Autologous BMMNCs Combined With Educational Intervention Versus Educational Intervention for ASD
Study Details
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 includes: Male/Female patients diagnosed with Autism disorder based on DSM-V scale, patient is between from 3 to 7 years old, 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 educational level of high school or above, patient's family has given consent to participate in the study. Exclusion criteria for treatment group includes: patient above 7 years of age and smaller than 3 year old, austistic 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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 for 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 were 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 level, 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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Autologous BMMNCs infusion combined with educational intervention Bone marrows are harvested from the patients' iliac depended on the patients' 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 muber verterbrea 4th and 5th. Two transplantations will be conducted with an interval of 6 months. The educational intervention will be developed based on 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), Clinical Global Impression (CGI). In addition, Health - related quality of life (HRQoL) in patients will be evaluated at baseline, 2 months, 6 months and 12 months with those in control group (educational intervention only) using 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 6 months after first administration. For each transplantation, bone marrow will be harvested through anterior iliac crest puncture under general anesthesia in the operating theatre. The volume collected depends on the patients' 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 Early Start Denver Model
|
| Active Comparator: Educational intervention alone (the controlled group) The educational intervention will be developed based on 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), Clinical Global Impression (CGI). In addition, Health - related quality of life (HRQoL) in patients will be evaluated at baseline, 2 months, 6 months and 12 months with those in control group (educational intervention only) using 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 6 months after first administration. For each transplantation, bone marrow will be harvested through anterior iliac crest puncture under general anesthesia in the operating theatre. The volume collected depends on the patients' 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 Early Start Denver Model
|
Outcome Measures
Primary Outcome Measures
- Change of severity of ASD after intervention through the Diagnostic and Statistical Manual of Mental Disorders [2 months, 6 months, 12 months after the first BMMNCs infusion]
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"), finally to (3) ("requiring very substantial support").
- Change of severity of ASD after intervention through the Childhood Autism Rating Scale [2 months, 6 months, 12 months after the first BMMNCs infusion]
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 [2 months, 6 months, 12 months after the first BMMNCs infusion]
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 85 or above (ie, 1 SD below the mean). This metric for "not impaired" is used in other optimal outcome studies and in the learning disability literature. We define growth as 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 [2 months, 6 months, 12 months after the first BMMNCs infusion]
The Clinical Global Impression Improvement (CGI) is a rating scale that measures symptom severity and treatment response. The severity is categorized into 7 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 7 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
- 1. Changes in health-related quality of life using Pediatric Quality of Life Inventory (PedsQL) [2 months, 6 months, 12 months after the first BMMNCs infusion]
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
Eligibility Criteria
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 serve level of autism (CARS score >=34 to 50)
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Patient's parent or caregiver must have educational level of high school or above
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Patient's family has given consent to participate in the study
Exclusion Criteria:
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Patient is above 7 years of age
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Autistic patient having epilepsy
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Patient with coagulation disorders
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Hydrocephalus with ventricular drain
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Allergy to anesthetic agnets
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Sever health conditions such as cancer, failure of heart, lung, liver, or kidney
-
Active infections
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Vinmec Research Institute of Stem Cell and Gene Technology | Hanoi | Vietnam | 10000 |
Sponsors and Collaborators
- Vinmec Research Institute of Stem Cell and Gene Technology
Investigators
- Principal Investigator: Liemg Nguyen, PhD, Vinmec Research Institute of Stem Cell and Gene Technology
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ISC.19.50