Perinatal Arterial Stroke Treated With Stromal Cells Intranasally

NCT03356821 | Completed Phase 1 Results DMC

• 1 other identifier: NL59265.000.16
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Perinatal Arterial Ischemic Stroke; Neonatal Stroke

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events Related to Intranasal MSC Treatment (Safety and Tolerability) in the Acute Setting.

  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 number of Participants with treatment-related adverse events after MSC treatment.

  24 hours after treatment

Secondary Outcomes (1)

• Number of Participants With Adverse Events Related to Intranasal MSC Treatment (Safety and Tolerability) in the Subacute/Long-term Setting

  3 months postnatal age

Study Arms (1)

Mesenchymal Stem Cells

EXPERIMENTAL

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

Interventions

Mesenchymal Stem Cells BIOLOGICAL

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.

Also known as: Bone Marrow-derived Allogeneic Mesenchymal Cells

Mesenchymal Stem Cells

Eligibility Criteria

• Age: Up to 10 Days
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• (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).

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

Wilhelmina Childrens Hostpital/University Medical Center Utrecht

Utrecht, 3584 EA, Netherlands

Location

Related Publications (14)

• Donega V, van Velthoven CT, Nijboer CH, Kavelaars A, Heijnen CJ. The endogenous regenerative capacity of the damaged newborn brain: boosting neurogenesis with mesenchymal stem cell treatment. J Cereb Blood Flow Metab. 2013 May;33(5):625-34. doi: 10.1038/jcbfm.2013.3. Epub 2013 Feb 13.

  PMID: 23403379 BACKGROUND

• Donega V, van Velthoven CT, Nijboer CH, van Bel F, Kas MJ, Kavelaars A, Heijnen CJ. Intranasal mesenchymal stem cell treatment for neonatal brain damage: long-term cognitive and sensorimotor improvement. PLoS One. 2013;8(1):e51253. doi: 10.1371/journal.pone.0051253. Epub 2013 Jan 3.

  PMID: 23300948 BACKGROUND

• Donega V, Nijboer CH, van Tilborg G, Dijkhuizen RM, Kavelaars A, Heijnen CJ. Intranasally administered mesenchymal stem cells promote a regenerative niche for repair of neonatal ischemic brain injury. Exp Neurol. 2014 Nov;261:53-64. doi: 10.1016/j.expneurol.2014.06.009. Epub 2014 Jun 16.

  PMID: 24945601 BACKGROUND

• Donega V, Nijboer CH, Braccioli L, Slaper-Cortenbach I, Kavelaars A, van Bel F, Heijnen CJ. Intranasal administration of human MSC for ischemic brain injury in the mouse: in vitro and in vivo neuroregenerative functions. PLoS One. 2014 Nov 14;9(11):e112339. doi: 10.1371/journal.pone.0112339. eCollection 2014.

  PMID: 25396420 BACKGROUND

• van Velthoven CT, Kavelaars A, Heijnen CJ. Mesenchymal stem cells as a treatment for neonatal ischemic brain damage. Pediatr Res. 2012 Apr;71(4 Pt 2):474-81. doi: 10.1038/pr.2011.64. Epub 2012 Feb 8.

  PMID: 22430383 BACKGROUND

• van Velthoven CT, Kavelaars A, van Bel F, Heijnen CJ. Mesenchymal stem cell transplantation changes the gene expression profile of the neonatal ischemic brain. Brain Behav Immun. 2011 Oct;25(7):1342-8. doi: 10.1016/j.bbi.2011.03.021. Epub 2011 Apr 5.

  PMID: 21473911 BACKGROUND

• van Velthoven CT, Kavelaars A, van Bel F, Heijnen CJ. Nasal administration of stem cells: a promising novel route to treat neonatal ischemic brain damage. Pediatr Res. 2010 Nov;68(5):419-22. doi: 10.1203/PDR.0b013e3181f1c289.

  PMID: 20639794 BACKGROUND

• van Velthoven CT, Kavelaars A, van Bel F, Heijnen CJ. Repeated mesenchymal stem cell treatment after neonatal hypoxia-ischemia has distinct effects on formation and maturation of new neurons and oligodendrocytes leading to restoration of damage, corticospinal motor tract activity, and sensorimotor function. J Neurosci. 2010 Jul 14;30(28):9603-11. doi: 10.1523/JNEUROSCI.1835-10.2010.

  PMID: 20631189 BACKGROUND

• van Velthoven CT, Kavelaars A, van Bel F, Heijnen CJ. Mesenchymal stem cell treatment after neonatal hypoxic-ischemic brain injury improves behavioral outcome and induces neuronal and oligodendrocyte regeneration. Brain Behav Immun. 2010 Mar;24(3):387-93. doi: 10.1016/j.bbi.2009.10.017. Epub 2009 Oct 31.

  PMID: 19883750 BACKGROUND

• van Velthoven CT, Kavelaars A, van Bel F, Heijnen CJ. Regeneration of the ischemic brain by engineered stem cells: fuelling endogenous repair processes. Brain Res Rev. 2009 Jun;61(1):1-13. doi: 10.1016/j.brainresrev.2009.03.003. Epub 2009 Apr 5.

  PMID: 19348860 BACKGROUND

• Wagenaar N, Nijboer CH, van Bel F. Repair of neonatal brain injury: bringing stem cell-based therapy into clinical practice. Dev Med Child Neurol. 2017 Oct;59(10):997-1003. doi: 10.1111/dmcn.13528. Epub 2017 Aug 8.

  PMID: 28786482 BACKGROUND

• Wagenaar N, de Theije CGM, de Vries LS, Groenendaal F, Benders MJNL, Nijboer CHA. Promoting neuroregeneration after perinatal arterial ischemic stroke: neurotrophic factors and mesenchymal stem cells. Pediatr Res. 2018 Jan;83(1-2):372-384. doi: 10.1038/pr.2017.243. Epub 2017 Nov 1.

  PMID: 28949952 BACKGROUND

• Wagenaar N, Baak LM, van der Aa NE, Groenendaal F, Dudink J, Tataranno ML, Koopman C, Verhage CH, Eijsermans RMJC, van Teeseling HC, Smit LS, Jellema RK, de Haan TR, Ter Horst HJ, de Boode WP, Steggerda SJ, Mulder-de Tollenaer SM, Dijkman KP, de Haar CG, de Vries LS, van Bel F, Heijnen CJ, Nijboer CH, Benders MJNL. Perinatal Arterial Stroke Treated With Stromal Cells Intranasally: 2-Year Safety and Neurodevelopment. Stroke. 2025 Sep;56(9):2410-2418. doi: 10.1161/STROKEAHA.125.050786. Epub 2025 Jul 14.

  PMID: 40654084 DERIVED

• Baak LM, Wagenaar N, van der Aa NE, Groenendaal F, Dudink J, Tataranno ML, Mahamuud U, Verhage CH, Eijsermans RMJC, Smit LS, Jellema RK, de Haan TR, Ter Horst HJ, de Boode WP, Steggerda SJ, Prins HJ, de Haar CG, de Vries LS, van Bel F, Heijnen CJ, Nijboer CH, Benders MJNL. Feasibility and safety of intranasally administered mesenchymal stromal cells after perinatal arterial ischaemic stroke in the Netherlands (PASSIoN): a first-in-human, open-label intervention study. Lancet Neurol. 2022 Jun;21(6):528-536. doi: 10.1016/S1474-4422(22)00117-X.

  PMID: 35568047 DERIVED

Results Point of Contact

• Title: Prof. M.J.N.L. Benders, MD, PhD, neonatologist
• Organization: UMC Utrecht, The Netherlands

m.benders@umcutrecht.nl

+31 88 755 5555

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Model Details: 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.

Study Record Dates

• First Submitted: November 8, 2017
• First Posted: November 29, 2017
• Study Start: February 11, 2020
• Primary Completion: July 27, 2021
• Study Completion: July 27, 2021
• Last Updated: May 13, 2024
• Results First Posted: May 13, 2024

Record last verified: 2023-12

Locations

NL (1)