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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Ferrochelating Treatment in Patients Affected by "Neurodegeneration With Brain Iron Accumulation" (NBIA)

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 Summary:

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 tr
Sponsor: Ente Ospedaliero Ospedali Galliera

Current 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).


Original Primary Outcome: To evaluate the efficacy and safety of the chelator therapy with deferiprone on cerebral iron accumulations. The safety and tolerability of the drug will be monitored by weekly monitoring of the CBC. [ Time Frame: 6 months + 6 months ]

Current Secondary Outcome:

Original Secondary Outcome:

Information By: Ente Ospedaliero Ospedali Galliera

Dates:
Date Received: May 21, 2009
Date Started: November 2008
Date Completion: December 2015
Last Updated: August 3, 2015
Last Verified: August 2015