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Trial record 52 of 68 for:    Recruiting, Active, not recruiting Studies | Parkinson Disease | France

Conservative Iron Chelation as a Disease-modifying Strategy in Parkinson's Disease (FAIRPARKII)

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ClinicalTrials.gov Identifier: NCT02655315
Recruitment Status : Recruiting
First Posted : January 14, 2016
Last Update Posted : November 9, 2017
Sponsor:
Collaborators:
European Commission
ApoPharma
Information provided by (Responsible Party):
University Hospital, Lille

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Parkinson Disease Drug: Deferiprone Drug: Placebo Phase 2

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  (Clinical Trial)
Estimated Enrollment : 338 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Conservative Iron Chelation as a Disease-modifying Strategy in Parkinson's Disease. European Multicentre, Parallel-group, Placebo-controlled, Randomized Clinical Trial of Deferiprone"
Study Start Date : February 2016
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Deferiprone

Arm Intervention/treatment
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.
Drug: Deferiprone
15 mg / kg twice daily morning and evening (30mg / kg per day).The treatment lasts nine months.
Other Name: active drug

Placebo Comparator: PLACEBO
Half of participants will receive the placebo twice daily morning and evening. The treatment lasts nine months.
Drug: Placebo
the placebo twice daily morning and evening. The treatment lasts nine months
Other Names:
  • harmless pill
  • inactive drug




Primary Outcome Measures :
  1. Global effect (symptomatic and disease modifying effects) on motor and non motor handicap [ Time Frame: at 36 weeks ]
    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)


Secondary Outcome Measures :
  1. Disease-modifying effect on motor and non motor handicap [ Time Frame: baseline, at 40 weeks ]
    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

  2. Effect of the motor symptoms [ Time Frame: baseline, at 12, 36 and 40 weeks ]
    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

  3. Quality of life and autonomy by PDQ-39 score [ Time Frame: baseline, at 36 and 40 weeks ]
    It will be analyzed as the change in the Parkinson's Disease Quality of Life (PDQ-39, via a 39-item self-questionnaire)

  4. Quality of life and autonomy by Clinical Global Impression score [ Time Frame: baseline, at 36 and 40 weeks ]
    the Clinical Global Impression scored by the examiner and the patient

  5. Health economics assessment [ Time Frame: baseline, at 36 and 40 weeks ]
    will be performed via a specific questionnaire provides a simple descriptive profile and a single index value for health status

  6. EQ-5D questionnaire [ Time Frame: baseline, at 36 and 40 weeks ]
    the questionnaire provides a simple descriptive profile and a single index value for health status.

  7. Safety criteria [ Time Frame: 40 weeks ]

    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

    • adverse events
    • neutropenia (weekly complete blood count)
    • agranulocytosis (weekly complete blood count)
    • anemia (weekly complete blood count)
    • iron metabolism abnormalities (haemoglobin, serum iron, ferritinemia, transferrin, total binding capacity, transferrin saturation coefficient, 24-hour urine iron).
    • Standard biological abnormalities (fasting glucose, urea, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and (for all sexually active, fertile females) urine pregnancy tests.
    • Abnormal physical examination (including vital signs, bodyweight, electrocardiogram and blood pressure)

  8. Effect on overall cognitive status [ Time Frame: baseline, at 12, 36 and 40 weeks ]
    Measured by the score in the Montreal Cognitive Assessment

  9. Effect on gait disorders [ Time Frame: baseline, at 12, 36 and 40 weeks ]
    Measured by the Stand Walk Sit test

  10. Effect on daily living [ Time Frame: baseline, at 12, 36 and 40 weeks ]
    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

  11. Effect on non-motor symptoms [ Time Frame: baseline, at 12, 36 and 40 weeks ]
    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

  12. Lack of occurrence of motor fluctuations [ Time Frame: baseline, at 12, 36 and 40 weeks ]
    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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Ages Eligible for Study:   up to 80 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adult patients
  2. 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.
  3. 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).
  4. Patients covered by a Health Insurance System in countries where required by law
  5. Written informed consent dated and signed prior to the beginning of any procedures related to the clinical trial

Exclusion Criteria:

  1. Disease duration greater than 18 months.
  2. Patients with high frequency of comorbidity or vital risks that may reasonably impair life expectancy
  3. Subject with handicap required dopaminergic treatment at the inclusion and therefore likely not to bear 9 months without symptomatic treatment
  4. Hoehn and Yahr stage 3 or more.
  5. 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).
  6. 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).
  7. 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.
  8. Subjects undergoing brain stimulation.
  9. Positive Human Immunodepression Virus serology.
  10. Hypersensitivity to deferiprone.
  11. Patients with agranulocytosis or with a history of agranulocytosis.
  12. Patients taking a treatment at risk of agranulocytosis (clozapine, Closaril®/Leponex®).
  13. Patients with anaemia (regardless of the latter's aetiology) or a history of another haematological disease. Haemochromatosis is not an exclusion criterion.
  14. Pregnant or breastfeeding women or women of childbearing potential not taking highly effective contraception.
  15. Kidney or liver failure.
  16. Other serious diseases.
  17. Inability to provide informed consent.
  18. Participation in another clinical trial with investigational medicinal product within 3 months prior to inclusion in the study
  19. Patient who has suffered mild or moderate depressive episode and isn't in remission and on a stable medication for at least 8 weeks
  20. 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)

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): NCT02655315


Contacts
Contact: David Devos, MD,PhD david.devos@chru-lille.fr
Contact: Pauline Guyon, Project Manager pauline.guyon@chru-lille.fr

Locations
Austria
Medizinische Universitat Innsbruck Recruiting
Innsbruck, Austria
Principal Investigator: Werner Poewe, MD, PhD         
Czechia
Univerzita Karlova V Praze Recruiting
Prague, Czechia
Principal Investigator: Evzen Ruzicka, MD,PhD         
Charles University Recruiting
Praha, Czechia
Principal Investigator: Evzen Ruzicka, MD         
France
CHU Pellegrin Recruiting
Bordeaux, France
Principal Investigator: Wassilios Meissner, MD,PhD         
Hôpital Wertheimer Recruiting
Bron, France
Principal Investigator: Stéphane Thobois, MD,PhD         
Hôpital Montpied Recruiting
Clermont-Ferrand, France
Principal Investigator: Frank Durif, MD,PhD         
Hôpital Salengro, CHRU Recruiting
Lille, France
CHU la TIMONE Recruiting
Marseille, France
Principal Investigator: Alexandre Eusebio, MD, PhD         
AP-HP, Hôpital Pitié-Salpêtrière Recruiting
Paris, France
Principal Investigator: Jean-Christophe Corvol, MD, PhD         
CHU de Strasbourg, Hôpital de Hautepierre Recruiting
Strasbourg, France
Principal Investigator: Christine Tranchant, MD,PhD         
Chu Purpan Recruiting
Toulouse, France
Principal Investigator: Olivier Rascol, MD,PhD         
Germany
University Hospital, Saarland University Not yet recruiting
Homburg, Germany
Principal Investigator: Stefanie Behnke, MD         
Christian-albrechts universität zu kiel Recruiting
Kiel, Germany
Principal Investigator: Daniela Berg, MD,PhD         
Klinik und Poliklinik für Neurologie der Universitätsmedizin Rostock Recruiting
Rostock, Germany
Principal Investigator: Uwe Walter, MD,PhD         
Netherlands
Acadamic central center, Amsterdam Recruiting
Amsterdam, Netherlands
Principal Investigator: Rob De Bie, MD         
Radboud university medical center Recruiting
Nijmegen, Netherlands
Principal Investigator: Bart Post, MD         
Portugal
Centro Hospitalar e universitario de Coimbra Not yet recruiting
Coimbra, Portugal
Principal Investigator: Cristina Januario, MD         
Centro Hospitalar do Alto Ave Recruiting
Guimarães, Portugal
Principal Investigator: Miguel Gago, MD         
Centro Hospitalar Lisboa Norte Not yet recruiting
Lisbon, Portugal
Principal Investigator: Joaquim Ferreira, MD         
Spain
Hospital Clinic Universitari de Barcelona Recruiting
Barcelona, Spain
Principal Investigator: Eduard Tolosa, MD,PhD         
Hospital de Bellvitge Not yet recruiting
Barcelona, Spain
Principal Investigator: Matilde Calopa, MD,Phd         
Hospital de la Santa Creu i Sant Pau Recruiting
Barcelona, Spain
Principal Investigator: Jaime Kulisevsky, MD,PhD         
United Kingdom
Cambridge University Hospital Not yet recruiting
Cambridge, United Kingdom
Principal Investigator: Paul Worth, MD         
University of Glasgow Terminated
Glasgow, United Kingdom
Newcastle University Not yet recruiting
Newcastle, United Kingdom
Principal Investigator: David Burn, MD,PhD         
Sponsors and Collaborators
University Hospital, Lille
European Commission
ApoPharma
Investigators
Study Chair: David Devos, MD, PhD University Hospital, Lille

Additional Information:
Responsible Party: University Hospital, Lille
ClinicalTrials.gov Identifier: NCT02655315     History of Changes
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 )
First Posted: January 14, 2016    Key Record Dates
Last Update Posted: November 9, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by University Hospital, Lille:
Parkinson
Deferiprone
Chelation

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Deferiprone
Iron Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action