Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 25 of 677 for:    amyotrophic lateral sclerosis

Conservative Iron Chelation as a Disease-modifying Strategy in Amyotrophic Lateral Sclerosis (FAIR-ALS II)

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.
 
ClinicalTrials.gov Identifier: NCT03293069
Recruitment Status : Recruiting
First Posted : September 26, 2017
Last Update Posted : May 21, 2019
Sponsor:
Collaborator:
Ministry of Health, France
Information provided by (Responsible Party):
University Hospital, Lille

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis Drug: Deferiprone Drug: Placebo Oral Tablet Phase 2 Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 240 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Conservative Iron Chelation as a Disease-modifying Strategy in Amyotrophic Lateral Sclerosis: Multicentre, Parallel-group, Placebo-controlled, Randomized Clinical Trial of Deferiprone
Actual Study Start Date : January 30, 2019
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : April 2022


Arm Intervention/treatment
Experimental: Deferiprone
Half of participants will receive twice-daily oral deferiprone taken over 12 months.
Drug: Deferiprone
One 600 mg delayed-release tablets of deferiprone twice a day, for at 30 mg/kg/day
Other Name: DFP

Placebo Comparator: Placebo
Half of participants will receive the placebo Twice-daily oral placebo taken over 12 months
Drug: Placebo Oral Tablet
the placebo twice daily morning and evening.




Primary Outcome Measures :
  1. CAFS score (Combined Assessment of Function and Survival) [ Time Frame: at 12 months ]
    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


Secondary Outcome Measures :
  1. Changes in ALS Functional Rating Scale-Revised (ALSFRS-R) total score [ Time Frame: Baseline, at 12 months ]
  2. All-cause and respiratory insufficiency mortality [ Time Frame: at 12 months ]
    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

  3. Changes in muscle strength [ Time Frame: Baseline, at 12 months ]
    Muscle strength measurements are determined by the overall mega-score for handheld dynamometry and manual muscular testing with a validated medical device provided

  4. Change in the slow vital capacity [ Time Frame: Baseline, at 12 months ]
    The slow vital capacity is measure by the maximum amount of air that can be exhaled following a deep breath. Reflecting the Respiratory insufficiency.

  5. Changes in body weight [ Time Frame: Baseline, at 12 months ]
  6. Change in Quality of life [ Time Frame: Baseline, at 12 months ]
    Quality of life assessed using the five-item form of the ALS assessment questionnaire (ALSAQ-5) from baseline to 12 months

  7. DSMIV criteria [ Time Frame: at 12 months ]
    Dementia (yes/no)

  8. Fronto-Temporal Dementia (FTD) criteria [ Time Frame: at 12 months ]
    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

  9. Change in Montreal Cognitive Assessment (MoCA) [ Time Frame: Baseline, at 12 months ]
    MoCA evaluated of mild cognitive dysfunction.

  10. Change in Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen (ECAS) [ Time Frame: Baseline, at 12 months ]

    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.




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:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Categorized as; possible, laboratory supported probable, probable, or definite ALS (revised El Escorial criteria)
  • Spinal and bulbar forms of ALS
  • Duration of the disease of less than 18 months since the first symptoms of motor deficit or amyotrophy (isolated cramps or fasciculation will not be considered).
  • Duration of the disease of less than 6 months since the diagnosis
  • A mild functional handicap score for ALSFRS-R ≥36
  • An upright slow vital capacity > 70% of the predicted value for age, height, and sex and an inspiratory pressure > 60 cm of H2O at screening (In case of a limit abnormal value, it will be recommended that patient re-assessment occurs three months later).
  • Able to swallow (required for oral treatment)

Exclusion Criteria:

  • Patients with high frequency of comorbidity or vital risks that may reasonably impair life expectancy
  • Progressing axis I psychiatric disorders (psychosis, hallucinations, substance addiction, bipolar disorder, severe depression, suicidal ideation), in accordance with the Diagnostic and Statistical Manual of Mental Disorders. Before entry into the study, exclusion or stabilization of conditions must occur for patients suffering from mild or moderate depressive episodes (not in remission) or severe and uncontrolled anxiety.
  • Dementia according to the Diagnostic and Statistical Manual of Mental Disorders
  • Exposure to any other experimental drug up to 30 days before day 1
  • If the patient is under riluzole, it has to be for at least 1 month (to rule out the principal risk of hepatitis; neutropenia is exceptional)
  • Due to the risk of agranulocytosis (estimated at 2%) caused by the Investigational Medicinal Products (IMPs) and the unknown mechanism by which this agranulocytosis is induced, combining Deferiprone with other medicinal products known to cause agranulocytosis (as described in the IB) will not be allowed. Such medicinal products include clozapine as well as some NSAIDs (e.g. Phenylbutazone or Metamizole), antithyroid agents, sulfonamide antibiotics or methotrexate.
  • A history of relapsing neutropenia
  • Patients with agranulocytosis or with a history of agranulocytosis.
  • Hypersensitivity to Deferiprone
  • Patients with anaemia (regardless of latter aetiology) or a history of another haematological disease. Haemochromatosis is not an exclusion criterion if controlled.
  • Pregnant or breastfeeding women or women of childbearing potential not taking highly effective contraception.
  • Kidney or liver failure.
  • Inability to provide informed consent.
  • Participation in another clinical trial within 1 month prior to inclusion in the study
  • Patients under trusteeship

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 ClinicalTrials.gov identifier (NCT number): NCT03293069


Contacts
Layout table for location contacts
Contact: David Devos, MD,PhD 3 20.44.41.45. ext +33 david.devos@chru-lille.fr

Locations
Layout table for location information
France
Hôpital Roger Salengro, CHU Recruiting
Lille, France, 59000
Contact: DAVID DEVOS    +33 320446243      
Contact: PAULINE GUYON    +33 320446711    pauline.guyon@chru-lille.fr   
Principal Investigator: David Devos, MD,PhD         
Sponsors and Collaborators
University Hospital, Lille
Ministry of Health, France
Investigators
Layout table for investigator information
Principal Investigator: David Devos, MD,PhD University Hospital, Lille

Layout table for additonal information
Responsible Party: University Hospital, Lille
ClinicalTrials.gov Identifier: NCT03293069     History of Changes
Other Study ID Numbers: 2016_76
2017-003763-35 ( EudraCT Number )
First Posted: September 26, 2017    Key Record Dates
Last Update Posted: May 21, 2019
Last Verified: May 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Lille:
Conservative Iron Chelation
Disease-modifying Strategy
Additional relevant MeSH terms:
Layout table for MeSH terms
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Deferiprone
Iron Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action