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Trial record 2 of 7 for:    Neurodegeneration with Brain Iron Accumulation (NBIA)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00907283
Recruitment Status : Unknown
Verified August 2015 by Dr. Gian Luca Forni, Ente Ospedaliero Ospedali Galliera.
Recruitment status was:  Active, not recruiting
First Posted : May 22, 2009
Last Update Posted : August 5, 2015
Sponsor:
Information provided by (Responsible Party):
Dr. Gian Luca Forni, Ente Ospedaliero Ospedali Galliera

Tracking Information
First Submitted Date  ICMJE May 21, 2009
First Posted Date  ICMJE May 22, 2009
Last Update Posted Date August 5, 2015
Study Start Date  ICMJE November 2008
Estimated Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 9, 2013)
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upper limit of normal or if the neutrophil counts decrease to less than 1.5 x 109/L (1500 cells/µl) the Patient will be withdrawn from the study.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 Measures  ICMJE
 (submitted: May 21, 2009)
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 ]
Change History Complete list of historical versions of study NCT00907283 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ferrochelating Treatment in Patients Affected by Neurodegeneration With Brain Iron Accumulation (NBIA)
Official Title  ICMJE 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 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Neurodegenerative Disease
  • Iron Overload
Intervention  ICMJE 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
Study Arms  ICMJE Experimental: deferiprone
15 mg/Kg/twice for 1 year
Intervention: Drug: Deferiprone
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: May 21, 2009)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2015
Estimated Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 80 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00907283
Other Study ID Numbers  ICMJE Deferiprone08
EUDRACT NUMBER 2008-005206-39
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Dr. Gian Luca Forni, Ente Ospedaliero Ospedali Galliera
Study Sponsor  ICMJE Ente Ospedaliero Ospedali Galliera
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Gian Luca Forni, MD E.O. Ospedali Galliera. Centro della Microcitemia e delle Anemie Congenite -Ematology - Genoa Italy
PRS Account Ente Ospedaliero Ospedali Galliera
Verification Date August 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP