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Parkinson's DiseasePhase 2/3FAIR-PARK-INCT00943748

Efficacy and Safety of the Iron Chelator Deferiprone in Parkinson's Disease

A Phase 2/3 study testing deferiprone in people with Parkinson's Disease, run by University Hospital, Lille at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Few available drugs can slow the progression of neurodegenerative pathologies such as Parkinson's disease (PD). One of the recent hypotheses concerning the reduction of oxidative stress and neuron death features a harmful effect of iron, which may reach abnormally high levels in the substantia nigra (SN) pars compacta… Read more about this study

Who is it for?
Ages 30 to 80 years
Conditions the study is for
Parkinson's Disease
What is being tested?
deferiprone
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
40 participants
Where
1 siteFrance
Study dates
Oct 2009to Oct 2011
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 30 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with typical Parkinson's disease according to the Gibb criteria and the Parkinson's Disease Society criteria (Daniel and Lees, 1993).
  • Ideally less than 2 to 3 years since disease onset and never more than 4 years.
  • Patients on dopaminergic drugs and/or L-Dopa.
  • Non-fluctuating disease because otherwise the degenerative process would be well advanced, the clinical score would vary from one day to another and the imaging evaluation would be complicated by dyskinesia.

Who cannot join

  • Subjects over the age of 80
  • Demented subjects: MMSE score ≤ 24, Mattis score of < 130 and DSM IV criteria
  • Subjects with radiological anomalies on MRI, whether incidental or suggestive of vascular involvement or significant cortical or subcortical atrophy
  • Subjects for whom MRI is contra-indicated (metal objects in the body, severe claustrophobia, pacemaker, etc.)
  • Subjects undergoing brain stimulation
  • Very severe rest tremor, which could induce MRI artifacts
Show all 21Show fewer
  • Subjects that have not stabilized in terms of the therapeutic regimen and who are likely to require changes in their dopamine therapy in the coming 6 months
  • Hoehn and Yahr stage ≥ 3 in the "Off" state, indicating the need for walking assistance in the absence of treatment.
  • Hypersensitivity to iron chelator drugs
  • Patients at risk of or having experienced agranulocytosis
  • Patients on a drug that can potentially induce agranulocytosis (clozapine, Closaril®/Leponex®)
  • Patients with anemia (regardless of the latter's etiology) or a history of other hematological diseases - even an iron deficiency
  • Ferritin blood level < 100 ng/ml (100 µg/l)
  • A history of hemochromatosis or known iron metabolism disorders.
  • Pregnant or breastfeeding women or women not taking effective contraception
  • Kidney or liver failure
  • Blood coagulation disorders, antiplatelet drugs or anticoagulants
  • Concomitant treatment with aluminum-based antacids (interaction)
  • Concomitant treatment with vitamin C (interaction)
  • Presence of other serious diseases
  • Inability to provide informed consent

Trial locations and contacts

1 site in 1 country.

France1 site
  • Service de Neurologie, Clinique Neurologique, EA 2683, IFR 114

    Lille, 59037

Other trials in France

About this study

Official title: Efficacy and Safety of the Iron Chelator Deferiprone on Iron Overload in the Brain in Parkinson's Disease

Few available drugs can slow the progression of neurodegenerative pathologies such as Parkinson's disease (PD). One of the recent hypotheses concerning the reduction of oxidative stress and neuron death features a harmful effect of iron, which may reach abnormally high levels in the substantia nigra (SN) pars compacta (iron overload has been seen in the substantia nigra in parkinsonian patients and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD). Iron overload is harmful because it reacts with hydrogen peroxide (H2O2) produced during the oxidative deamination of dopamine, generating hydroxyl radicals which then damage proteins, DNA and phospholipid membranes and may be responsible for neuron death. The use of an iron chelator (clioquinol) produces a reduction in neuron death in the MPTP mouse model. In humans, a special, partially refocused interleaved multiple echo (PRIME) MR sequence has been used to study the relaxation time (T2*) and quantify iron overload in the SN of PD patients and the nucleus dentatus of patients with Friedreich's ataxia. T2* sequences have revealed a decrease in iron overload following treatment with the chelator deferiprone, in parallel with a clinical improvement in these patients. Furthermore, the very recent open label use of deferiprone in rare serious, systemic, neurological iron overload diseases (Neurodegeneration with Brain Iron Accumulation (NBIA)) has revealed a clinical improvement after 6 months, with 2 case reports from our group and another from an Italian group (Forni et al., 2008). The safety of the low dosages of deferiprone (20 to 30 mg/kg/day) used in neurology appears to be much greater than for the high dosages (75 to 100 mg/kg/day in 3 doses) used in hematology to decrease post-transfusion iron overloads in thalassemia major.

Hence, the investigators wish to evaluate the effect of treatment with an oral iron chelator which is capable of crossing the blood-brain barrier (deferiprone) on iron overload in the SN(as assessed by the T2* sequence) with respect to the progression of clinical sign in PD. It is expected a 6-month course of deferiprone able to produce a moderate reduction in iron overload of the SN, associated with a drop in the motor handicap score. Depending on the risk/benefit balance determined in this initial pilot study, a larger, multicenter neuroprotection study could be envisaged.

Read the detailed description

Primary objective: decrease the iron overload (as measured by the T2* MRI sequence) in the substantia nigra in patients with Parkinson's disease (PD) after 6 months of deferiprone treatment, relative to the placebo group.

Secondary objectives:

  1. Other radiological criteria: Modification of T2* in MRI of the caudal nucleus head, putamen and pallidum.
  2. Evaluate the "disease modifier" effect on the clinical symptoms:
  • Parkinsonian syndrome: UPDRS III
  • the Clinical Global Impression scored by the examiner and the patient.
  1. Evaluate the safety on cognitive and behavioral functions
  • MDS-UPDRS I
  • overall cognitive function (Mattis, MMSE), memory, executive function, attention (simple and choice reaction times)
  • drowsiness and sleep (Epworth scale, Parkinson Disease Sleep Scale), depression (MADRS).
  1. Safety: complete blood count (CBC) with weekly leukocyte counts, standard blood biochemistry profile, blood iron profile, ECG, blood pressure, bodyweight, adverse event reporting.
  2. Specific biochemistry screen: heavy metal profile, oxidative stress and dopamine metabolism.

Study center: Service de Neurologie et Pathologie du Mouvement (Head: Prof. Destée, Clinique Neurologique and Service de Neuroradiologie (Head: Prof. Pruvo), Salengro Hospital, Lille University Medical Center, Lille, France.

Study characteristics: a randomized, double-blind, placebo-controlled, parallel-group, single-center trial with a delayed onset paradigm (Early-start group with 12 months of deferiprone versus delayed -start group with 6 months of placebo then 6 months of deferiprone) to study the effect of deferiprone on the relaxation time of the substantia nigra during a T2* MRI sequence (R2*=1/T2* reflecting iron overload) with respect to motor disorders in Parkinson's disease.

Active compound: the iron chelator 1,2-dimethyl-3-hydroxy-4-pyridinone (deferiprone, FERRIPROX®), which decreases abnormally high iron and ferritin levels. Its low molecular weight and liposolubility enable it to cross the blood-brain barrier.

Posology: the recommended dosage in neurology is a total of 30 mg/kg/day, in 2 doses.

Study population: 40 adult parkinsonian volunteers, with early-stage PD under their first optimised dopaminergic therapeutic strategy (i.e. either dopamine agonist and/or slight dose of L-dopa) and free of motor fluctuations or dementia.

Planned inclusion period: 12 months. Study duration for individual patients: 13 months (2 weeks between screening and randomization, 6 months of double-blind treatment, then 6 months of open label treatment and then a 2-week wash-out period).

Study procedures and timeline:

  • A screening visit (Sc).
  • Two comprehensive examinations (a neurological and neuropsychological check-up) at the randomization visit (V0, at D7-15 ± 1 week after Sc), visit after 6 months (V6, at least 6 months after V0), visit after 12 months (V12, at least 12 months after V0)
  • Weekly monitoring of the CBC with the leukocyte count, results faxed by the patient's local clinical lab or Lille University Medical Center's central lab.
  • Monitoring of blood iron and zinc status and overall tolerance during a brief consultation: V1, V3, V5, V7, V9, V11
  • MRI in an external facility at V0, V6, V12.
  • Telephone follow-up: V2, V4, V8, V10
  • Patients will be invited to participate in an ancillary study involving analysis of the cerebrospinal fluid (CSF) at the randomization visit and the V6, in order to perform a full set of CSF biochemistry assays and with a view to determining biological benefits at the central nervous system level and identifying biological markers.
Being tested
deferiprone, placebo
Medical subject headings
Parkinson Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • deferiproneDrug

    Also called FERRIPROX

    A standard dose-escalation phase will be initiated, with a 3 ml of the deferiprone oral solution twice a day (breakfast and dinner) increase every 3 days up to a total of a fixed dose of 9 ml of deferiprone oral solution twice a day corresponding to 30 mg/kg/day in 2 doses

  • placeboDrug

    A standard dose-escalation phase will first be initiated, with a 3 ml of the placebo oral solution twice a day (breakfast and dinner) increase every 3 days up to a total of a fixed dose of 9 ml of placebo oral solution twice a day corresponding to 30 mg/kg/day in 2 doses

Study groups in NCT00943748
Study groupRoleWhat they receive
deferiproneActive comparatordeferiprone 30 mg/kg/day
Receives: Drug: deferiprone
placeboPlacebo comparatorplacebo : 30 mg/kg/day, in 2 liquid doses
Receives: Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Decrease the iron overload (as measured by the T2* MRI sequence) in the substantia nigra in patients with Parkinson's disease (PD) after 6 months of deferiprone treatment, relative to the placebo group.

    Measured: 6 months and 12 months

Secondary outcomes (7)
  1. Other radiological criteria: Modification of T2* in MRI of the caudal nucleus head, putamen and pallidum

    Measured: 6 and 12 months

  2. Parkinsonian syndrome: UPDRS III

    Measured: 6 and 12 months

  3. Cognitive and behavioral functions: function, attention (simple and choice reaction times), drowsiness and sleep (Epworth scale, Parkinson Disease Sleep Scale), depression (MADRS).

    MDS-UPDRS I, overall cognitive function (Mattis, MMSE), memory, executive

    Measured: 6 months and 12 months

  4. The Clinical Global Impression scored by the examiner and the patient

    Measured: 6 months and 12 months

  5. Specific biochemistry screen: heavy metal profile, oxidative stress and dopamine metabolism

    Measured: 6 and 12 months

  6. Complete blood count (CBC) with weekly leukocyte counts, standard blood biochemistry profile, blood iron profile, ECG, blood pressure, bodyweight, adverse event reporting.

    Measured: 6 and 12 months

  7. Ancillary study involving analysis of the cerebrospinal fluid (CSF).

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jul 2009 (estimated)
  2. Study startOct 2009
  3. Primary completionAug 2011
  4. Study completionOct 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00943748
Sponsor's protocol ID
2008-006842-25
Other IDs
2008_19/0838, A90113-62, 2008
Acronym
FAIR-PARK-I
Status last verified
Jul 2009
First submitted
20 Jul 2009
Last updated
14 May 2026
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 24251381
  • Grolez G, Moreau C, Sablonniere B, Garcon G, Devedjian JC, Meguig S, Gele P, Delmaire C, Bordet R, Defebvre L, Cabantchik IZ, Devos D. Ceruloplasmin activity and iron chelation treatment of patients with Parkinson's disease. BMC Neurol. 2015 May 6;15:74. doi: 10.1186/s12883-015-0331-3.

    PubMed 25943368

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing deferiprone in people with Parkinson's Disease, run by University Hospital, Lille at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Decrease the iron overload (as measured by the T2* MRI sequence) in the substantia nigra in patients with Parkinson's disease (PD) after 6 months of deferiprone treatment, relative to the placebo group. (time frame: 6 months and 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00943748, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2026.

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