A Phase 1/2 interventional study of Wharton's jelly-derived mesenchymal stem cells and 0.9 % Normal Saline in Hypoxic-Ischemic Encephalopathy, Neonatal and Brain Injuries, Hypoxic-Ischemic, sponsored by Mahidol University. Not yet recruiting at 1 site in Thailand. Open to participants aged 4 Days to 9 Days. Per ClinicalTrials.gov, last updated 2026-09-02.
Sponsored by Mahidol University · Phase 1/2, Interventional, and Treatment
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.
Perinatal hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal death and long-term disability worldwide. Therapeutic hypothermia (TH) is the established standard of care for term and near-term infants with moderate to severe HIE. Large randomized trials and systematic reviews have demonstrated that TH significantly reduces the combined outcome of death or major neurodevelopmental disability at 18 months of age (relative risk 0.75; 95% confidence interval 0.68-0.83). However, despite this benefit, many infants continue to have poor outcomes. Importantly, a recent meta-analysis indicated that in upper-middle-income countries, the effect of TH was smaller and did not reach statistical significance (RR 0.67; 95% confidence interval 0.41-1.09), underscoring the need for effective adjunctive treatments.
Mesenchymal stem cells (MSCs) derived from Wharton's jelly of the human umbilical cord have emerged as a promising adjunctive therapy. Preclinical studies demonstrate that MSCs exert neuroprotective and regenerative effects via anti-inflammatory, anti-apoptotic, and trophic mechanisms. Early-phase clinical studies of cord blood or MSC products in neonatal HIE have shown feasibility and acceptable safety, with signals suggesting improved neurological recovery. Nevertheless, controlled trials specifically testing MSCs after completion of TH in neonates are lacking.
This study is a pilot, randomized, double-blind, placebo-controlled trial to evaluate the feasibility, safety, and potential efficacy of repeated intravenous infusions of Wharton's jelly-derived allogeneic MSCs in neonates with moderate to severe perinatal HIE who have completed TH. Forty infants (gestational age ≥34 weeks, postnatal age ≤10 days) will be randomized in a 1:1 ratio to receive either MSCs or placebo.
The intervention group will receive three intravenous doses of MSCs (2 × 10\^6 cells/kg per dose, suspended in normal saline) administered over approximately 30 minutes. The control group will receive equivalent volumes of placebo (normal saline). Infants, parents, and treating clinicians will remain blinded to allocation.
All cell products are prepared in a GMP-compliant cleanroom facility with rigorous quality control testing, including sterility, endotoxin, mycoplasma, viability, morphology, immunophenotype, and karyotype. Donor placental tissue undergoes standard infectious disease screening.
Participants will be continuously monitored during and after infusion in the neonatal intensive care unit. Prespecified safety endpoints include fever, sepsis, hemodynamic instability, seizure control, acute liver failure, acute kidney injury, thrombosis, and death. A Data Safety Monitoring Board (DSMB) will review interim safety data at 25%, 50%, and 75% enrollment, and at 50% of 1-year follow-up. Predefined stopping rules will apply if significant safety concerns are identified.
The primary outcome is the composite of death or neurodevelopmental disability at 1 year of age, defined by Bayley Scales of Infant and Toddler Development, Fourth Edition (BSID-IV) cognitive, language, or motor scores \<70. Secondary outcomes include hospital outcomes, brain MRI at 1 month (scored by Weeke criteria), HLA antibody formation at 9-12 months, and neurodevelopmental status at 2 years.
This pilot trial is designed to establish feasibility, evaluate safety, and generate preliminary efficacy estimates to inform future multicenter trials. All infants will receive standard TH and follow-up care, with the investigational therapy given only after cooling to test whether MSCs can further reduce death or disability in this high-risk population.
261 studies on the registry are indexed under Hypoxia-Ischemia, Brain; 95 are open to participants now.
This study's planned enrollment of 40 is below the median of 50 across 156 interventional studies indexed under Hypoxia-Ischemia, Brain.
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Exclusion Criteria:
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
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
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
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
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)
Time frame: At 12 months of age
Death or neurological disability
Any causes of death. Neurological disability is defined as Bayley Scales of Infant Development-IV \<70 (ranging from 40 to 160, with higher scores indicating better neurodevelopmental outcomes)
Time frame: At 24 months postnatal age
MR-detected brain injury
Brain injury detected by Weeke MRI score on brain MRI (total score range 0-57; higher scores indicate worse outcomes).
Time frame: At 1 month of age
Severe adverse events
One of these adverse events occurring after drug initiation: Hemodynamic instability (persistent HR \>180 beats per minute, BP \<5th %tile for gestational age and postnatal age, require new treatment (volume resuscitation/inotropic agents/vasopressor agents) Acute liver failure (new-onset of hyperbilirubinemia with INR ≥3 with no response to vitamin K administration) Thrombosis (any events such as renal vein thrombosis, stroke) Death before discharge
Time frame: From first study infusion until hospital discharge, up to 12 months
HLA antibody formation
Presence of anti-HLA antibodies assessed by panel-reactive antibody (PRA) testing.
Time frame: At 9-12 months of age
Length of birth hospitalization
Total days from birth to hospital discharge.
Time frame: Through hospital discharge, up to 12 months
Incidence of infection
Culture-proven infection requiring antimicrobial therapy.
Time frame: Through hospital discharge, up to 12 months
Serum concentrations of IL-6, IL-10, and TNF-α
Serum concentrations of IL-6, IL-10, and TNF-α will be measured from 1 mL blood samples collected at baseline (within 24 hours before administration of the first study dose) and at 24 and 72 hours after completion of the three-dose study treatment. Changes in biomarker concentrations over time will be compared between treatment groups.
Time frame: Baseline (within 24 hours before administration of the first study dose), and 24 and 72 hours after completion of the three-dose treatment regimen.
Plan to share: Yes — De-identified individual participant data underlying published results (e.g., baseline demographics, adverse events, primary and secondary outcomes including Bayley-IV scores and Weeke MRI scores).
Supporting information: Study protocol, Statistical analysis plan
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.
This study is not yet recruiting, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.
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