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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02655315
Recruitment Status : Active, not recruiting
First Posted : January 14, 2016
Last Update Posted : March 10, 2021
Sponsor:
Collaborators:
European Commission
ApoPharma
Information provided by (Responsible Party):
University Hospital, Lille

Tracking Information
First Submitted Date  ICMJE January 7, 2016
First Posted Date  ICMJE January 14, 2016
Last Update Posted Date March 10, 2021
Actual Study Start Date  ICMJE February 9, 2016
Estimated Primary Completion Date February 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 11, 2016)
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)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 11, 2016)
  • 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
  • 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
  • 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)
  • 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
  • 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
  • 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.
  • 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)
  • Effect on overall cognitive status [ Time Frame: baseline, at 12, 36 and 40 weeks ]
    Measured by the score in the Montreal Cognitive Assessment
  • Effect on gait disorders [ Time Frame: baseline, at 12, 36 and 40 weeks ]
    Measured by the Stand Walk Sit test
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Conservative Iron Chelation as a Disease-modifying Strategy in Parkinson's Disease
Official Title  ICMJE Conservative Iron Chelation as a Disease-modifying Strategy in Parkinson's Disease. European Multicentre, Parallel-group, Placebo-controlled, Randomized Clinical Trial of Deferiprone"
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Parkinson Disease
Intervention  ICMJE
  • Drug: Deferiprone
    15 mg / kg twice daily morning and evening (30mg / kg per day).The treatment lasts nine months.
    Other Name: active drug
  • Drug: Placebo
    the placebo twice daily morning and evening. The treatment lasts nine months
    Other Names:
    • harmless pill
    • inactive drug
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Deferiprone
  • Placebo Comparator: PLACEBO
    Half of participants will receive the placebo twice daily morning and evening. The treatment lasts nine months.
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 25, 2020)
372
Original Estimated Enrollment  ICMJE
 (submitted: January 11, 2016)
338
Estimated Study Completion Date  ICMJE February 2022
Estimated Primary Completion Date February 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 80 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Czechia,   France,   Germany,   Netherlands,   Portugal,   Spain,   United Kingdom
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT02655315
Other Study ID Numbers  ICMJE 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 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party University Hospital, Lille
Study Sponsor  ICMJE University Hospital, Lille
Collaborators  ICMJE
  • European Commission
  • ApoPharma
Investigators  ICMJE
Study Chair: David Devos, MD, PhD University Hospital, Lille
PRS Account University Hospital, Lille
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP