Mesenchymal Stem Cells With Therapeutic Hypothermia for Infants With Perinatal Hypoxic-Ischemic Encephalopathy

Phase 1

Not yet recruiting

• Conditions: Perinatal Anoxic-ischemic Brain Injury; Mesenchymal Stem Cell
• Interventions: Drug: 0.9 % Normal Saline; Drug: Wharton's jelly-derived mesenchymal stem cells

• Registration Number: NCT07018739
• Lead Sponsor: Mahidol University

Brief Summary

Perinatal hypoxic-ischemic encephalopathy (HIE) remains a significant cause of neonatal morbidity and mortality. While therapeutic hypothermia (TH) has been established as the standard treatment, many infants continue to experience adverse neurodevelopmental outcomes. Mesenchymal stem cells (MSCs), known for their neuroprotective, anti-inflammatory, and regenerative properties, offer a promising adjunctive therapy.

The goal of this study is to evaluate the safety and feasibility of administering allogeneic Wharton's jelly-derived MSCs administered intravenously in neonates with moderate to severe HIE after receiving TH. The study population includes infants ≥34 weeks gestation diagnosed with moderate to severe HIE who have completed TH and are clinically stable.

The main questions it aims to answer are:

Does intravenous MSC administration after therapeutic hypothermia reduce the risk of death or neurological disability at 1 year of age compared to placebo? Does this intervention improve neurodevelopmental outcomes at 2 years of age? Researchers will compare infants randomized to receive MSCs with those receiving placebo to assess clinical safety, mortality, and neurodevelopmental outcomes.

Participants will:

Be randomly assigned to receive either a daily intravenous dose of MSCs or placebo for 3 consecutive days, with the first dose administered within the first 10 days of life.

Be monitored for immediate adverse events and vital signs during and after each administration.

Undergo serial follow-up assessments including neuroimaging at 1 month and neurodevelopmental evaluations at defined intervals up to 2 years of age.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-06-04
• Study First Submitted QC: 2025-06-04
• Last Update Submitted: 2025-06-04
• Study First Posted: 2025-06-12
• Last Update Posted: 2025-06-12
• Study Start: 2026-06
• Primary Completion: 2032-12
• Study Completion: 2034-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• 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

Exclusion Criteria

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	0.9 % Normal Saline	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.
MSCs	Wharton's jelly-derived mesenchymal stem cells	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.

Primary Outcome Measures

Name	Time	Method
Death or neurological disability	From enrollment to 12 months postnatal age	Including any causes of deaths. Neurological disability is defined by Bayley Scales of Infant Development-IV \<70

Secondary Outcome Measures

Name	Time	Method
Death or neurological disability	From enrollment to 24 months postnatal age	Any causes of death. Neurological disability is defined as Bayley Scales of Infant Development-IV \<70
MR-detected brain injury	at 1 months if age	Brain injury is detected by Weeke score
Severe adverse events	from drug administration until hospital discharge or postnatal age of 3 months	One of these adverse events occurring after drug initiation: Hemodynamic instability (persistent HR \>180 bpm, 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

Trial Locations

Locations (1)

Division of Neonatology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University; 🇹🇭 Bangkok, Thailand