Try the modernized beta website. Learn more about the modernization effort.
Working… Menu

Ferrochelating Treatment in Patients Affected by Neurodegeneration With Brain Iron Accumulation (NBIA)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT00907283
Recruitment Status : Recruiting
First Posted : May 22, 2009
Last Update Posted : August 4, 2022
Information provided by (Responsible Party):
Dr. Gian Luca Forni, Ente Ospedaliero Ospedali Galliera

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Neurodegenerative Disease Iron Overload Drug: Deferiprone Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Ferrochelating Treatment in Patients Affected by "Neurodegeneration With Brain Iron Accumulation" (NBIA)
Study Start Date : November 2008
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : December 2024

Arm Intervention/treatment
Experimental: deferiprone
15 mg/Kg/twice for 1 year
Drug: Deferiprone
15 mg/Kg/twice for 1 year
Other Names:
  • EU/1/99/108/002 Ferriprox 100 mg/ml Oral solution
  • EU/1/99/108/003 Ferriprox 100 mg/ml Oral solution

Primary Outcome Measures :
  1. 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).

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   1 Year to 80 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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.

Exclusion criteria:

  • 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.

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 identifier (NCT number): NCT00907283

Layout table for location contacts
Contact: Gian Luca Forni, MD 0039 010563 ext 4557
Contact: Silvia Caviglia 0039 010563 ext 4557

Layout table for location information
Neurological Pathology Department, Brotzu Hospital Active, not recruiting
Cagliari, Italy, 09134
Centre of Microcitemia and Congenital Anemias, Galliera Hospital Recruiting
Genoa, Italy, 16128
Principal Investigator: Gian Luca Forni, MD         
Clinic of Neurology, University of Genoa Active, not recruiting
Genoa, Italy, 16132
Sponsors and Collaborators
Ente Ospedaliero Ospedali Galliera
Layout table for investigator information
Principal Investigator: Gian Luca Forni, MD E.O. Ospedali Galliera. Centro della Microcitemia e delle Anemie Congenite -Ematology - Genoa Italy
Publications of Results:
Other Publications:
Layout table for additonal information
Responsible Party: Dr. Gian Luca Forni, MD, Ente Ospedaliero Ospedali Galliera Identifier: NCT00907283    
Other Study ID Numbers: Deferiprone08
EUDRACT NUMBER 2008-005206-39
First Posted: May 22, 2009    Key Record Dates
Last Update Posted: August 4, 2022
Last Verified: August 2022
Keywords provided by Dr. Gian Luca Forni, Ente Ospedaliero Ospedali Galliera:
Iron overload AND brain
Iron chelation AND neurodegeneration
Brain iron Overload
Brain iron Accumulation
Additional relevant MeSH terms:
Layout table for MeSH terms
Neurodegenerative Diseases
Pantothenate Kinase-Associated Neurodegeneration
Iron Overload
Nerve Degeneration
Iron Metabolism Disorders
Metabolic Diseases
Nervous System Diseases
Pathologic Processes
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Neuroaxonal Dystrophies
Movement Disorders
Heredodegenerative Disorders, Nervous System
Genetic Diseases, Inborn
Pharmaceutical Solutions
Iron Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action