified: 2020-03
• Study Completion: 2020-03
• Last Update Submitted: 2020-03-25
• Last Update Posted: 2020-03-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 90

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
healthy age and sex matched controls	placebo	ex vivo analysis of lymphocytes from 30 healthy age and sex matched controls with deferiprone and placebo treatment
Amyotrophic lateral sclerosis	placebo	ex vivo analysis of lymphocytes from 30 patients with Amyotrophic lateral sclerosis with deferiprone and placebo treatment
Parkinson's disease	placebo	ex vivo analysis of lymphocytes from 30 patients with Parkinson's disease with deferiprone and placebo treatment
Parkinson's disease	deferiprone	ex vivo analysis of lymphocytes from 30 patients with Parkinson's disease with deferiprone and placebo treatment
Amyotrophic lateral sclerosis	deferiprone	ex vivo analysis of lymphocytes from 30 patients with Amyotrophic lateral sclerosis with deferiprone and placebo treatment
healthy age and sex matched controls	deferiprone	ex vivo analysis of lymphocytes from 30 healthy age and sex matched controls with deferiprone and placebo treatment

Primary Outcome Measures

Name	Time	Method
hydroxyl radical measured	12 months	hydroxypethidine probe with Fluorescence-activated cell sorting

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Hôpital Roger Salengro, CHRU de Lille; 🇫🇷 Lille, France