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

NCT02880033 | Completed

• 2 other identifiers: 2010_292010-A01216-33
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• hydroxyl radical measured

  hydroxypethidine probe with Fluorescence-activated cell sorting

  12 months

Secondary Outcomes (4)

• adenosine triphosphate production measured by seahorse

  12 months

• oxygen consumption measured by seahorse

  12 months

• free reactive iron (ferrous iron)

  12 months

• lipid peroxidation measured by Fluorescence-activated cell sorting

  12 months

Study Arms (3)

Parkinson's disease

ACTIVE COMPARATOR

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

Drug: deferiprone; Drug: placebo

Amyotrophic lateral sclerosis

ACTIVE COMPARATOR

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

Drug: deferiprone; Drug: placebo

healthy age and sex matched controls

PLACEBO COMPARATOR

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

Drug: deferiprone; Drug: placebo

Interventions

deferiprone DRUG

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

Also known as: FERRIPROX

Amyotrophic lateral sclerosis; Parkinson's disease; healthy age and sex matched controls

placebo DRUG

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

Amyotrophic lateral sclerosis; Parkinson's disease; healthy age and sex matched controls

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Parkinson's disease according to Movement Disorders Society criteria
• Amyotrophic Lateral Sclerosis according to El escorial criteria
• Age and sex matched healthy controls

You may not qualify if:

• Severe comorbidities (cancer, other degenerative diseases, hemopathy, inflammatory diseases)

Sponsors & Collaborators

• University Hospital, Lille: lead

Study Sites (1)

Hôpital Roger Salengro, CHRU de Lille

Lille, France

Location

Related Publications (6)

• Devos D, Moreau C, Kyheng M, Garcon G, Rolland AS, Blasco H, Gele P, Timothee Lenglet T, Veyrat-Durebex C, Corcia P, Dutheil M, Bede P, Jeromin A, Oeckl P, Otto M, Meininger V, Danel-Brunaud V, Devedjian JC, Duce JA, Pradat PF. A ferroptosis-based panel of prognostic biomarkers for Amyotrophic Lateral Sclerosis. Sci Rep. 2019 Feb 27;9(1):2918. doi: 10.1038/s41598-019-39739-5.

  PMID: 30814647 RESULT

• Moreau C, Danel V, Devedjian JC, Grolez G, Timmerman K, Laloux C, Petrault M, Gouel F, Jonneaux A, Dutheil M, Lachaud C, Lopes R, Kuchcinski G, Auger F, Kyheng M, Duhamel A, Perez T, Pradat PF, Blasco H, Veyrat-Durebex C, Corcia P, Oeckl P, Otto M, Dupuis L, Garcon G, Defebvre L, Cabantchik ZI, Duce J, Bordet R, Devos D. Could Conservative Iron Chelation Lead to Neuroprotection in Amyotrophic Lateral Sclerosis? Antioxid Redox Signal. 2018 Sep 10;29(8):742-748. doi: 10.1089/ars.2017.7493. Epub 2018 Feb 8.

  PMID: 29287521 RESULT

• Gouel F, Do Van B, Chou ML, Jonneaux A, Moreau C, Bordet R, Burnouf T, Devedjian JC, Devos D. The protective effect of human platelet lysate in models of neurodegenerative disease: involvement of the Akt and MEK pathways. J Tissue Eng Regen Med. 2017 Nov;11(11):3236-3240. doi: 10.1002/term.2222. Epub 2016 Dec 12.

  PMID: 27943621 RESULT

• Do Van B, Gouel F, Jonneaux A, Timmerman K, Gele P, Petrault M, Bastide M, Laloux C, Moreau C, Bordet R, Devos D, Devedjian JC. Ferroptosis, a newly characterized form of cell death in Parkinson's disease that is regulated by PKC. Neurobiol Dis. 2016 Oct;94:169-78. doi: 10.1016/j.nbd.2016.05.011. Epub 2016 May 14.

  PMID: 27189756 RESULT

• Devos D, Moreau C, Devedjian JC, Kluza J, Petrault M, Laloux C, Jonneaux A, Ryckewaert G, Garcon G, Rouaix N, Duhamel A, Jissendi P, Dujardin K, Auger F, Ravasi L, Hopes L, Grolez G, Firdaus W, Sablonniere B, Strubi-Vuillaume I, Zahr N, Destee A, Corvol JC, Poltl D, Leist M, Rose C, Defebvre L, Marchetti P, Cabantchik ZI, Bordet R. Targeting chelatable iron as a therapeutic modality in Parkinson's disease. Antioxid Redox Signal. 2014 Jul 10;21(2):195-210. doi: 10.1089/ars.2013.5593. Epub 2014 Feb 6.

  PMID: 24251381 RESULT

• Moreau C, Gosset P, Kluza J, Brunaud-Danel V, Lassalle P, Marchetti P, Defebvre L, Destee A, Devos D. Deregulation of the hypoxia inducible factor-1alpha pathway in monocytes from sporadic amyotrophic lateral sclerosis patients. Neuroscience. 2011 Jan 13;172:110-7. doi: 10.1016/j.neuroscience.2010.10.040. Epub 2010 Oct 25.

  PMID: 20977930 RESULT

MeSH Terms

Conditions

Parkinson Disease; Amyotrophic Lateral Sclerosis; Iron Overload

Interventions

Deferiprone

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Spinal Cord Diseases; Motor Neuron Disease; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Iron Metabolism Disorders

Intervention Hierarchy (Ancestors)

Pyridones; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• David DEVOS, MD, PhD

  University Hospital, Lille

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2016
• First Posted: August 26, 2016
• Study Start: February 1, 2011
• Primary Completion: October 1, 2019
• Study Completion: March 1, 2020
• Last Updated: May 14, 2026

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)