hCT-MSC in Children With Autism Spectrum Disorder (IMPACT)

A Phase II Study of hCT-MSC, an Umbilical Cord-Derived Mesenchymal Stromal Cell Product, in Children With Autism Spectrum Disorder

The purpose of this Phase II study is to determine the efficacy of human umbilical cord tissue-derived mesenchymal stromal cells (hCT-MSC) for improving social communication abilities in children with autism spectrum disorder (ASD).

Study Overview

• Status: Completed
• Conditions: Autism Spectrum Disorder; Autism
• Intervention / Treatment: Biological: Cord Tissue Mesenchymal Stromal Cells; Other: Placebo Infusion

Detailed Description

The purpose of this double blinded Phase II study is to determine the efficacy of human umbilical cord tissue-derived mesenchymal stromal cells (hCT-MSC), administered in two different dosing strategies, in children with autism spectrum disorder (ASD).

This study will be enrolling children with ASD, aging 4-11 years of age. Qualifying subjects will undergo neuropsychological evaluation, EEG testing, eye tracking, CVA assessments, and infusion of study product. Subjects will be randomized to one of two study arms; 1) a single infusion of 6.0x106 cells/Kg at baseline, followed by a blinded placebo infusion at six months or, 2) Placebo infusion at baseline, followed by an intravenous dose of 6x106 cells/Kg at six months. The second infusion was included primarily as an incentive to ensure that all participants ultimately receive an infusion of MSC, to reduce the risk of unblinding, and to encourage study completion. Efficacy outcome measures were only evaluated 6 months before the second infusion. Safety outcomes were assessed during the entire 12 months of the study.

The primary endpoint of this study is the change in social communication skill from baseline to six months. The potential risks associated with infusion of MSCs include a reaction to the product (rash, shortness of breath, wheezing, difficulty breathing, hypotension, swelling around the mouth, throat or eyes, tachycardia, diaphoresis), transmission of infection, and HLA sensitization.

• Study Type: Interventional
• Enrollment (Actual): 137
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 11 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Age ≥ 4 years to < 12 years (11 years, 364 days) at the time of consent
2. Confirmed clinical DSM-5 diagnosis of Autism Spectrum Disorder using the DSM-5 Checklist as informed by the Brief Observation of Symptoms of Autism (BOSA) and the Autism Diagnostic Interview-Revised (ADI-R)
3. Fragile X testing performed and negative; CMA and/or whole exome sequencing performed and results not linked to autism diagnosis
4. Stable on current psychiatric medication regimen (dose and dosing schedule) for at least 2 months prior to infusion of study product
5. Normal absolute lymphocyte count (≥1200/uL for African American participants and ≥1500/uL for all other participants)
6. GAI ≥ 65 via cognitive testing by study personnel
7. Participant and parent/guardian are English speaking
8. Able to travel to Duke University two times (baseline, six months), and parent/guardian is able to participate in interim surveys and interviews
9. Parental/guardian consent from at least one parent/guardian

Exclusion Criteria

1. General:

   1. Review of medical records and/or screening assessments indicates ASD diagnosis and/or GAI > 65 not confident
   2. Known diagnosis of any of the following coexisting psychiatric conditions: depression, bipolar disorder, schizophrenia, obsessive compulsive disorder associated with bipolar disorder, Tourette syndrome
   3. Screening data suggests that participant would not be able to comply with the requirements of the study procedures as assessed by the study team
   4. Family is unwilling or unable to commit to participation in all study-related assessments, including protocol follow up
   5. Sibling is enrolled in this (Duke IMPACT) study

2. Genetic:

   1. Records indicate that child has a known genetic syndrome such as (but not limited to) Fragile X syndrome, neurofibromatosis, Rett syndrome, tuberous sclerosis, PTEN mutation, cystic fibrosis, muscular dystrophy or a genetic defect definitively known to be associated with ASD
   2. Known pathogenic mutation or copy number variation (CNV) associated with ASD (e.g., 16p11.2, 15q13.2, 2q13.3)

3. Infectious:

   1. Known active CNS infection
   2. Evidence of uncontrolled infection based on records or clinical assessment
   3. Known HIV positivity
   4. Exposure to COVID-19 in the preceding 14 days or positive COVID-19 test in the previous 28 days. Subjects with a past history of infection with COVID-19 must be symptom-free for 14 days prior to the initial visit.

