Autologous BMMNCs Combined With Educational Intervention for ASD

Back to results

Primary Purpose

Status

Recruiting

Phase

Phase 2

Locations

Vietnam

Study Type

Interventional

Intervention

Autologous BMMNCs transplantation and educational intervention

Educational intervention

About this trial

This is an interventional treatment trial for Autism Spectrum Disorder

Eligibility Criteria

3 Years - 7 Years (Child)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Vinmec Research Institute of Stem Cell and Gene TechnologyRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Autologous BMMNCs infusion combined with educational intervention

Educational intervention (controlled group)

Arm Description

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)

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)

Outcomes

Primary Outcome Measures

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").

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.

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.

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.

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT05307536

First Posted

February 12, 2022

Last Updated

August 23, 2022

Sponsor

Vinmec Research Institute of Stem Cell and Gene Technology

1. Study Identification

Unique Protocol Identification Number

NCT05307536

Brief Title

Autologous BMMNCs Combined With Educational Intervention for ASD

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2021

Overall Recruitment Status

Recruiting

Study Start Date

December 26, 2021 (Actual)

Primary Completion Date

June 30, 2023 (Anticipated)

Study Completion Date

June 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Vinmec Research Institute of Stem Cell and Gene Technology

4. Oversight

Studies a U.S. FDA-regulated Drug Product

No

Studies a U.S. FDA-regulated Device Product

No

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Autism Spectrum Disorder

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

A total of 54 patients with autism spectrum disorder (3-7 years old) will be recruited and divided into two groups: the controlled group (only intervention education) (n = 27) and the treatment group (Bone marrow mononuclear cell infusions combined educational intervention (n =27)

Masking

None (Open Label)

Allocation

Randomized

Enrollment

54 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Autologous BMMNCs infusion combined with educational intervention

Arm Type

Experimental

Arm Description

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)

Arm Title

Educational intervention (controlled group)

Arm Type

Active Comparator

Arm Description

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)

Intervention Type

Combination Product

Intervention Name(s)

Autologous BMMNCs transplantation and educational intervention

Intervention Description

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

Intervention Type

Combination Product

Intervention Name(s)

Educational intervention

Intervention Description

Educational intervention: 6 months based on the Early Start Denver Model

Primary Outcome Measure Information:

Title

Change of severity of ASD after intervention through the Diagnostic and Statistical Manual of Mental Disorders

Description

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").

Time Frame

2 months, 6 months, 12 months after the first BMMNCs infusion

Title

Change of severity of ASD after intervention through the Childhood Autism Rating Scale

Description

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.

Time Frame

2 months, 6 months, 12 months after the first BMMNCs infusion

Title

Changes in social interaction; adaptive behaviour; daily living skills through Vineland Adaptive Behaviour Scale

Description

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.

Time Frame

2 months, 6 months, 12 months after the first BMMNCs infusion

Title

Changes in social interaction; adaptive behaviour; daily living skills through Clinical Global Impression Improvement

Description

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.

Time Frame

2 months, 6 months, 12 months after the first BMMNCs infusion

Secondary Outcome Measure Information:

Title

Changes in health-related quality of life using Pediatric Quality of Life Inventory (PedsQL)

Description

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.

Time Frame

2 months, 6 months, 12 months after the first BMMNCs infusion

10. Eligibility

Sex

All

Minimum Age & Unit of Time

3 Years

Maximum Age & Unit of Time

7 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Liem Nguyen, PhD

Phone

0986565015

Email

v.liemnt@vinmec.com

First Name & Middle Initial & Last Name or Official Title & Degree

Phuong Nguyen, MsC

Phone

0914740683

Email

v.phuongnh9@vinmec.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Liemg Nguyen, PhD

Organizational Affiliation

Vinmec Research Institute of Stem Cell and Gene Technology

Official's Role

Principal Investigator

Facility Information:

Facility Name

Vinmec Research Institute of Stem Cell and Gene Technology

City

Hanoi

ZIP/Postal Code

10000

Country

Vietnam

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Phuong Nguyen, MPH

Phone

(+84)914740683

Email

hoangphuonghsph@gmail.com

First Name & Middle Initial & Last Name & Degree

Liem Nguyen, Prof

Autism Spectrum Disorder

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial