The alteration of iron metabolism is reported in animal models of amyotrophic lateral sclerosis (ALS) as well as in sporadic and genetic forms (SOD1 and C9orf72) of ALS. The high iron concentration of the brain, due to its high energy demand (high oxygen consumption), makes motor neurons particularly vulnerable to energy deficit and oxidative stress. Post-mortem examinations and MRI scans in patients with ALS have found signs of iron accumulation in the central motor tract; and a high level of serum ferritin, which is a marker of iron levels, is associated with a lower prognosis. In ALS mouse models, the use of iron chelators has demonstrated neuroprotection and increased life expectancy, suggesting that elimination of excess iron from the brain can prevent neuronal loss and, consequently, a slow progression of the disease. Conservative chelation of iron refers to a modality whereby much of the iron that binds to the chelator is redistributed in the body rather than exhausted. Using a chelator, deferiprone, with this feature, in a safety pilot study, a very good safety profile was observed. Deferiprone eliminated excess iron from brain regions, reduced oxidative damage and cell death associated with regional iron deposits with no apparent negative impact on the iron levels needed. Now, the efficacy of this new therapeutic modality of neuroprotection is being evaluated in a randomized, double-blind, placebo-controlled, multicenter study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
372
One 600 mg delayed-release tablets of deferiprone twice a day, for at 30 mg/kg/day
the placebo twice daily morning and evening.
Chr Angers
Angers, France
Chru Brest
Brest, France
Hopital Pierre Wertheimer - Hcl - Bron
Bron, France
Chu Cote de Nacre - Caen
Caen, France
Chu de Clermont-Ferrand
Clermont-Ferrand, France
Hôpital Roger Salengro, CHU
Lille, France
C H U Dupuytren Limoges
Limoges, France
Aphm Hopital La Timone
Marseille, France
Chu de Nancy
Nancy, France
Chu de Nice Hopital Pasteur
Nice, France
...and 5 more locations
CAFS score (Combined Assessment of Function and Survival)
CAFS score based on changes in amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) total scores and time to death from baseline (randomization visit) to 12 months
Time frame: at 12 months
Changes in ALS Functional Rating Scale-Revised (ALSFRS-R) total score
Time frame: Baseline, at 12 months
All-cause and respiratory insufficiency mortality
Time to death for all cause or respiratory insufficiency (defined as tracheostomy or the use of non-invasive ventilation for ≥ 23 h per day for 14 consecutive days) from baseline until 12 month
Time frame: at 12 months
Changes in muscle strength
Muscle strength measurements are determined by the overall mega-score for handheld dynamometry and manual muscular testing with a validated medical device provided
Time frame: Baseline, at 12 months
Change in the slow vital capacity
The slow vital capacity is measure by the maximum amount of air that can be exhaled following a deep breath. Reflecting the Respiratory insufficiency.
Time frame: Baseline, at 12 months
Changes in body weight
Time frame: Baseline, at 12 months
Change in Quality of life
Quality of life assessed using the five-item form of the ALS assessment questionnaire (ALSAQ-5) from baseline to 12 months
Time frame: Baseline, at 12 months
DSMIV criteria
Dementia (yes/no)
Time frame: at 12 months
Fronto-Temporal Dementia (FTD) criteria
Using the revised guidelines for the diagnosis of behavioral variant frontotemporal dementia based on recent literature and collective experience by Rascovsky K et al 2011; Lamarre AK et al 2013
Time frame: at 12 months
Change in Montreal Cognitive Assessment (MoCA)
MoCA evaluated of mild cognitive dysfunction.
Time frame: Baseline, at 12 months
Change in Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen (ECAS)
ECAS determine cognitive and behavioral changes of patients suffering from Amyotrophic Lateral Sclerosis. With ECAS, ALS-specific (fluency, executive functions and social cognition, language) and ALS-nonspecific (memory, visuospatial functions) functions can be analyzed to enable the distinction from other diseases with cognitive and behavioral impairments.
Time frame: Baseline, at 12 months
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