Clinical trial NCT05111821: Iron Chelation in the Prevention of Secondary Degeneration After Stroke
Official title: Long-term Iron Chelation in the Prevention of Secondary Remote Degeneration After Stroke
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Stroke
Keywords: Stroke
Deferiprone
Iron accumulation
Magnetic Resonance Imaging
Neuroprotective treatment
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2021-11-08
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Stroke is a major cause of disability over the world. While acute therapies have made huge progresses, the number of survivors leaving with clinical consequences of stroke is increasing. Beyond stroke itself, secondary neurodegeneration of disconnected areas, especially of central hubs such as the substantia nigra or the thalamus, could significantly impact the overall outcome of the patients. Data have identified iron accumulation within the disconnected areas as potentially accelerating neurodegeneration. In this research, the main objective is test whether long-term chelation through Deferiprone (Ferrirpox®, Chiesi) administered daily from 3-to-5 days following stroke to 6 months could avoid iron accumulation as measured with Magnetic resonance imaging (MRI) within disconnected areas (substantia nigra).

MRI imaging methods such as the quantification of the transverse relaxation rate R2\* provide highly correlated information to the histologically measured iron load


Eligibility criteria: Inclusion Criteria:

* Patient older than 18 years old.
* Covered by a social insurance
* With a stroke involving the deep territory of the middle cerebral artery (including at least half of the volume of the striatum) due to occlusion of the carotid artery or of proximal M1 or M2 segments. The artery can be occluded when the patient is admitted at the acute phase or already recanalized as soon as the striatum is involved.
* Absolute neutrophil count ≥1.5 x109/L.
* For women of childbearing potential, negative β HCG test and highly effective contraception (oestroprogestative contraception, intra-uterine device, bilateral salpingectomy) to be continued 6 months after the last administration of deferiprone.
* Men whose partner provides a highly effective contraception or who accept to use a contraception method (condom) while treated by deferiprone and to continue 90 days after the last administration of deferiprone
* Written informed consent dated and signed prior to the beginning of any procedures related to the clinical trial. Patients unable to give their personal consent (severe aphasia, impaired understanding or attention induced by the infarction) may be included with the consent by a trusted person provided in article L. 1111-6, by the family or by a person who has a close and stable relationship with the person concerned. The person concerned is informed as soon as possible and his consent is sought during visit at 3 month or 6 month if he regains his capacity to consent. These patients may be included because the treatment may be provided by the caregiver, or a home nurse for patients alone or for whom the caregiver is unable to follow the treatment. Most severe patients, in rehabilitation structure will have support for taking treatment and monitoring it

Exclusion Criteria:

* Contraindication to MRI.
* Pregnant or breast feeding women.
* Inability to swallow correctly (required for oral treatment).
* History of symptomatic cerebral infarct or hemorrhage.
* Pre-stroke modified Rankin Scale \[mRS\] score\>2).
* History of severe cognitive impairment (dementia).
* History of recent (within the past 6 months) and evolving psychiatric disorders matching to axis 1 of the DSM-IV criteria.
* History of stroke directly involving substantia nigra or thalamus.
* Microbleed, or past hematoma involving substantia nigra; past hematoma involving thalamus.
* PH1 or PH2 hemorrhagic transformation.
* Hypersensitivity to Deferiprone or any of the excipients mentioned in section 6.1 of the Summary of Product characteristics of Ferriprox
* Patients with agranulocytosis or with a history of agranulocytosis.
* Patients with history of relapsing neutropenia.
* Patient with immunosuppression condition.
* Due to the risk of agranulocytosis caused by Deferiprone and the unknown mechanism by which this agranulocytosis is induced, combining Deferiprone with other medicinal products known to cause agranulocytosis will not be allowed. Such medicinal products include clozapine as well as some NSAIDs (e.g. Phenylbutazone or Metamizole), antithyroid agents, sulfonamide antibiotics or metothrexate.
* Patients with anaemia (regardless of latter aetiology) or a history of another haematological disease.
* Participation in another drug study (Investigational medical product) within 1 month prior to inclusion in the study.
* Kidney or liver failure.
* Patient in an emergency situation
* Patient under permanent guardianship.
* Patient subject to a safeguard measure of justice

Primary outcomes:
measure: R2* Index within the homolateral black substance
timeFrame: Day 1
measure: R2* Index within the homolateral black substance
timeFrame: 6 Month
Secondary outcomes:
measure: R2* Index within the thalamus and the middle nucleus of the homolateral thalamus
timeFrame: Day 1
measure: R2* Index within the thalamus and the middle nucleus of the homolateral thalamus
timeFrame: 6 Month
measure: R2* Relaxivity values
timeFrame: Day 1
measure: R2* Relaxivity values
timeFrame: 6 Month
measure: Fugl-Meyer Score
timeFrame: Day 1
measure: Fugl-Meyer Score
timeFrame: 3 Month
measure: Fugl-Meyer Score
timeFrame: 6 Month
measure: Box and Block test Score
timeFrame: Day 1
measure: Box and Block test Score
timeFrame: 3 Month
measure: Box and Block test Score
timeFrame: 6 Month
measure: Modified Rankin scale Score
timeFrame: Day 1
measure: Modified Rankin scale Score
timeFrame: 3 Month
measure: Modified Rankin scale Score
timeFrame: 6 Month
measure: Montreal cognitive assessment (MoCA) Score
timeFrame: Day 1
measure: Montreal cognitive assessment (MoCA) Score
timeFrame: 3 Month
measure: Montreal cognitive assessment (MoCA) Score
timeFrame: 6 Month
measure: Center for epidemiologic studies depression scale (CES-D)
timeFrame: Day 1
measure: Center for epidemiologic studies depression scale (CES-D)
timeFrame: 3 Month
measure: Center for epidemiologic studies depression scale (CES-D)
timeFrame: 6 Month
measure: Generalized anxiety disorder scale (GAD-7) scale
timeFrame: Day 1
measure: Generalized anxiety disorder scale (GAD-7) scale
timeFrame: 3 Month
measure: Generalized anxiety disorder scale (GAD-7) scale
timeFrame: 6 Month
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU Bordeaux
city: Lille
country: France
facility: CHU de Lille
city: Montpellier
country: France
facility: CHU de Montpellier
Study officials:
affiliation: University Hospital, Bordeaux
name: Thomas TOURDIAS
role: STUDY_DIRECTOR
References: