Neurodegenerative DiseasePhase 2NCT00907283
Ferrochelating Treatment in Patients Affected by Neurodegeneration With Brain Iron Accumulation (NBIA)
A Phase 2 study testing Deferiprone in people with Neurodegenerative Disease and Iron Overload, run by Ente Ospedaliero Ospedali Galliera at 3 sites in Italy.
Trial summary
This trial is a multicenter, unblinded, single-arm pilot study, lasting one year (plus one year extension Amendment n.3 25 August 2009, plus two years follow-up Amendment n.7) , to evaluate the efficacy and safety of the chelator therapy with deferiprone on cerebral iron accumulations. Read more about this study
- Who is it for?
- Ages 1 year to 80 years
- Conditions the study is for
- Neurodegenerative Disease, Iron Overload
- What is being tested?
- Deferiprone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 3 sitesItaly
- Study dates
- Nov 2008to Dec 2024
- Phase
- Phase 2
- 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 1 year to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients over > 1 years of age who have neurological symptoms that can be correlated with cerebral-level iron overload as documented with MRI.This inclusion criteria has been amended by Amendment 6, 24 march 2011)
- Patients who have given informed consent.
Who cannot join
- Inability to be subjected to MRI exam.
- Renal insufficiency (creatinine > 1.5 mg/dl).
- Neoplasias.
- Patients with average levels of ALT > 300 and patients with variations of ALT or AST of 300% during the year prior to enrolling. (At least 4 measurements in 12 months).
- Systemic cardiovascular, renal, hepatic etc., diseases that could counter-indicate the therapeutic options specified.
- Known hypersensitivity to deferiprone.
- Patient judged potentially unreliable and/or uncooperative with regard to study procedures.
- Pregnancy and breastfeeding.
Trial locations and contacts
3 sites in 1 country.
Italy3 sites
Neurological Pathology Department, Brotzu Hospital
Cagliari, 09134
Centre of Microcitemia and Congenital Anemias, Galliera Hospital
Genoa, 16128
Clinic of Neurology, University of Genoa
Genoa, 16132
About this study
Official title: Ferrochelating Treatment in Patients Affected by "Neurodegeneration With Brain Iron Accumulation" (NBIA)
This trial is a multicenter, unblinded, single-arm pilot study, lasting one year (plus one year extension Amendment n.3 25 August 2009, plus two years follow-up Amendment n.7) , to evaluate the efficacy and safety of the chelator therapy with deferiprone on cerebral iron accumulations. The drug will be administered in the dosage of 15 mg/kg twice daily. The safety and tolerability of the drug will be evaluated by measuring hemochrome every seven days with leukocyte formula count.
At 3, 6 and 12 months from the start of treatment, a neurological evaluation will be performed using several specific evaluation scales (International Cooperative Ataxia Rating Scale (ICARS); Unified Parkinson's Disease Rating Scale (UPDRS); Burke-Fahn-Marsden (BFM)).
Every 6 months of treatment, a brain magnetic resonance image (MRI) aimed at measuring iron overload quantitatively, if possible.
Read the detailed description
The time interval between Study Start Date and Study First Received was related to bureaucratic problems.
The treatment of systemic iron overload has in recent years improved notably since new drugs and new therapeutic combinations have become available for use. Conversely, therapies for the removal of regional iron overloads on the cerebral level have not been described in the literature.
As it is known, the symptoms resulting from a cerebral iron overload are strongly disabling, reducing the patient's autonomy. Considering that valid therapeutic alternatives of proven preventive and/or curative efficacy in these neurodegenerative diseases do not exist today, the use of lipophilic iron chelators must be considered as a possible therapeutic strategy worthy of deeper study.
Deferiprone is an oral active iron chelator, the use of which is authorized for the treatment of iron overload in patients affected by thalassemia major in conditions of "chelation not suitable for Desferal." In recent years, deferiprone has been applied extensively, demonstrating a good efficacy and tolerability profile.
Unlike deferoxamine, a hydrophilic drug, deferiprone presents chemical-physical characteristics (low molecular weight, favourable octanol:water partition coefficient, neutral charge) that guarantee drug good permeability of mitochondrial walls and the blood-brain barrier.
In a recent study deferiprone (commercial name Ferriprox) was used in 13 patients with Friedreich's ataxia (FA), also treated with idebenone (an experimental drug with an anti-oxidant action), compared with 9 patients affected by FA but treated only with Idebenone. The 9 patients who completed the 6 months of treatment with deferiprone were evaluated from a clinical point of view using the ICARS Scale (International Cooperative Ataxia Rating Score) before the start and after 1 and 6 months of therapy. They also performed a cerebral Magnetic Resonance Imaging before and after 1, 2, 4 and 6 months of treatment. The results were promising. In fact, after 6 months of therapy, a reduction in iron accumulation in specific cerebral areas involved in the pathogenesis of neurodegenerative disease was demonstrated. The patients also presented a significant clinical improvement confirmed by the ICARS score.
Therefore the use of deferiprone, despite the possible side effects (such as gastrointestinal disturbances, a temporary increase in transaminases, and especially agranulocytosis found in about 1% of patients treated with deferiprone), currently represents the only possibility for removing and/or preventing the accumulation of iron in the central nervous system, curing and/or avoiding the most severe and debilitating consequences of a disease for which another therapy does not exist.
The Centers that specialize in the treatment of iron accumulation have acquired significant experience in the use of new oral iron chelators over the last 10 years, which permits deferiprone to be used carefully and safely in the three cases at hand. We therefore propose the use of this drug for treating patients who show neurological symptoms that can be correlated with a cerebral iron overload shown through MRI and who have not benefited from other therapies.
- Conditions
- Neurodegenerative Disease, Iron Overload
- Being tested
- Deferiprone
- Keywords
- NBIA, Iron overload AND brain, Iron chelation AND neurodegeneration, Brain iron Overload, Neurodegeneration, Brain iron Accumulation
- Medical subject headings
- Neurodegenerative Diseases, Iron Overload, Nerve Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DeferiproneDrug
Also called EU/1/99/108/002 Ferriprox 100 mg/ml Oral solution, EU/1/99/108/003 Ferriprox 100 mg/ml Oral solution
15 mg/Kg/twice for 1 year
| Study group | Role | What they receive |
|---|---|---|
| deferiprone | Experimental | 15 mg/Kg/twice for 1 year Receives: Drug: Deferiprone |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the efficacy and safety of the chelator therapy with deferiprone on cerebral iron accumulations.
Safety:CBC including ANC will be monitored weekly.If the liver enzymes are greater than 2.5 fold the upper limit of normal, the drug will be withheld and the assessment repeated in 1 week. If the laboratory values continue to be over 2.5 times the upper limit of normal or if the neutrophil counts decrease to less than 1.5 x 109/L (1500 cells/µl) the Patient will be withdrawn from the study. Neutropenia/Agranulocytosis is confirmed as an Absolute Neutrophil Count being less than 1.5 x 109/L (1500 cells/µl) if counts on two consecutive days are both less than 1.5 x 109 (1500 cells/µl).
Measured: 6 months + 6 months (plus one year extension)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2009 (estimated)
- Study startNov 2008
- Primary completionDec 2024 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Neurodegenerative DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ente Ospedaliero Ospedali Galliera
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Gian Luca Forni, Ente Ospedaliero Ospedali Galliera
- Investigators
- Gian Luca Forni, MD, Principal investigator, E.O. Ospedali Galliera. Centro della Microcitemia e delle Anemie Congenite -Ematology - Genoa Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00907283
- Sponsor's protocol ID
- Deferiprone08
- Other IDs
- EUDRACT NUMBER 2008-005206-39
- Status last verified
- Feb 2023
- First submitted
- 21 May 2009
- Last updated
- 9 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
Publications
Forni GL, Balocco M, Cremonesi L, Abbruzzese G, Parodi RC, Marchese R. Regression of symptoms after selective iron chelation therapy in a case of neurodegeneration with brain iron accumulation. Mov Disord. 2008 Apr 30;23(6):904-7. doi: 10.1002/mds.22002.
PubMed 18383118Abbruzzese G, Cossu G, Balocco M, Marchese R, Murgia D, Melis M, Galanello R, Barella S, Matta G, Ruffinengo U, Bonuccelli U, Forni GL. A pilot trial of deferiprone for neurodegeneration with brain iron accumulation. Haematologica. 2011 Nov;96(11):1708-11. doi: 10.3324/haematol.2011.043018. Epub 2011 Jul 26.
PubMed 21791473
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ferrochelating Treatment in Patients Affected by "Neurodegeneration With Brain Iron Accumulation" (NBIA)
- ClinicalTrials.gov ID
- NCT00907283
- Acronym / sponsor ID
- Deferiprone08
- Conditions
- Neurodegenerative Disease, Iron Overload
- Keywords
- NBIA, Iron overload AND brain, Iron chelation AND neurodegeneration, Brain iron Overload, Neurodegeneration, Brain iron Accumulation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Ente Ospedaliero Ospedali GallieraUniversity, hospital or other
- Study start
- Nov 2008
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 22 May 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial is a multicenter, unblinded, single-arm pilot study, lasting one year (plus one year extension Amendment n.3 25 August 2009, plus two years follow-up Amendment n.7) , to evaluate the efficacy and safety of the chelator therapy with deferiprone on cerebral iron accumulations. The drug will be administered in the dosage of 15 mg/kg twice daily. The safety and tolerability of the drug will be evaluated by measuring hemochrome every seven days with leukocyte formula count.
At 3, 6 and 12 months from the start of treatment, a neurological evaluation will be performed using several specific evaluation scales (International Cooperative Ataxia Rating Scale (ICARS); Unified Parkinson's Disease Rating Scale (UPDRS); Burke-Fahn-Marsden (BFM)).
Every 6 months of treatment, a brain magnetic resonance image (MRI) aimed at measuring iron overload quantitatively, if possible.
Detailed description
The time interval between Study Start Date and Study First Received was related to bureaucratic problems.
The treatment of systemic iron overload has in recent years improved notably since new drugs and new therapeutic combinations have become available for use. Conversely, therapies for the removal of regional iron overloads on the cerebral level have not been described in the literature.
As it is known, the symptoms resulting from a cerebral iron overload are strongly disabling, reducing the patient's autonomy. Considering that valid therapeutic alternatives of proven preventive and/or curative efficacy in these neurodegenerative diseases do not exist today, the use of lipophilic iron chelators must be considered as a possible therapeutic strategy worthy of deeper study.
Deferiprone is an oral active iron chelator, the use of which is authorized for the treatment of iron overload in patients affected by thalassemia major in conditions of "chelation not suitable for Desferal." In recent years, deferiprone has been applied extensively, demonstrating a good efficacy and tolerability profile.
Unlike deferoxamine, a hydrophilic drug, deferiprone presents chemical-physical characteristics (low molecular weight, favourable octanol:water partition coefficient, neutral charge) that guarantee drug good permeability of mitochondrial walls and the blood-brain barrier.
In a recent study deferiprone (commercial name Ferriprox) was used in 13 patients with Friedreich's ataxia (FA), also treated with idebenone (an experimental drug with an anti-oxidant action), compared with 9 patients affected by FA but treated only with Idebenone. The 9 patients who completed the 6 months of treatment with deferiprone were evaluated from a clinical point of view using the ICARS Scale (International Cooperative Ataxia Rating Score) before the start and after 1 and 6 months of therapy. They also performed a cerebral Magnetic Resonance Imaging before and after 1, 2, 4 and 6 months of treatment. The results were promising. In fact, after 6 months of therapy, a reduction in iron accumulation in specific cerebral areas involved in the pathogenesis of neurodegenerative disease was demonstrated. The patients also presented a significant clinical improvement confirmed by the ICARS score.
Therefore the use of deferiprone, despite the possible side effects (such as gastrointestinal disturbances, a temporary increase in transaminases, and especially agranulocytosis found in about 1% of patients treated with deferiprone), currently represents the only possibility for removing and/or preventing the accumulation of iron in the central nervous system, curing and/or avoiding the most severe and debilitating consequences of a disease for which another therapy does not exist.
The Centers that specialize in the treatment of iron accumulation have acquired significant experience in the use of new oral iron chelators over the last 10 years, which permits deferiprone to be used carefully and safely in the three cases at hand. We therefore propose the use of this drug for treating patients who show neurological symptoms that can be correlated with a cerebral iron overload shown through MRI and who have not benefited from other therapies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| deferiprone | Experimental | Drug: Deferiprone15 mg/Kg/twice for 1 year |
Who may qualify
- Ages
- 1 year to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Patients over > 1 years of age who have neurological symptoms that can be correlated with cerebral-level iron overload as documented with MRI.This inclusion criteria has been amended by Amendment 6, 24 march 2011)
- Patients who have given informed consent.
Key exclusion criteria (8 listed)
- Inability to be subjected to MRI exam.
- Renal insufficiency (creatinine > 1.5 mg/dl).
- Neoplasias.
- Patients with average levels of ALT > 300 and patients with variations of ALT or AST of 300% during the year prior to enrolling. (At least 4 measurements in 12 months).
- Systemic cardiovascular, renal, hepatic etc., diseases that could counter-indicate the therapeutic options specified.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DeferiproneAlso: EU/1/99/108/002 Ferriprox 100 mg/ml Oral solution, EU/1/99/108/003 Ferriprox 100 mg/ml Oral solution15 mg/Kg/twice for 1 year | Drug | deferiprone |
Primary outcome
To evaluate the efficacy and safety of the chelator therapy with deferiprone on cerebral iron accumulations.
Time frame: 6 months + 6 months (plus one year extension)
Safety:CBC including ANC will be monitored weekly.If the liver enzymes are greater than 2.5 fold the upper limit of normal, the drug will be withheld and the assessment repeated in 1 week. If the laboratory values continue to be over 2.5 times the upper limit of normal or if the neutrophil counts decrease to less than 1.5 x 109/L (1500 cells/µl) the Patient will be withdrawn from the study. Neutropenia/Agranulocytosis is confirmed as an Absolute Neutrophil Count being less than 1.5 x 109/L (1500 cells/µl) if counts on two consecutive days are both less than 1.5 x 109 (1500 cells/µl).
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2023.
- Background: PubMed 18383118Forni GL, Balocco M, Cremonesi L, Abbruzzese G, Parodi RC, Marchese R. Regression of symptoms after selective iron chelation therapy in a case of neurodegeneration with brain iron accumulation. Mov Disord. 2008 Apr 30;23(6):904-7. doi: 10.1002/mds.22002.
- Results publication: PubMed 21791473Abbruzzese G, Cossu G, Balocco M, Marchese R, Murgia D, Melis M, Galanello R, Barella S, Matta G, Ruffinengo U, Bonuccelli U, Forni GL. A pilot trial of deferiprone for neurodegeneration with brain iron accumulation. Haematologica. 2011 Nov;96(11):1708-11. doi: 10.3324/haematol.2011.043018. Epub 2011 Jul 26.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gian Luca Forni, MD principal investigator
E.O. Ospedali Galliera. Centro della Microcitemia e delle Anemie Congenite -Ematology - Genoa Italy
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Deferiprone in people with Neurodegenerative Disease and Iron Overload, run by Ente Ospedaliero Ospedali Galliera at 3 sites in Italy.
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 2 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 9 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Italy. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
To evaluate the efficacy and safety of the chelator therapy with deferiprone on cerebral iron accumulations. (time frame: 6 months + 6 months (plus one year extension)). 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 NCT00907283, 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 9 Feb 2023.