Mesenchymal Stem Cells With Cooling Therapy for Infants With Hypoxic-Ischemic Encephalopathy

NCT07018739 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: Si 213/2025
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Hypoxic-ischemic encephalopathy (HIE) is a serious condition in newborns caused by lack of oxygen and blood flow around the time of birth. Standard treatment with cooling therapy (therapeutic hypothermia) lowers the risk of death or disability, but many infants still suffer long-term problems. This study will test whether adding stem cell therapy after cooling can further improve outcomes. The stem cells are taken from donated human placentas (Wharton's jelly-derived mesenchymal stem cells, MSCs). The cells are prepared under strict laboratory standards and checked for safety. Infants with moderate to severe HIE who have completed cooling will be randomly assigned to receive either three intravenous infusions of MSCs or placebo within the first 10 days of life. Each infusion is given over about 30 minutes while the infant is closely monitored. Researchers will follow participants for up to 2 years. The main outcome is whether MSC treatment can reduce the combined risk of death or serious developmental delay at 1 year of age. The study will also track brain MRI findings, safety events, and developmental progress at 2 years.

Conditions

Hypoxic-Ischemic Encephalopathy, Neonatal; Brain Injuries, Hypoxic-Ischemic

Keywords

Perinatal HIE; Mesenchymal stem cells; Wharton's jelly; therapeutic hypothermia

Outcome Measures

Primary Outcomes (1)

• Death or neurological disability

  Including any causes of deaths. Neurological disability is defined by Bayley Scales of Infant Development-IV \<70 (ranging from 40 to 160, with higher scores indicating better neurodevelopmental outcomes)

  At 12 months of age

Secondary Outcomes (6)

• Death or neurological disability

  At 24 months postnatal age

• MR-detected brain injury

  At 1 month of age

• Severe adverse events

  From first study infusion until hospital discharge, up to 12 months

• HLA antibody formation

  At 9-12 months of age

• Length of birth hospitalization

  Through hospital discharge, up to 12 months

Study Arms (2)

Wharton's jelly-derived mesenchymal stem cells

EXPERIMENTAL

A total of three IV infusions of MSCs will be administered, one dose per day for three consecutive days, starting within the first 10 days of life, following the completion of TH.

Biological: Wharton's jelly-derived mesenchymal stem cells

Placebo

PLACEBO COMPARATOR

A total of three IV infusions of 0.9%NSS will be administered, one dose per day for three consecutive days, starting within the first 10 days of life, following the completion of TH.

Drug: 0.9 % Normal Saline

Interventions

Wharton's jelly-derived mesenchymal stem cells BIOLOGICAL

MSCs (2x10\^6 cells/kg) in 10 mL 0.9%normal saline administered intravenously within 10 days, postnatally after TH completion, every 24 hours for 3 consecutive days

Also known as: mesenchymal stem cells

Wharton's jelly-derived mesenchymal stem cells

0.9 % Normal Saline DRUG

0.9% normal saline 10 mL administered intravenously within 10 days, postnatally after TH completion, every 24 hours for 3 consecutive days

Also known as: 0.9%NSS

Placebo

Eligibility Criteria

• Age: 4 Days - 9 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Term and late-preterm infants (gestational age ≥34 weeks)
• Diagnosed with moderate to severe HIE based on modified Sarnat staging
• Received TH per standard protocol
• Parental consent obtained

You may not qualify if:

• Major congenital anomalies or genetic syndromes
• Severe sepsis or active infection
• Severe coagulopathy or bleeding disorders
• Multi-organ failure

Sponsors & Collaborators

• Mahidol University: lead
• Siriraj Hospital: collaborator

Study Sites (1)

Siriraj Hospital, Mahidol University

Bangkok, 10700, Thailand

Location

Related Publications (16)

• Xu J, Feng Z, Wang X, Xiong Y, Wang L, Ye L, Zhang H. hUC-MSCs Exert a Neuroprotective Effect via Anti-apoptotic Mechanisms in a Neonatal HIE Rat Model. Cell Transplant. 2019 Dec;28(12):1552-1559. doi: 10.1177/0963689719874769. Epub 2019 Sep 12.

  PMID: 31512502 BACKGROUND

• Bruschettini M, Romantsik O, Moreira A, Ley D, Thebaud B. Stem cell-based interventions for the prevention of morbidity and mortality following hypoxic-ischaemic encephalopathy in newborn infants. Cochrane Database Syst Rev. 2020 Aug 19;8(8):CD013202. doi: 10.1002/14651858.CD013202.pub2.

  PMID: 32813884 RESULT

• Teo EJ, Jones LE, Wixey JA, Boyd RN, Colditz PB, Bjorkman ST. Combined hypothermia and mesenchymal stem cells in animal models of neonatal hypoxic-ischaemic encephalopathy: a systematic review. Pediatr Res. 2022 Jul;92(1):25-31. doi: 10.1038/s41390-021-01716-y. Epub 2021 Sep 4.

  PMID: 34482377 RESULT

• Ahn SY, Chang YS, Sung DK, Sung SI, Park WS. Hypothermia broadens the therapeutic time window of mesenchymal stem cell transplantation for severe neonatal hypoxic ischemic encephalopathy. Sci Rep. 2018 May 16;8(1):7665. doi: 10.1038/s41598-018-25902-x.

  PMID: 29769612 RESULT

• Terada K, Sasaki M, Nagahama H, Kataoka-Sasaki Y, Oka S, Ukai R, Yokoyama T, Iizuka Y, Sakai T, Fukumura S, Tsugawa T, Kocsis JD, Honmou O. Therapeutic efficacy of intravenous infusion of mesenchymal stem cells in rat perinatal brain injury. Pediatr Res. 2023 Dec;94(6):1921-1928. doi: 10.1038/s41390-023-02717-9. Epub 2023 Jul 8.

  PMID: 37422495 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• Ahn SY, Chang YS, Sung DK, Sung SI, Ahn JY, Park WS. Pivotal Role of Brain-Derived Neurotrophic Factor Secreted by Mesenchymal Stem Cells in Severe Intraventricular Hemorrhage in Newborn Rats. Cell Transplant. 2017 Jan 24;26(1):145-156. doi: 10.3727/096368916X692861. Epub 2016 Aug 16.

  PMID: 27535166 RESULT

• Lalu MM, McIntyre L, Pugliese C, Fergusson D, Winston BW, Marshall JC, Granton J, Stewart DJ; Canadian Critical Care Trials Group. Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials. PLoS One. 2012;7(10):e47559. doi: 10.1371/journal.pone.0047559. Epub 2012 Oct 25.

  PMID: 23133515 RESULT

• Mintoft A, Vallatos A, Robertson NJ. Mesenchymal Stromal Cell therapy for Hypoxic Ischemic Encephalopathy: Future directions for combination therapy with hypothermia and/or melatonin. Semin Perinatol. 2024 Aug;48(5):151929. doi: 10.1016/j.semperi.2024.151929. Epub 2024 Jun 13.

  PMID: 38902120 RESULT

• Dezawa M, Kanno H, Hoshino M, Cho H, Matsumoto N, Itokazu Y, Tajima N, Yamada H, Sawada H, Ishikawa H, Mimura T, Kitada M, Suzuki Y, Ide C. Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation. J Clin Invest. 2004 Jun;113(12):1701-10. doi: 10.1172/JCI20935.

  PMID: 15199405 RESULT

• Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol. 2008 Sep;8(9):726-36. doi: 10.1038/nri2395.

  PMID: 19172693 RESULT

• Braccioli L, Heijnen CJ, Coffer PJ, Nijboer CH. Delayed administration of neural stem cells after hypoxia-ischemia reduces sensorimotor deficits, cerebral lesion size, and neuroinflammation in neonatal mice. Pediatr Res. 2017 Jan;81(1-1):127-135. doi: 10.1038/pr.2016.172. Epub 2016 Sep 15.

  PMID: 27632779 RESULT

• Kaminski N, Koster C, Mouloud Y, Borger V, Felderhoff-Muser U, Bendix I, Giebel B, Herz J. Mesenchymal Stromal Cell-Derived Extracellular Vesicles Reduce Neuroinflammation, Promote Neural Cell Proliferation and Improve Oligodendrocyte Maturation in Neonatal Hypoxic-Ischemic Brain Injury. Front Cell Neurosci. 2020 Dec 10;14:601176. doi: 10.3389/fncel.2020.601176. eCollection 2020.

  PMID: 33362471 RESULT

• Nabetani M, Shintaku H, Hamazaki T. Future perspectives of cell therapy for neonatal hypoxic-ischemic encephalopathy. Pediatr Res. 2018 Jan;83(1-2):356-363. doi: 10.1038/pr.2017.260. Epub 2017 Nov 8.

  PMID: 29016557 RESULT

MeSH Terms

Conditions

Hypoxia-Ischemia, Brain; Brain Injuries

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypoxia, Brain; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Ratchada Kitsommart, MD

  Mahidol University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ratchada Kitsommart, MD

CONTACT

66961715544; ratchada.kit@mahidol.ac.th

Buranee Yangthara, MD, PhD

CONTACT

66843270809; buraneeyangthara@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Investigational product (MSCs or placebo) prepared by laboratory staff not involved in care or assessments. Syringes are identical in appearance and labeled only with subject codes. Clinical staff, investigators, and assessors remain blinded. Emergency unblinding allowed if medically necessary.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2025
• First Posted: June 12, 2025
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 1, 2032
• Study Completion (Estimated): December 1, 2033
• Last Updated: November 19, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 6 months after publication of the primary results, available for 5 years
• Access Criteria: Data will be available upon reasonable request to the Principal Investigator at Siriraj Hospital, subject to institutional review and data-sharing agreements.

Locations

TH (1)