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

NCT ID: NCT00907283

Last Updated: 2023-02-09

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-11-30
• Study Completion Date: 2024-12-31

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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

deferiprone

15 mg/Kg/twice for 1 year

Group Type: EXPERIMENTAL

Deferiprone

Intervention Type: DRUG

15 mg/Kg/twice for 1 year

Interventions

Deferiprone

15 mg/Kg/twice for 1 year

Intervention Type: DRUG

Other Intervention Names

EU/1/99/108/002 Ferriprox 100 mg/ml Oral solution; EU/1/99/108/003 Ferriprox 100 mg/ml Oral solution

Eligibility Criteria

Inclusion Criteria

• 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.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ente Ospedaliero Ospedali Galliera

OTHER

Sponsor Role: lead

Responsible Party

Dr. Gian Luca Forni

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gian Luca Forni, MD

Role: PRINCIPAL_INVESTIGATOR

E.O. Ospedali Galliera. Centro della Microcitemia e delle Anemie Congenite -Ematology - Genoa Italy

Locations

Neurological Pathology Department, Brotzu Hospital

Cagliari, , Italy

Centre of Microcitemia and Congenital Anemias, Galliera Hospital

Genoa, , Italy

Clinic of Neurology, University of Genoa

Genoa, , Italy

Countries

Italy

References

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.

Reference Type: BACKGROUND

PMID: 18383118 (View on PubMed)

Abbruzzese 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.

Reference Type: RESULT

PMID: 21791473 (View on PubMed)

Other Identifiers

EUDRACT NUMBER 2008-005206-39

Identifier Type: -

Identifier Source: secondary_id

Deferiprone08

Identifier Type: -

Identifier Source: org_study_id