Autologous BMMNCs Combined With Educational Intervention for ASD

Autologous Bone Marrow Mononuclear Cell Transplantation Combined With Educational Intervention for Autism Spectrum Disorders (ASD): A Phase 2 Randomised Controlled Trial

The purpose of this study is to evaluate the safety and effectiveness of autologous bone marrow mononuclear cell infusion combined with educational intervention for children with autism spectrum disorder (ASD). Inclusion criteria: Male/Female patients diagnosed with Autism disorder based on DSM-V scale, the patient is between 3 to 7 years old, a patient has a medium level to server level of autism (CARS score>=30 to <50), VARS-2 >=50, patient's parent or caregiver must have the educational level of high school or above, patient's family has given consent to participate in the study. Exclusion criteria for treatment group: patient above seven years of age and smaller than 3-year old, autistic patients having epilepsy, hydrocephalus with ventricular drain, allergy to anesthetic agents, severe health conditions such as cancer, failure of heart, lung, liver, or kidney, active infections, children with birth defects of the spine.

Study Overview

• Status: Completed
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Combination product: Autologous BMMNCs transplantation and educational intervention; Combination product: Educational intervention

Detailed Description

A total of 54 patients with autism spectrum disorder (aged 3-7) will be recruited and divided into two groups: the control group (only intervention education) (n = 27) and the treatment group (bone marrow mononuclear cell transplantation combined intervention education (n =27). The bone marrow mononuclear cell will be applied to 27 patients in the treatment group infuse via the intrathecal administration. The primary outcome is measured by the number of AEs/SAEs during BMMNCs infusion. The secondary outcome was measured by clinical examinations performed at baseline and then at 02, 06, and 12 months after the first infusion. Multiple tools were used to diagnose and determine the severity of ASD, including DSM-5, CARS, the Vineland Adaptive Behavior Scales Second Edition (VABS-II), and the Clinical Global Impression (CGI). DSM-5, which was published in May 2013, provides new diagnostic criteria for ASD

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• Vietnam
  • Hanoi, Vietnam, 10000
    • Vinmec Research Institute of Stem Cell and Gene Technology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 7 years (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patient is between 3 to 7 years old
• Male/Female patient diagnosed with Autism disorder according to the diagnostic criteria for Autism Spectrum Disorder in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)
• Patient has a medium level to the most severe level of autism (CARS score >=34 to 50)
• Patient's parent or caregiver must have an educational level of high school or above
• Patient's family has given consent to participate in the study

Exclusion Criteria:

• Patient is above seven years of age
• Autistic patient having epilepsy
• Patient with coagulation disorders
• Hydrocephalus with ventricular drain
• Allergy to anesthetic agents
• Sever health conditions such as cancer, failure of heart, lung, liver, or kidney
• Active infections

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Autologous BMMNCs infusion combined with educational intervention; Bone marrows are harvested from the patient's iliac depending on the patient's body weight as follows: 8 ml/kg for patients under 10 kg; [80 ml + (body weight in kg - 10) × 7 ml] for patients above 10 kg. Mononuclear cells from collected bone marrow are infused intrathecally through a space between number vertebrae 4th and 5th. Two transplantations will be conducted at an interval of 6 months. The educational intervention will be developed based on the Early Start Denver Model for 6 months after the first infusion. Evaluation: The efficacy outcomes will be measured using the CARS, Vineland Adaptive Behavior Scales - second Edition (VABS), Autism Behavior Checklists (ABC), and Clinical Global Impression (CGI). In addition, Health-related quality of life (HRQoL) in patients will be evaluated at baseline, two months, six months, and 12 months with those in the control group (educational intervention only) using the Pediatric Quality of Life Inventory (PedsQL)	Combination product: Autologous BMMNCs transplantation and educational intervention; Biological/ Vaccine: Autologous bone marrow-derived mononuclear cell infusion (BM-MNCs) will be administrated at baseline, and the second infusion will be performed six months after the first administration. For each transplantation, the bone marrow will be harvested through an anterior iliac crest puncture under general anesthesia in the operating theatre. The volume collected depends on the patient's body weight based on our experience from a previous study as follows: 8 ml/kg for patients under 10 kg; [80 ml + (body weight in kg - 10) x 7 ml] for patients above 10 kg but no more than 250 ml in total. Educational intervention: 6 months based on the Early Start Denver Model
Active Comparator: Educational intervention (controlled group); The educational intervention will be developed based on the Early Start Denver Model for six months after enrollment. Evaluation: The efficacy outcomes will be measured using the CARS, Vineland Adaptive Behavior Scales - second Edition (VABS), Autism Behavior Checklists (ABC), and Clinical Global Impression (CGI). In addition, Health-related quality of life (HRQoL) in patients will be evaluated at baseline, two months, six months, and 12 months with those in the control group (educational intervention only) using the Pediatric Quality of Life Inventory (PedsQL)	Combination product: Educational intervention; Educational intervention: 6 months based on the Early Start Denver Model

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of severity of ASD after intervention through the Diagnostic and Statistical Manual of Mental Disorders	The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). DSM-5 describes three levels of increasing severity of ASD.DSM-5 describes three levels of increasing severity of ASD, from (1) ("requiring support") to (2) ("requiring substantial support"), and finally to (3) ("requiring very substantial support").	2 months, 6 months, 12 months after the first BMMNCs infusion
Change of severity of ASD after intervention through the Childhood Autism Rating Scale	The Childhood Autism Rating Scale (CARS) consists of 14 domains assessing behaviors associated with ASD, with a 15th domain rating general impressions of ASD. Each domain is scored on a scale ranging from one to four; higher scores are associated with a higher level of impairment. Total scores can range from a low of 15 to a high of 60; scores below 30 indicate that the individual is in the non-autistic range, scores between 30 and 36.5 indicate mild to moderate autism, and scores from 37 to 60 indicate severe autism.	2 months, 6 months, 12 months after the first BMMNCs infusion
Changes in social interaction; adaptive behaviour; daily living skills through Vineland Adaptive Behaviour Scale	The Vineland Adaptive Behaviour Scale second version (VABS-2) is a semi-structured interview measuring adaptive behavior with standard scores (M = 100, SD = 15). We define proficiency as a standard score of 85 or above (i.e., 1 SD below the mean). This metric for "not impaired" is used in other optimal outcome studies and the learning disability literature. We define growth as an improvement of at least 1 SD in standard scores (15 points) from T1 to T2. Improvement of 1 SD in clinical trials is considered a large effect size.	2 months, 6 months, 12 months after the first BMMNCs infusion
Changes in social interaction; adaptive behaviour; daily living skills through Clinical Global Impression Improvement	The Clinical Global Impression Improvement (CGI) is a rating scale that measures symptom severity and treatment response. The severity is categorized into seven levels: 1) not present (no ASD); 2) barely evident ASD symptoms; 3) mild ASD symptoms; 4) moderate ASD symptoms; 5) moderately severe ASD symptoms; 6) severe ASD symptoms or 7) very severe ASD symptoms. The response of each patient is also divided into seven levels: level 1) very much improved; level 2) much improved; level 3) minimally improved; level 4) no change; level 5) minimally worse; level 6) much worse; level 7) very much worse.	2 months, 6 months, 12 months after the first BMMNCs infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in health-related quality of life using Pediatric Quality of Life Inventory (PedsQL)	The Pediatric Quality of Life Inventory™ 4.0 Generic Core Scales - Parent Report (PedsQL) is a tool for assessing the HRQoL of children aged 2-18. PedsQL includes four domains (physical functioning, emotional functioning, social functioning, and school functioning) and is scored using three levels: no problems (1), some problems (2), or many problems (3). The PedsQL has 23 items, and scores on the standard portion range from 0 to 100, with 100 representing the best possible quality of life.	2 months, 6 months, 12 months after the first BMMNCs infusion

Collaborators and Investigators

• Sponsor: Vinmec Research Institute of Stem Cell and Gene Technology
• Investigators: Principal Investigator: Liemg Nguyen, PhD, Vinmec Research Institute of Stem Cell and Gene Technology

Publications and helpful links

General Publications

• Nguyen LT, Nguyen PM, Nguyen HP, Bui HT, Dao LTM, Van Pham M, Hoang CK, Nguyen PT, Nguyen TTP, Nguyen ATP, Hoang VT, Bui HTP, Vuong NK, Van Ngo D. Outcomes of autologous bone marrow mononuclear cell administration combined with educational intervention in the treatment of autism spectrum disorder: a randomized, open-label, controlled phase II clinical trial. Stem Cell Res Ther. 2025 May 30;16(1):268. doi: 10.1186/s13287-025-04404-4.
• Than UTT, Nguyen LT, Nguyen PH, Nguyen XH, Trinh DP, Hoang DH, Nguyen PAT, Dang VD. Inflammatory mediators drive neuroinflammation in autism spectrum disorder and cerebral palsy. Sci Rep. 2023 Dec 18;13(1):22587. doi: 10.1038/s41598-023-49902-8.

Study record dates

Study Major Dates

• Study Start (Actual): December 26, 2021
• Primary Completion (Actual): June 30, 2023
• Study Completion (Actual): December 30, 2023

Study Registration Dates

• First Submitted: February 12, 2022
• First Submitted That Met QC Criteria: March 23, 2022
• First Posted (Actual): April 1, 2022

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 20, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; Health Services; Health Care Facilities Workforce and Services; Child Health Services; Community Health Services; Preventive Health Services; Early Intervention, Educational
• Other Study ID Numbers: ISC.19.50

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No