- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02655315
Conservative Iron Chelation as a Disease-modifying Strategy in Parkinson's Disease (FAIRPARKII)
November 4, 2022 updated by: University Hospital, Lille
Conservative Iron Chelation as a Disease-modifying Strategy in Parkinson's Disease. European Multicentre, Parallel-group, Placebo-controlled, Randomized Clinical Trial of Deferiprone"
This study evaluates the effect of iron chelation as a therapeutic strategy to slow the progression of Parkinson's disease.
Half of participants will receive the deferiprone to 15 mg / kg twice daily morning and evening (30mg / kg per day), while the other half will receive a placebo.
The treatment lasts nine months.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
This is the new concept of "conservative iron chelation".
We recently demonstrated (for the first time) the feasibility, efficacy and acceptability of the conservative iron chelation approach in pilot translational studies in Parkinson's disease with a prototype drug: deferiprone (1,2-dimethyl-3-hydroxypyridin-4-one) (in the FAIR-PARK-I project led by the applicant and funded by French Ministry of Health).
The only available blood-brain-barrier-permeable iron chelator deferiprone is approved for treating systemic iron overload in transfused patients with thalassemia.
Deferiprone has been on the European Union market since 1999, with a favourable risk/benefit balance at dose of 75 to 100 mg/kg/day.
The investigators shall adopt a repositioning strategy by using deferiprone at a lower dose of 30 mg/kg/day in this new indication for local iron overload in Parkinson's disease.
Deferiprone will be the first-in-class drug for this novel therapeutic strategy.
On the basis of the preclinical and clinical data from (FAIR-PARK-I), the present (FAIR-PARK-II) project should constitute a model for future cytoprotection strategies in neurodegenerative diseases; if deferiprone treatment is associated with significant slower disease progression, it would be the first non-dopaminergic drug to have a proven disease-modifying effect in Parkinson's disease.
Study Type
Interventional
Enrollment (Actual)
372
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Innsbruck, Austria
- Medizinische Universität Innsbruck
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Prague, Czechia
- Univerzita Karlova v Praze
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Praha, Czechia
- Charles University
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Bordeaux, France
- CHU Pellegrin
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Bron, France
- Hôpital Wertheimer
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Clermont-Ferrand, France
- Hôpital Montpied
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Lille, France
- Hôpital Salengro, CHRU
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Marseille, France
- CHU La Timone
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Paris, France
- AP-HP, Hôpital Pitié-Salpêtrière
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Strasbourg, France
- CHU de Strasbourg, Hôpital de Hautepierre
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Toulouse, France
- CHU Purpan
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Homburg, Germany
- University Hospital, Saarland University
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Kiel, Germany
- Christian-albrechts universität zu kiel
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Rostock, Germany
- Klinik und Poliklinik für Neurologie der Universitätsmedizin Rostock
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Amsterdam, Netherlands
- Acadamic central center, Amsterdam
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Nijmegen, Netherlands
- Radboud University Medical Center
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Coimbra, Portugal
- Centro Hospitalar e Universitário de Coimbra
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Guimarães, Portugal
- Centro Hospitalar do Alto Ave
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Lisbon, Portugal
- Centro Hospitalar Lisboa Norte
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Barcelona, Spain
- Hospital de la Santa Creu i Sant Pau
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Barcelona, Spain
- Hospital de Bellvitge
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Barcelona, Spain
- Hospital Clinic Universitari de Barcelona
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Cambridge, United Kingdom
- Cambridge university hospital
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Glasgow, United Kingdom
- University of Glasgow
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Newcastle, United Kingdom
- Newcastle University
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
No older than 78 years (Child, Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Adult patients
- Parkinson's disease diagnosed according United Kingdom Parkinson's disease Society Brain Bank Clinical Diagnostic Criteria and based on the presence of at least two of the three cardinal features of the disease (rest tremor, bradykinesia and rigidity). If rest tremor is not present, subjects must have unilateral onset of symptoms.
- Treatment-naïve, i.e. the best population for assessing a disease-modifying effect without the interaction of dopaminergic treatment (no dopaminergic agonists, L-dopa, anticholinergics, monoamine oxidase B inhibitors (e.g. rasagiline) or deep brain stimulation).
- Patients covered by a Health Insurance System in countries where required by law
- Written informed consent dated and signed prior to the beginning of any procedures related to the clinical trial
Exclusion Criteria:
- Disease duration greater than 18 months.
- Patients with high frequency of comorbidity or vital risks that may reasonably impair life expectancy
- Subject with handicap required dopaminergic treatment at the inclusion and therefore likely not to bear 9 months without symptomatic treatment
- Hoehn and Yahr stage 3 or more.
- Significant cognitive impairment (a Mini Mental State Examination score <24 or an equivalent impairment on a similar scale) or dementia diagnosed in accordance with the Movement Disorders Society criteria (Emre et al., 2007).
- Atypical or secondary parkinsonism (supranuclear palsy, multisystem atrophy, etc.) or anomalies on MRI suggestive of vascular involvement or significant cortical or subcortical atrophy (i.e. atypical for Parkinson's Disease).
- Progressing axis I psychiatric disorders (psychosis, hallucinations, substance addiction, bipolar disorder, or severe depression), in accordance with the Diagnostic and Statistical Manual of Mental Disorders.
- Subjects undergoing brain stimulation.
- Positive Human Immunodepression Virus serology.
- Hypersensitivity to deferiprone.
- Patients with agranulocytosis or with a history of agranulocytosis.
- Patients taking a treatment at risk of agranulocytosis (clozapine, Closaril®/Leponex®).
- Patients with anaemia (regardless of the latter's aetiology) or a history of another haematological disease. Haemochromatosis is not an exclusion criterion.
- Pregnant or breastfeeding women or women of childbearing potential not taking highly effective contraception.
- Kidney or liver failure.
- Other serious diseases.
- Inability to provide informed consent.
- Participation in another clinical trial with investigational medicinal product within 3 months prior to inclusion in the study
- Patient who has suffered mild or moderate depressive episode and isn't in remission and on a stable medication for at least 8 weeks
- Patient > 130k
Exclusion criteria for the biomarker study and the ancillary study (i) Magnetic Resonance Imaging:
- Subjects for whom Magnetic Resonance Imaging is contraindicated (metal objects in the body, severe claustrophobia, pacemaker, incompatible surgical material).
- Very severe rest tremor, which could induce Magnetic Resonance Imaging artefacts.
(ii) Lumbar puncture:
- Blood coagulation disorders, antiplatelet drugs or anticoagulants.
- Intracranial hypertension. (iii) Contraindications to nitrous oxide:
- Ventilation with Fraction of inspired Oxygen >50%, emphysema or pneumothorax
- Altered states of consciousness, non-cooperative patient (need to stop the nitrous oxide)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Active Comparator: DEFERIPRONE
Half of participants will receive the deferiprone (DFP) to 15 mg / kg twice daily morning and evening (30mg / kg per day).The treatment lasts nine months.
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15 mg / kg twice daily morning and evening (30mg / kg per day).The treatment lasts nine months.
Other Names:
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Placebo Comparator: PLACEBO
Half of participants will receive the placebo twice daily morning and evening.
The treatment lasts nine months.
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the placebo twice daily morning and evening.
The treatment lasts nine months
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Global effect (symptomatic and disease modifying effects) on motor and non motor handicap
Time Frame: at 36 weeks
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the change in the total Movement Disorders Society-Unified Parkinson Disease Rating Scale score between baseline and 36 weeks (i.e. the end of the placebo-controlled phase for analysis of both disease-modifying and symptomatic effects)
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at 36 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Disease-modifying effect on motor and non motor handicap
Time Frame: baseline, at 40 weeks
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It will be measured as the changes in the overall Movement Disorders Society-Unified Parkinson Disease Rating Scale score between baseline and week 40 (i.e. the end of the one-month post-treatment monitoring period), to analyse the disease-modifying effect without bias from the symptomatic effect of ongoing deferiprone treatment) on the study population
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baseline, at 40 weeks
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Effect of the motor symptoms
Time Frame: baseline, at 12, 36 and 40 weeks
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The effect of the motor symptoms will be analysed as the change in the subscale part III of the Movement Disorders Society-Unified Parkinson Disease Rating Scale score
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baseline, at 12, 36 and 40 weeks
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Quality of life and autonomy by PDQ-39 score
Time Frame: baseline, at 36 and 40 weeks
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It will be analyzed as the change in the Parkinson's Disease Quality of Life (PDQ-39, via a 39-item self-questionnaire)
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baseline, at 36 and 40 weeks
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Quality of life and autonomy by Clinical Global Impression score
Time Frame: baseline, at 36 and 40 weeks
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the Clinical Global Impression scored by the examiner and the patient
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baseline, at 36 and 40 weeks
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Health economics assessment
Time Frame: baseline, at 36 and 40 weeks
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will be performed via a specific questionnaire provides a simple descriptive profile and a single index value for health status
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baseline, at 36 and 40 weeks
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EQ-5D questionnaire
Time Frame: baseline, at 36 and 40 weeks
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the questionnaire provides a simple descriptive profile and a single index value for health status.
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baseline, at 36 and 40 weeks
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Safety criteria
Time Frame: 40 weeks
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All the safety concerns will be listed in a table with the number of patients, the type the severity and the time of occurrence for
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40 weeks
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Effect on overall cognitive status
Time Frame: baseline, at 12, 36 and 40 weeks
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Measured by the score in the Montreal Cognitive Assessment
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baseline, at 12, 36 and 40 weeks
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Effect on gait disorders
Time Frame: baseline, at 12, 36 and 40 weeks
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Measured by the Stand Walk Sit test
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baseline, at 12, 36 and 40 weeks
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Effect on daily living
Time Frame: baseline, at 12, 36 and 40 weeks
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The effect on daily living will be analysed as the change in the subscale part II (activities of daily living) of the Movement Disorders Society-Unified Parkinson Disease Rating Scale score
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baseline, at 12, 36 and 40 weeks
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Effect on non-motor symptoms
Time Frame: baseline, at 12, 36 and 40 weeks
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The effect on non motor symptoms will be analysed as the change in the subscale part I (cognition and behavior) of the Movement Disorders Society-Unified Parkinson Disease Rating Scale score
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baseline, at 12, 36 and 40 weeks
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Lack of occurrence of motor fluctuations
Time Frame: baseline, at 12, 36 and 40 weeks
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The lack of occurrence of motor fluctuations will be analysed on the subscale part IV of the Movement Disorders Society-Unified Parkinson Disease Rating Scale score
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baseline, at 12, 36 and 40 weeks
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Chair: David DEVOS, MD, PhD, University Hospital, Lille
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Mahoney-Sanchez L, Bouchaoui H, Ayton S, Devos D, Duce JA, Devedjian JC. Ferroptosis and its potential role in the physiopathology of Parkinson's Disease. Prog Neurobiol. 2021 Jan;196:101890. doi: 10.1016/j.pneurobio.2020.101890. Epub 2020 Jul 26.
- Moreau C, Duce JA, Rascol O, Devedjian JC, Berg D, Dexter D, Cabantchik ZI, Bush AI, Devos D; FAIRPARK-II study group. Iron as a therapeutic target for Parkinson's disease. Mov Disord. 2018 Apr;33(4):568-574. doi: 10.1002/mds.27275. Epub 2018 Jan 30. No abstract available.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
February 9, 2016
Primary Completion (Actual)
September 22, 2020
Study Completion (Actual)
September 22, 2020
Study Registration Dates
First Submitted
January 7, 2016
First Submitted That Met QC Criteria
January 11, 2016
First Posted (Estimate)
January 14, 2016
Study Record Updates
Last Update Posted (Actual)
November 7, 2022
Last Update Submitted That Met QC Criteria
November 4, 2022
Last Verified
March 1, 2021
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Parkinsonian Disorders
- Basal Ganglia Diseases
- Movement Disorders
- Synucleinopathies
- Neurodegenerative Diseases
- Parkinson Disease
- Molecular Mechanisms of Pharmacological Action
- Chelating Agents
- Sequestering Agents
- Iron Chelating Agents
- Deferiprone
Other Study ID Numbers
- 2015_22
- 2015-003679-31 (EudraCT Number)
- Grant agreement No 633190 (Other Grant/Funding Number: European Union's Horizon 2020)
- HP751 (Other Identifier: CTFG VHP)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Undecided
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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