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

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

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.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease; Amyotrophic Lateral Sclerosis; Iron Overload; Oxidative Stress
• Intervention / Treatment: Drug: deferiprone; Drug: placebo

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 Type: Interventional
• Enrollment (Actual): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Lille, France
    • Hopital Roger Salengro, CHRU de Lille

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
hydroxyl radical measured	hydroxypethidine probe with Fluorescence-activated cell sorting	12 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University Hospital, Lille

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (ACTUAL): October 1, 2019
• Study Completion (ACTUAL): March 1, 2020

Study Registration Dates

• First Submitted: August 3, 2016
• First Submitted That Met QC Criteria: August 22, 2016
• First Posted (ESTIMATE): August 26, 2016

Study Record Updates

• Last Update Posted (ACTUAL): March 27, 2020
• Last Update Submitted That Met QC Criteria: March 25, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Amyotrophic lateral sclerosis; Parkinson's disease; Peripheral blood mononuclear cells; ex vivo model for oxidative stress; iron metabolism and chelation
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Iron Metabolism Disorders; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Parkinson Disease; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Iron Overload; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Deferiprone
• Other Study ID Numbers: 2010_29; 2010-A01216-33 (OTHER: ID-RCB number, ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO