ARTEMIS: UC-MSCs After Mechanical Thrombectomy for Acute Ischemic Stroke (ARTEMIS)
ARTEMIS: Safety and Feasibility of Intra-arterial Administration of Allogeneic Umbilical Cord-Derived Mesenchymal Stromal Cells (UC-MSCs) After Mechanical Thrombectomy in Acute Ischemic Stroke - A Phase I Controlled Trial
This study will evaluate the safety and feasibility of administering umbilical cord-derived mesenchymal stromal cells (UC-MSCs) following mechanical thrombectomy in adults with acute ischemic stroke. Acute ischemic stroke occurs when a blood clot blocks blood flow to part of the brain, potentially causing brain tissue damage and neurological impairment.
The study will include 10 adults aged 18 to 70 years. All participants will receive standard stroke care, including mechanical thrombectomy to remove the blood clot. Participants will be randomly assigned to one of two groups.
One group will receive standard care plus a single dose of 20 million UC-MSCs derived from donated umbilical cord tissue. The cells will be delivered through a microcatheter into the artery supplying the affected part of the brain. The other group will receive standard care without the cell treatment. Both groups will receive physical rehabilitation.
Researchers will follow participants for six months. They will monitor health problems and assess recovery, disability, blood markers, and brain scans. The main goal is to determine whether this treatment can be administered safely and feasibly. It is not yet known whether the treatment will improve recovery after stroke.
Aperçu de l'étude
Statut
Les conditions
Description détaillée
- Scientific Rationale: Acute ischemic stroke results from an interruption of cerebral blood flow, causing ischemic injury and potentially persistent neurological disability. Mechanical thrombectomy restores blood flow by removing the occluding thrombus; however, successful reperfusion does not necessarily prevent secondary tissue injury or subsequent neurological impairment. Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) possess immunomodulatory and tissue-repair properties that provide a scientific rationale for investigating their therapeutic potential following ischemic stroke. The safety and feasibility of intra-arterial administration after mechanical thrombectomy during the acute phase require further clinical evaluation.
- Study Overview and Procedures:
ARTEMIS (ARterial ThErapy with Mesenchymal stromal cells In Stroke) is a Phase 1 randomized, controlled clinical trial evaluating the safety and feasibility of intra-arterial administration of allogeneic UC-MSCs following mechanical thrombectomy. The study will include ten adults aged 18-70 years with imaging-confirmed acute ischemic stroke, a National Institutes of Health Stroke Scale (NIHSS) score of 6-20, and a prestroke modified Rankin Scale (mRS) score below 2. Participants must be eligible for mechanical thrombectomy within six hours of symptom onset and achieve successful reperfusion, defined as a modified Thrombolysis in Cerebral Infarction (mTICI) grade of 2b-3. Key exclusions include previous stroke, cerebellar or brainstem stroke, intracranial hemorrhage or major structural brain lesions, significant coagulation disorders, severe uncontrolled comorbidities, recent myocardial infarction, seizures, cancer, pregnancy or breastfeeding, contrast-agent allergy, and conditions that prevent informed participation or reliable follow-up. Written informed consent will be obtained from participants or their legally authorized representatives.
Participants will be randomly allocated in a 1:1 ratio to receive standard stroke care alone or standard care supplemented with cell administration. The randomization sequence will be generated using the Sealed Envelope platform, as specified in the study protocol.
In the intervention group, cell administration will take place after angiographic confirmation of successful reperfusion. The cells will be delivered through a microcatheter into the main artery supplying the infarcted territory. Repeat angiography will be performed after administration to assess for vascular occlusion or hemorrhage. Both groups will receive routine post-thrombectomy care and physical rehabilitation.
- Investigational Product:
The allogeneic UC-MSC product, called Whartocell®, is manufactured under Good Manufacturing Practice (GMP) conditions and has approval for cerebral palsy (CP) and osteoarthritis indications.
The investigational product consists of allogeneic mesenchymal stromal cells isolated from Wharton's jelly tissue obtained from donated full-term umbilical cords following the required consent procedures. Umbilical cord tissue will be collected under sterile conditions and processed to isolate the stromal cell population and will undergo product characterization and quality-control testing.
- Safety Monitoring:
Participants will undergo clinical monitoring throughout the study and follow-up period. Adverse events will be documented and evaluated for severity, duration, and potential relationship to the investigational product or study procedures. The protocol specifies the use of the Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE v5.0), for safety monitoring.
Serious adverse events and suspected unexpected serious adverse reactions will be managed and reported according to the study protocol and applicable institutional requirements. Safety information will be reviewed by the clinical team and the Data and Safety Monitoring Board (DSMB), as specified in the protocol.
- Study Objectives:
This early-phase clinical investigation aims to establish preliminary evidence regarding the safety and feasibility of intra-arterial UC-MSC administration following mechanical thrombectomy during the acute phase of stroke. The findings may inform the design of subsequent clinical studies evaluating cell-based interventions for acute ischemic stroke. The study is exploratory and is not intended to establish definitive therapeutic efficacy.
Type d'étude
Inscription (Estimé)
Phase
- La phase 1
Contacts et emplacements
Coordonnées de l'étude
- Nom: Elaheh Khodadoust, MD-MPH
- Numéro de téléphone: +989121216987
- E-mail: elaheh.khodadoust@gmail.com
Sauvegarde des contacts de l'étude
- Nom: Masoumeh Nouri, PhD
- Numéro de téléphone: +989129582158201
- E-mail: mnouritra@gmail.com
Lieux d'étude
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Tehran Province
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Tehran, Tehran Province, L'Iran, 1593748711
- Firoozgar hospital
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Contact:
- Supervisor of Interventional Cath Lab
- Numéro de téléphone: 02182141000
- E-mail: dr.f.ebrahimnia@gmail.com
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
- Age 18 to 70 years;
- Acute ischemic stroke diagnosed clinically;
- Acute ischemic stroke confirmed by CT or MRI;
- Eligible for mechanical thrombectomy that can be performed within six hours of symptom onset;
- NIHSS score from 6 to 20;
- Pre-stroke modified Rankin Scale (mRS) score less than 2;
- Successful reperfusion (mTICI 2b or 3) on angiography after thrombectomy;
- Written informed consent from the patient or a legally authorized representative.
Exclusion Criteria:
- Previous stroke;
- Infarct in the cerebellum or brainstem;
- Small lacunar infarct (lesion smaller than 15-20 mm);
- Subarachnoid, intraventricular, or intracerebral hemorrhage, or a structural brain lesion such as a tumor, on CT or MRI;
- Midline shift, cerebral edema, or an infarct in an inaccessible location on CT or MRI;
- Candidate for decompressive craniectomy;
- Known coagulation or hematologic disorder (e.g., aplastic anemia) or current anticoagulant use (e.g., warfarin);
- Uncontrolled blood glucose;
- Known hepatic, renal, or heart failure;
- Myocardial infarction within the past 6 months;
- History of seizures within the past 6 months;
- History of cancer;
- Known intellectual, cognitive (e.g., dementia) or psychiatric disorder that would impair understanding of, or adherence to, study procedures and follow-up;
- Pregnancy or breastfeeding;
- Allergy to contrast media.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Expérimental: Allogeneic UC-MSCs Plus Standard Care
Participants in the experimental group will receive standard emergency care for acute ischemic stroke, including mechanical thrombectomy. Following successful thrombectomy and angiographic confirmation of reperfusion, a single dose of 20 × 10⁶ allogeneic umbilical cord-derived mesenchymal stromal cells is administered intra-arterially into the artery supplying the infarcted territory during the same procedure. Thereafter, participants will receive routine post-stroke care and physical rehabilitation. |
Allogeneic mesenchymal stromal cells derived from Wharton's jelly of donated full-term umbilical cords. A single dose of 20 × 10⁶ cells suspended in 20 mL of normal saline is administered through a microcatheter into the artery supplying the infarcted area following successful reperfusion after mechanical thrombectomy. Standard emergency care for acute ischemic stroke, including mechanical thrombectomy to remove the occluding blood clot, followed by routine post-thrombectomy care and physical rehabilitation according to the study protocol. |
|
Comparateur actif: Standard Care Alone
Participants in the control group will receive standard emergency care for acute ischemic stroke, including mechanical thrombectomy performed using the same procedural approach as in the experimental group. Following thrombectomy, participants will receive routine post-stroke care and physical rehabilitation. No cell infusion will be administered. |
Standard emergency care for acute ischemic stroke, including mechanical thrombectomy to remove the occluding blood clot, followed by routine post-thrombectomy care and physical rehabilitation according to the study protocol. |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Incidence of Serious Adverse Events (SAEs)
Délai: During the intervention and 1 hour, 24 hours, 3 days, 7 days, 1 month, 3 months, and 6 months after the intervention
|
Number of participants experiencing one or more serious adverse events during follow-up, including events resulting in death, life-threatening conditions, prolonged hospitalization, persistent or significant disability, or requiring medical or surgical intervention to prevent such outcomes. Event severity and relationship to the study intervention will be assessed by the clinical team. |
During the intervention and 1 hour, 24 hours, 3 days, 7 days, 1 month, 3 months, and 6 months after the intervention
|
|
Incidence of Adverse Events (AEs)
Délai: During the intervention and 1 hour, 24 hours, 3 days, 7 days, 1 month, 3 months, and 6 months after the intervention.
|
The frequency, type, severity, and relatedness of adverse events associated with intra-arterial infusion of allogeneic umbilical cord-derived mesenchymal stromal cells after mechanical thrombectomy based on Common Terminology Criteria for Adverse Events (CTCAE) version 5. |
During the intervention and 1 hour, 24 hours, 3 days, 7 days, 1 month, 3 months, and 6 months after the intervention.
|
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Feasibility of Intra-Arterial UC-MSC Administration
Délai: During the intervention (Day 0)
|
Feasibility will be assessed by the proportion of participants assigned to the intervention group in whom the planned intra-arterial infusion of 20 × 10⁶ allogeneic UC-MSCs is successfully completed according to the study protocol. The number of successful and unsuccessful administrations will be recorded, together with reasons for any failure to initiate or complete the infusion. |
During the intervention (Day 0)
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Proportion of Participants with mRS 0-2
Délai: Baseline, 24 hours, 3 days, 7 days, 1, 3, and 6 months
|
Number and percentage of participants with a modified Rankin Scale (mRS) score of 0-2 in each study group, comparing the UC-MSC group with the control group. (mRS ranges from 0 (no symptoms) to 6 (death); higher scores mean greater disability) |
Baseline, 24 hours, 3 days, 7 days, 1, 3, and 6 months
|
|
Proportion of Participants with a Reduction in mRS Score Compared with the Initial Pre-Treatment Assessment
Délai: Baseline, 24 hours, 3 days, 7 days, 1, 3, and 6 months
|
Number and percentage of participants achieving a reduction in the modified Rankin Scale (mRS) score, compared between the intervention and control groups. (mRS ranges from 0 (no symptoms) to 6 (death); higher scores mean greater disability.) |
Baseline, 24 hours, 3 days, 7 days, 1, 3, and 6 months
|
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Change in National Institutes of Health Stroke Scale (NIHSS) from baseline
Délai: Baseline, 24 hours, 3 days, 7 days, 1, 3, and 6 months
|
Change from baseline in National Institutes of Health Stroke Scale score. NIHSS ranges from 0 to 42; higher scores mean more severe neurological deficit. |
Baseline, 24 hours, 3 days, 7 days, 1, 3, and 6 months
|
|
Change in Serum Brain-Derived Neurotrophic Factor (BDNF) Concentration
Délai: Baseline, 3 days, and 6 months after intervention.
|
Change in serum BDNF concentration from baseline, measured using the protocol-specified laboratory assay and compared between the intervention and control groups. |
Baseline, 3 days, and 6 months after intervention.
|
|
Change in Serum Matrix Metalloproteinase-9 (MMP-9) Concentration
Délai: Baseline, 3 days, and 6 months after intervention.
|
Change in serum MMP-9 concentration from baseline, measured using the protocol-specified laboratory assay and compared between the intervention and control groups. |
Baseline, 3 days, and 6 months after intervention.
|
|
Change in Serum S100B Concentration
Délai: Baseline, 3 days, and 6 months after intervention.
|
Change in serum S100B concentration from baseline, measured using the protocol-specified laboratory assay and compared between the intervention and control groups. |
Baseline, 3 days, and 6 months after intervention.
|
Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Changes in Cerebral Infarct Volume on CT/MRI
Délai: Initial presentation, 24 hours, and 6 months after intervention,
|
Cerebral infarct core volume will be assessed using brain imaging according to the study protocol. Imaging findings will be evaluated to characterize changes in the extent of cerebral injury during follow-up. |
Initial presentation, 24 hours, and 6 months after intervention,
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Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Dr. Massoud Vosough, MD-PhD, Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
- Chercheur principal: Dr. Feiz Ebrahimnia, MD, Neurovascular intervention, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Estimé)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- ARTEMIS405000020
- IRCT20260922071161N1 (Autre identifiant: Iranian Registry of Clinical Trials)
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Description du régime IPD
The decision to share individual participant data will be made after completion of the study. Data may be made available for non-commercial research purposes, including systematic reviews, meta-analyses, and the design of future clinical trials, upon submission of a written request and approval by the Principal Investigator.
Informations sur les médicaments et les dispositifs, documents d'étude
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