Autologous Bone Marrow Mononuclear Cell Transplantation Combined With Rehabilitation in Children With Sequelae of Hypoxic-Ischemic Encephalopathy or Intracranial Hemorrhage

National Children's Hospital, Vietnam60 enrolled

Overview

This study evaluates the safety and preliminary efficacy of autologous bone marrow mononuclear cell transplantation combined with rehabilitation in children with neurological sequelae caused by hypoxic-ischemic brain injury or intracranial hemorrhage. Participants in the intervention group will receive autologous bone marrow aspiration, mononuclear cell transplantation via intrathecal route, and rehabilitation, while the control group will receive rehabilitation alone. Outcomes will be compared between groups over follow-up time points.

Neurological sequelae following hypoxic-ischemic brain injury and intracranial hemorrhage in children remain a major clinical challenge with limited effective treatment options. Rehabilitation is the current standard of care but often results in incomplete recovery. Autologous bone marrow mononuclear cell transplantation has emerged as a promising therapeutic approach due to its potential neuroregenerative and neuroprotective effects. This phase II study aims to evaluate the safety and preliminary efficacy of combining autologous bone marrow mononuclear cell transplantation with rehabilitation compared to rehabilitation alone. The study will also contribute to the development of a standardized technical protocol for this intervention.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Cerebral Palsy Hypoxic-Ischemic Encephalopathy Intracranial Hemorrhage

Interventions

Autologous Bone Marrow Mononuclear Cell TransplantationPROCEDURE

Autologous bone marrow mononuclear cells (BMMNCs) are collected from the patient's iliac crest under sterile conditions. Bone marrow aspiration is performed under appropriate anesthesia, followed by processing to isolate mononuclear cells using density gradient centrifugation. The prepared BMMNCs are administered via intrathecal injection under aseptic conditions. The dosage of cells is determined based on body weight and viability criteria. Patients are monitored for immediate and delayed adverse events following transplantation. In addition to cell transplantation, participants receive standardized rehabilitation therapy, including physical therapy, occupational therapy, and neurodevelopmental interventions, according to institutional protocols. This combined intervention aims to enhance neurological recovery through both regenerative cellular therapy and functional rehabilitation.

Eligibility

Sex: ALLMin age: 6 MonthsMax age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Children diagnosed with cerebral palsy * Age from 12 months to 72 months * Cerebral palsy caused by hypoxic-ischemic brain injury or intracranial hemorrhage * Gross Motor Function Classification System (GMFCS) level III to V * Completed required laboratory tests according to the study protocol * Written informed consent obtained from the child's parent or legal guardian Exclusion Criteria: * Children with acute infection at the time of screening or enrollment * Children with severe coagulopathy or contraindications to bone marrow aspiration * Children with severe systemic diseases (e.g., severe cardiac, hepatic, or renal failure) * Children with contraindications to anesthesia or intrathecal transplantation procedures * Children with a history of malignancy * Children who are unable to participate in or complete the rehabilitation program * Parents or legal guardians who do not provide informed consent

Outcomes

Primary Outcomes

Change in Gross Motor Function Measure (GMFM-88) total score from baseline to 12 months

Gross motor function will be assessed using the Gross Motor Function Measure (GMFM-88), a validated and standardized clinical scale for evaluating motor function in children with neurological impairment. The primary outcome is the change in GMFM-88 total score from baseline to 12 months. The change in score will be calculated and compared between the intervention group (autologous bone marrow mononuclear cell transplantation plus rehabilitation) and the control group (rehabilitation alone).

Time frame: Baseline and 12 months

Secondary Outcomes

Change in GMFM score at 3, 6, 9 months

Gross motor function will be assessed using the Gross Motor Function Measure (GMFM-88), a standardized clinical tool for children with cerebral palsy and related neurological impairment. The change in GMFM-88 total score from baseline to 3, 6,9 months will be calculated and compared between the intervention and control groups.

Time frame: Baseline and 3, 6, 9 months

Change in Gross Motor Function Classification System (GMFCS) level from baseline to 12 months

Gross motor function classification will be assessed using the Gross Motor Function Classification System (GMFCS), which categorizes motor function based on self-initiated movement abilities, particularly sitting and mobility. Changes in GMFCS level from baseline to 12 months will be evaluated and compared between the intervention and control groups.

Time frame: Baseline and 12 months

Change in Manual Ability Classification System (MACS or Mini-MACS) level from baseline to 12 months

Manual ability will be assessed using the Manual Ability Classification System (MACS) or Mini-MACS depending on the child's age. Changes in manual ability level from baseline to 12 months will be evaluated and compared between the intervention and control groups.

Time frame: Baseline and 12 months

Incidence of transplantation-related adverse events

Adverse events related to bone marrow aspiration, anesthesia, intrathecal transplantation, and follow-up will be recorded. These include local pain at the aspiration site, low back pain after transplantation, fever, irritability, vomiting, rash, and other procedure-related complications. The incidence and severity of adverse events will be monitored and summarized throughout the study.

Time frame: From intervention through 12 months follow-up

Autologous Bone Marrow Mononuclear Cell Transplantation Combined With Rehabilitation in Children With Sequelae of Hypoxic-Ischemic Encephalopathy or Intracranial Hemorrhage

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts