Clinical trial NCT02880033: Oxidative Stress and Apoptosis of Energy Metabolism by Deferiprone From the Circulating Lymphocytes
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Parkinson's Disease
Amyotrophic Lateral Sclerosis
Oxidative Stress
Iron Overload
Keywords: Parkinson's disease
Amyotrophic lateral sclerosis
Peripheral blood mononuclear cells
ex vivo model for oxidative stress
iron metabolism and chelation
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
First posted: 2016-08-26
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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)

Primary outcomes:
measure: hydroxyl radical measured
timeFrame: 12 months
Secondary outcomes:
measure: adenosine triphosphate production measured by seahorse
timeFrame: 12 months
measure: oxygen consumption measured by seahorse
timeFrame: 12 months
measure: free reactive iron (ferrous iron)
timeFrame: 12 months
measure: lipid peroxidation measured by Fluorescence-activated cell sorting
timeFrame: 12 months
Other outcomes:
Locations:
city: Lille
country: France
facility: Hôpital Roger Salengro, CHRU de Lille
Study officials:
affiliation: University Hospital, Lille
name: David DEVOS, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: