Perinatal Arterial Stroke Treated With Stromal Cells Intranasally (PASSIoN)

October 6, 2021 updated by: dr. M.J.N.L. Benders, UMC Utrecht

Adult Mesenchymal Stromal Cells to Regenerate the Neonatal Brain: the PASSIoN Trial (Perinatal Arterial Stroke Treated With Stromal Cells IntraNasally)

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Utrecht, Netherlands, 3584 EA
        • Wilhelmina Childrens Hostpital/University Medical Center Utrecht

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 1 week (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • Bone Marrow-derived Allogeneic Mesenchymal Cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
24 hours after treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
3 months postnatal age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

UMC Utrecht

Collaborators

M.D. Anderson Cancer Center
The University of Texas Health Science Center at San Antonio
ZonMw: The Netherlands Organisation for Health Research and Development

Investigators

  • 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
  • Principal Investigator: Cora Nijboer, PhD, UMC Utrecht

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 11, 2020

Primary Completion (Actual)

July 27, 2021

Study Completion (Actual)

July 27, 2021

Study Registration Dates

First Submitted

November 8, 2017

First Submitted That Met QC Criteria

November 22, 2017

First Posted (Actual)

November 29, 2017

Study Record Updates

Last Update Posted (Actual)

October 7, 2021

Last Update Submitted That Met QC Criteria

October 6, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL59265.000.16

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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