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Perinatal Arterial Stroke Treated With Stromal Cells Intranasally (PASSIoN)

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ClinicalTrials.gov Identifier: NCT03356821
Recruitment Status : Not yet recruiting
First Posted : November 29, 2017
Last Update Posted : May 7, 2019
Sponsor:
Collaborators:
ZonMw: The Netherlands Organisation for Health Research and Development
M.D. Anderson Cancer Center
The University of Texas Health Science Center at San Antonio
Information provided by (Responsible Party):
Linda de Vries, MD, PhD, UMC Utrecht

Brief Summary:
This study will assess safety and feasibility of bone marrow-derived allogeneic MSCs, administered by the nasal route, in neonates who suffered from PAIS.

Condition or disease Intervention/treatment Phase
Perinatal Arterial Ischemic Stroke Neonatal Stroke Biological: Mesenchymal Stem Cells Phase 1 Phase 2

Detailed Description:
Perinatal arterial ischemic stroke (PAIS) is an important perinatal cause of long-lasting neurodevelopmental problems. Recent studies report an incidence of PAIS of 1 per 2300 full-term infants born alive. Adverse consequences of PAIS include hemiplegia, cognitive dysfunction, epilepsy and speech problems. In 50-75% of infants, neonatal stroke leads to abnormal neuromotor and -developmental outcome or epilepsy. The estimated annual mortality rate of neonatal stroke is 3.49/100,000 annually. Current treatment options for PAIS mainly focus on controlling convulsions and associated infections. There is no treatment available that leads to reduction of neonatal brain damage in this severely affected group of infants. This leads to life-long consequences of PAIS and forms a large burden for patients and society. The overall aim of this project is to meet this need by developing a cell based treatment strategy. Animal models of neonatal brain injury provide evidence for the feasibility and efficacy of intranasal mesenchymal stromal cell (MSC) application in the treatment of PAIS. Additionally, results from human trials with MSCs in the treatment of adult stroke or other pathologic conditions provide evidence that MSC treatment is safe. This project aims at making the first step towards clinical application of MSCs to treat PAIS. Successful completion of this project will provide the first evidence of the safety and feasibility of MSCs to treat brain damage in newborn infants. This study will assess safety and feasibility of bone marrow-derived allogeneic MSCs, administered by the nasal route, in neonates who suffered from PAIS.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Intervention Model Description: A phase I/II, open-label, single-arm, single-center intervention study in the NICU at the Wilhelmina children's Hospital / University Medical Centre in Utrecht of (near-)term newborns ≥36 weeks of gestation within the first week of onset of presenting clinical symptoms.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Adult Mesenchymal Stromal Cells to Regenerate the Neonatal Brain: the PASSIoN Trial (Perinatal Arterial Stroke Treated With Stromal Cells IntraNasally)
Estimated Study Start Date : August 2019
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Mesenchymal Stem Cells
All (near-)term newborns ≥36 weeks of gestation with or without clinical symptoms of PAIS but with a magnetic resonance imaging (MRI) confirmed PAIS (in the Middle Cerebral Artery region) will be eligible for this study. Following written parental consent, 10 patients will be included in our study.
Biological: Mesenchymal Stem Cells
One dose of 50x10^6 bone marrow-derived allogeneic MSCs via the nasal route as soon as possible after confirmation of the stroke (in the middle cerebral artery), but within the first week of onset of presenting clinical symptoms. Within 30 minutes after cleaning the nose with saline, using standard procedures operative at the Neonatal Intensive Care Unit, the MSC will be delivered.
Other Name: Bone Marrow-derived Allogeneic Mesenchymal Cells




Primary Outcome Measures :
  1. Incidence of adverse events related to intranasal MSC treatment (safety and tolerability) in the acute setting. [ Time Frame: 24 hours after treatment ]
    The primary objective is to determine if MSC treatment in neonates with PAIS is safe and tolerable in the acute setting. This will be measured by the incidence of treatment-related adverse events after MSC treatment.


Secondary Outcome Measures :
  1. Incidence of adverse events related to intranasal MSC treatment (safety and tolerability) in the subacute/long-term setting [ Time Frame: 3 months postnatal age ]
    The secondary objective is to determine subacute and long-term safety of MSC treatment at 3 months. This will be measured by the occurence of treatment-related adverse events, such as infections or cerebral tumorigenicity on MRI. Follow-up assessment at 3 months is part of regular care for neonates with PAIS.



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Ages Eligible for Study:   up to 10 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • (Near-)Term infants, ≥36+0 weeks of gestation, admitted to one of the Dutch Neonatal Intensive Care Units, diagnosed with PAIS, confirmed by MRI within 3 days after presentation with clinical symptoms.
  • PAIS as characterized by a predominantly unilateral ischemic lesion within the territory of the middle cerebral artery, with involvement of the corticospinal tracts, cortex, white matter and basal ganglia.
  • Written informed consent from custodial parent(s).

Exclusion Criteria:

  • Any proven or suspected congenital anomaly, chromosomal disorder, metabolic disorder.
  • Presence of an infection of the central nervous system.
  • No realistic prospect of survival, (e.g. severe brain injury), at the discretion of the attending physician.

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): NCT03356821


Contacts
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Contact: Linda S. de Vries, MD, PhD +31(0)887554545 l.s.devries@umcutrecht.nl
Contact: Nienke Wagenaar, MD +31(0)887554545 ext 63630 n.wagenaar@umcutrecht.nl

Locations
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Netherlands
Wilhelmina Childrens Hostpital/University Medical Center Utrecht
Utrecht, Netherlands, 3584 EA
Sponsors and Collaborators
UMC Utrecht
ZonMw: The Netherlands Organisation for Health Research and Development
M.D. Anderson Cancer Center
The University of Texas Health Science Center at San Antonio
Investigators
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Principal Investigator: Linda S. de Vries, MD, PhD UMC Utrecht
Principal Investigator: Manon Benders, MD, PhD UMC Utrecht
Principal Investigator: Floris Groenendaal, MD, PhD UMC Utrecht
Principal Investigator: Frank van Bel, MD, PhD UMC Utrecht

Publications:

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Responsible Party: Linda de Vries, MD, PhD, MD, PhD, UMC Utrecht
ClinicalTrials.gov Identifier: NCT03356821     History of Changes
Other Study ID Numbers: NL59265.000.16
First Posted: November 29, 2017    Key Record Dates
Last Update Posted: May 7, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Stroke
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases