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

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ClinicalTrials.gov Identifier: NCT02880033
Recruitment Status : Active, not recruiting
First Posted : August 26, 2016
Last Update Posted : April 26, 2018
Sponsor:
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Parkinson's Disease Amyotrophic Lateral Sclerosis Oxidative Stress Iron Overload Drug: deferiprone Drug: placebo Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Estimated 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 : February 2011
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019


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 Name: 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 Name: 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 Name: FERRIPROX

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




Primary Outcome Measures :
  1. hydroxyl radical measured [ Time Frame: 12 months ]
    hydroxypethidine probe with Fluorescence-activated cell sorting


Secondary Outcome Measures :
  1. adenosine triphosphate production measured by seahorse [ Time Frame: 12 months ]
    seahorse experimentation

  2. oxygen consumption measured by seahorse [ Time Frame: 12 months ]
    seahorse experimentation

  3. free reactive iron (ferrous iron) [ Time Frame: 12 months ]
    calceine assay

  4. lipid peroxidation measured by Fluorescence-activated cell sorting [ Time Frame: 12 months ]
    flow cytometry with bodipy probe



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02880033


Locations
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France
Hôpital Roger Salengro, CHRU de Lille
Lille, France
Sponsors and Collaborators
University Hospital, Lille
Investigators
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Principal Investigator: David DEVOS, MD, PhD University Hospital, Lille

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Responsible Party: University Hospital, Lille
ClinicalTrials.gov Identifier: NCT02880033     History of Changes
Other Study ID Numbers: 2010_29
2010-A01216-33 ( Other Identifier: ID-RCB number, ANSM )
First Posted: August 26, 2016    Key Record Dates
Last Update Posted: April 26, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by University Hospital, Lille:
Parkinson's disease
Amyotrophic lateral sclerosis
Peripheral blood mononuclear cells
ex vivo model for oxidative stress
iron metabolism and chelation

Additional relevant MeSH terms:
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Sclerosis
Parkinson Disease
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Iron Overload
Pathologic Processes
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Neuromuscular Diseases
Spinal Cord Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Iron Metabolism Disorders
Deferiprone
Iron Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action