4. Medical:

   1. Known metabolic disorder
   2. Known mitochondrial dysfunction
   3. History of unstable epilepsy or uncontrolled seizure disorder, infantile spasms, Lennox Gastaut syndrome, Dravet syndrome, or other similar chronic seizure disorder
   4. Active malignancy or prior malignancy that was treated with chemotherapy
   5. History of a primary immunodeficiency disorder
   6. History of autoimmune cytopenias (i.e., ITP, AIHA)
   7. Coexisting medical condition that would place the child at increased risk for complications of study procedures
   8. Concurrent genetic or acquired disease or comorbidity(ies) that could require a future stem cell transplant
   9. Significant sensory (e.g., blindness, deafness, uncorrected hearing impairment) or motor (e.g., cerebral palsy) impairment
   10. Impaired renal or liver function as determined by serum creatinine >1.5mg/dL or total bilirubin >1.3mg/dL, except in patients with known Gilbert's disease
   11. Significant hematologic abnormalities defined as: Hemoglobin <10.0 g/dL, Platelets <150 x 10e9/uL, WBC <3,000 cells/mL, ALC <1200/uL for African Americans or <1500/uL for all other participants.
   12. Evidence of clinically relevant physical dysmorphology indicative of a genetic syndrome as assessed by the PIs or other investigators, including a medical geneticist and psychiatrists trained in identifying dysmorphic features associated with neurodevelopmental conditions.

5. Current/Prior Therapy:

   a. Availability of a banked, qualified autologous cord blood unit or parents deferred use of qualified, autologous cord blood unit b. History of prior cell therapy c. Current or prior use of IVIG or other anti-inflammatory medications with the exception of NSAIDs d. Current or prior immunosuppressive therapy i. No systemic steroid therapy that has lasted >2 weeks, and no systemic steroids within 3 months prior to enrollment. Topical and inhaled steroids are permitted.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MSC; One dose of 6x10e6 cells/kg administered intravenously.	Biological: Cord Tissue Mesenchymal Stromal Cells; Human Umbilical Cord Tissue Derived Mesenchymal Stromal Cells (hCT-MSC), isolated and expanded from umbilical cord tissue from allogeneic unrelated donors. One dose of 6x10e6 cells/kg administered intravenously.
Placebo Comparator: Placebo Infusion; Placebo infusion	Other: Placebo Infusion; Placebo comparative infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change on the Average Socialization and Communication Subscale Standard Scores on the Vineland Behavior Scales (VABS-3)	The primary outcome measure is the mean of the Socialization and Communication Subscale Standard Scores on the Vineland Adaptive Behavior Scales (VABS-3) from the Comprehensive Interview form. The primary endpoint is the change in this outcome measure from baseline to six months before the second infusion. A positive change in the scores indicates an improvement in socialization and communication. A standard score of 100 is the mean with a standard deviation of 15 points. A score of 100 should be understood as being similar to the typical population of the same age. Scores greater than or equal to 86 are considered adequate or above adequate. Domain scores less than or equal to 85 are considered moderately low to low and indicate the patient has a significant skill deficit when compared with similarly aged peers.	Baseline, 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in VABS-3 (Vineland Adaptive Behavior Scales) Socialization Standard Score	The change in the Socialization Subscale Standard Scores on the Vineland Adaptive Behavior Scales (VABS-3) from baseline to six months. Higher Socialization Standard scores indicate greater socialization. A positive change in the scores indicates an improvement in socialization. A standard score of 100 is the mean with a standard deviation of 15 points. A score of 100 should be understood as being similar to the typical population of the same age. Scores greater than or equal to 86 are considered adequate or above adequate. Domain scores less than or equal to 85 are considered moderately low to low and indicate the patient has a significant skill deficit when compared with similarly aged peers.	Baseline, 6 months
Change in VABS-3 Communication Standard Score	The change in the Communication Standard Scores on the Vineland Adaptive Behavior Scales (VABS-3) from the Comprehensive Interview form from baseline to six months before the second infusion. Higher scores indicate greater communication. A positive change in the scores indicates an improvement in communication. A standard score of 100 is the mean with a standard deviation of 15 points. A score of 100 should be understood as being similar to the typical population of the same age. Scores greater than or equal to 86 are considered adequate or above adequate. Domain scores less than or equal to 85 are considered moderately low to low and indicate the patient has a significant skill deficit when compared with similarly aged peers.	Baseline, 6 months
CGI-S (Clinical Global Impression - Severity of Illness) Overall Score	The CGI-S Overall Score is a 7-point scale that requires the clinician to rate the severity of the participant's overall functioning and symptoms of autism at the time of assessment, relative to the clinician's experience with participants who have the same diagnosis. The clinician rates the severity of autism symptoms - 1, normal, no symptoms; 2, borderline level of symptoms; 3, mild symptoms; 4, moderate symptoms; 5, marked symptoms; 6, severe symptoms; or 7, extremely severe symptoms. The higher ratings indicate greater severity of overall functioning impairment.	6 months
CGI-I (Clinical Global Impression - Improvement) Overall Score	The CGI-I Overall Score is a 7-point scale that requires the clinician to assess how much the participant's autism overall functioning and symptoms have improved or worsened relative to a baseline assessment. The symptoms are rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. The lower scores indicate greater improvement.	6 months
Change in the Pediatric Quality of Life (PedsQL) Total Scale Score	The PedsQL 4.0 Generic Core Scales is a 5-minute parent questionnaire that measures the child's functioning in the dimensions of physical, emotional, social, and school. The items use a Likert rating scale from 0 (Never) to 4 (Almost Always). This 0-4 scale is then transformed to 0=100, 1=75, 2=50, 3=25, and 4=0 for a reverse score. The Total Scale Score is then computed as the sum of all the items over the number of items answered on all the Scales for a total score range of 0 to 100. Higher scores indicate a better quality of life.	Baseline, 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Experiencing an Infusion Reaction	To assess safety, participants were considered according to the treatment received at each time point, not what they were randomized. Patients received the infusion to which they were randomized at baseline and the alternate treatment at 6 months. Therefore, adverse events are reported by randomized treatment arm broken into periods: 0-6 months (post-baseline infusion, pre-six month infusion) and 6-12 months (post-six month infusion).	up to 12 months
Number of Participants Experiencing Product-related Infections	To assess safety, participants were considered according to the treatment received at each time point, not to what they were randomized. Patients received the infusion to which they are randomized at baseline, and the alternate treatment at 6 months. AEs are reported by randomized treatment arm broken into periods: 0-6 months (post-baseline infusion, pre-six month infusion) and 6-12 months (post-six month infusion). 6-12 month evaluation time points are further broken into whether or not the participant received a second infusion, since three MSC patients and one Placebo patient did not receive the 6-month incentive infusion but were still evaluated.	up to 12 months
Evidence of Formation of Anti-HLA Antibodies	Assess for anti-HLA antibodies	Baseline, 6 months, 12 months
Number of Participants Experiencing Graft Versus Host Disease (GVHD)	To assess safety, participants were considered according to the treatment received at each time point, not to what they were randomized. Patients received the infusion to which they are randomized at baseline, and the alternate treatment at 6 months. AEs are reported by randomized treatment arm broken into periods: 0-6 months (post-baseline infusion, pre-six month infusion) and 6-12 months (post-six month infusion). 6-12 month evaluation time points are further broken into whether or not the participant received a second infusion, since three MSC patients and one Placebo patient did not receive the 6-month incentive infusion but were still evaluated.	up to 12 months
Number of Participants Experiencing Unexpected Adverse Events Related to the Study Product	To assess safety, participants were considered according to the treatment received at each time point, not to what they were randomized. Patients received the infusion to which they are randomized at baseline, and the alternate treatment at 6 months. AEs are reported by randomized treatment arm broken into periods: 0-6 months (post-baseline infusion, pre-six month infusion) and 6-12 months (post-six month infusion). 6-12 month evaluation time points are further broken into whether or not the participant received a second infusion, since three MSC patients and one Placebo patient did not receive the 6-month incentive infusion but were still evaluated.	up to 12 months
Change on the Adaptive Behavior Composite Subscale Standard Score on the Vineland Behavior Scales (VABS-3)	The change in the Vineland Adaptive Behavior Scales (VABS-3) Adaptive Behavior Composite Subscale from baseline to 6 months before the second infusion. Higher Adaptive Behavior Composite Standard scores indicate greater adaptive behavior. A positive change in the scores indicates an improvement in adaptive behavior. A standard score of 100 is the mean with a standard deviation of 15 points. A score of 100 should be understood as being similar to the typical population of the same age. Scores greater than or equal to 86 are considered adequate or above adequate. Domain scores less than or equal to 85 are considered moderately low to low and indicate the patient has a significant skill deficit when compared with similarly aged peers.	Baseline, 6 months
Change in VABS-3 (Vineland Adaptive Behavior Scales) Daily Living Skills Standard Score	The change in the Daily Living Skills Subscale Standard Scores on the Vineland Adaptive Behavior Scales (VABS-3) from baseline to six months before the second infusion. Higher Daily Living Skills Standard scores indicate greater daily living skills. A positive change in the scores indicates an improvement in daily living skills. A standard score of 100 is the mean with a standard deviation of 15 points. A score of 100 should be understood as being similar to the typical population of the same age. Scores greater than or equal to 86 are considered adequate or above adequate. Domain scores less than or equal to 85 are considered moderately low to low and indicate the patient has a significant skill deficit when compared with similarly aged peers.	Baseline, 6 months
Change in VABS-3 Motor Skills Standard Score	The change in the Motor Skills Standard Scores on the Vineland Adaptive Behavior Scales (VABS-3) from the Comprehensive Interview form from baseline to six months before the second infusion. Higher scores indicate greater motor skills. A positive change in the scores indicates an improvement in motor skills. A standard score of 100 is the mean with a standard deviation of 15 points. A score of 100 should be understood as being similar to the typical population of the same age. Scores greater than or equal to 86 are considered adequate or above adequate. Domain scores less than or equal to 85 are considered moderately low to low and indicate the patient has a significant skill deficit when compared with similarly aged peers.	Baseline, 6 months
Change in Aberrant Behavior Checklist-Community (ABC-C) Social Withdrawal	The change in the Aberrant Behavior Checklist-Community (ABC-C) Social Withdrawal scale from baseline to six months before the second infusion. Higher scores indicate greater problems with social withdrawal. A positive change in the scores indicates a worsening in social withdrawal. This scale has 16 items that are scored on a 4-point Likert scale: 0 = not a problem, 1 = slight problem, 2 = moderately serious problem, 3 = severe problem. The individual items are added together to calculate the Social Withdrawal scale score.	Baseline, 6 months
Change in Pervasive Developmental Disorder Behavior Inventory (PDDBI) Total Score	The change in the Pervasive Developmental Disorder Behavior Inventory (PDDBI) from baseline to 6 months before the second infusion. The PDDBI is a measure of problem behaviors and social, language, and learning or memory skills of children who have been diagnosed with autism spectrum disorder. Raw scores are converted to T-scores. The T-score has a mean of 50 with a standard deviation of 10 points with a range of 10-100. Higher scores indicate greater behavioral issues and a positive change in score indicates worsening.	Baseline, 6 months
Change in the Autism Impact Measure (AIM)	The change in the Autism Impact Measure (AIM) from baseline to 6 months before second infusion. AIM is a measure of core Autism Spectrum Disorder Symptoms. It is a parent-report questionnaire that includes 41 core-symptom items rated on two corresponding 5-point scales: frequency (ranging from "never" to "always") and impact (ranging from "not at all" to "severely") over the previous two weeks. Frequency and impact ratings are combined, yielding a total score range of 82 to 410. Higher scores indicate greater symptom severity; a positive change in score indicates worsening of symptoms.	Baseline, 6 months
Change in the Behavior Rating Inventory of Executive Function (BRIEF) Emotional Control Subscale	The change in the Behavior Rating Inventory of Executive Function (BRIEF) Emotional Control subscale from baseline to month 6 before the second infusion. BRIEF is a survey that assesses executive function and self-regulation with the following subscales: Inhibit, Shift, Emotional Control, Working Memory, and Planning and Organization. Higher scores indicate greater levels of dysfunction each respective domain. A positive change in score indicates worsening the respective domain. Raw scores for each domain are converted to t-scores (Mean = 50, SD = 10) and percentiles. T scores 60-64 are considered to be mildly elevated, 65-69 are considered to be potentially clinically elevated, and >= 70 are considered to be clinically elevated.	Baseline, 6 months
Change in the Behavior Rating Inventory of Executive Function (BRIEF) Working Memory Subscale	The change in the Behavior Rating Inventory of Executive Function (BRIEF) Working Memory subscale from baseline to month 6 before the second infusion. The BREIF is a survey that assesses executive function and self-regulation with the following subscales: Inhibit, Shift, Emotional Control, Working Memory, and Planning and Organization. Higher scores indicate greater levels of dysfunction each respective domain. A positive change in score indicates worsening the respective domain. Raw scores for each domain are converted to t-scores (Mean = 50, SD = 10) and percentiles. T scores 60-64 are considered to be mildly elevated, 65-69 are considered to be potentially clinically elevated, and >= 70 are considered to be clinically elevated.	Baseline, 6 months
Change in the Behavior Rating Inventory of Executive Function (BRIEF) Inhibit Subscale	The change in the Behavior Rating Inventory of Executive Function (BRIEF) Inhibit subscale from baseline to month 6 before the second infusion. The BRIEF is a survey that assesses executive function and self-regulation with the following subscales: Inhibit, Shift, Emotional Control, Working Memory, and Planning and Organization. Higher scores indicate greater levels of dysfunction each respective domain. A positive change in score indicates worsening the respective domain. Raw scores for each domain are converted to t-scores (Mean = 50, SD = 10) and percentiles. T scores 60-64 are considered to be mildly elevated, 65-69 are considered to be potentially clinically elevated, and >= 70 are considered to be clinically elevated.	Baseline, 6 months
Change in the Behavior Rating Inventory of Executive Function (BRIEF) Plan/Organization Subscale	The change in the Behavior Rating Inventory of Executive Function (BRIEF) Plan/Organization subscale from baseline to month 6 before the second infusion. The BRIEF is a survey that assesses executive function and self-regulation with the following subscales: Inhibit, Shift, Emotional Control, Working Memory, and Planning and Organization. Higher scores indicate greater levels of dysfunction each respective domain. A positive change in score indicates worsening the respective domain. Raw scores for each domain are converted to t-scores (Mean = 50, SD = 10) and percentiles. T scores 60-64 are considered to be mildly elevated, 65-69 are considered to be potentially clinically elevated, and >= 70 are considered to be clinically elevated.	Baseline, 6 months
Change in the Behavior Rating Inventory of Executive Function (BRIEF) Shift Subscale	The change in the Behavior Rating Inventory of Executive Function (BRIEF) Shift subscale from baseline to month 6 before the second infusion. The BRIEF is a survey that assesses executive function and self-regulation with the following subscales: Inhibit, Shift, Emotional Control, Working Memory, and Planning and Organization. Higher scores indicate greater levels of dysfunction each respective domain. A positive change in score indicates worsening the respective domain. Raw scores for each domain are converted to t-scores (Mean = 50, SD = 10) and percentiles. T scores 60-64 are considered to be mildly elevated, 65-69 are considered to be potentially clinically elevated, and >= 70 are considered to be clinically elevated.	Baseline, 6 months
Change in the Expressive Vocabulary Test (Third Edition, EVT-3)	The change in the Expressive Vocabulary Test (Third Edition, EVT-3) from baseline to 6 months before the second infusion. The EVT-3 is a measure of a participant's ability to match a spoken word with an image of an object, action, or concept. The number of words that are retrieved is converted to a Standard Score, where 100 is the mean with a standard deviation of 15 points. A score of 100 should be understood as being similar to the typical population of the same age. Scores greater than or equal to 86 are considered adequate or above adequate. Scores less than or equal to 85 are considered moderately low to low and indicate the patient has a significant skill deficit when compared with similarly aged peers. A positive change in EVT-3 score indicates improvement.	Baseline, 6 months

Collaborators and Investigators

• Sponsor: Joanne Kurtzberg, MD
• Collaborators: The Marcus Foundation; Cryo-Cell International
• Investigators: Principal Investigator: Lauren Franz, MBChB, Duke University; Principal Investigator: Beth Shaz, MD, Duke University

Publications and helpful links

General Publications

• Chatham CH, Taylor KI, Charman T, Liogier D'ardhuy X, Eule E, Fedele A, Hardan AY, Loth E, Murtagh L, Del Valle Rubido M, San Jose Caceres A, Sevigny J, Sikich L, Snyder L, Tillmann JE, Ventola PE, Walton-Bowen KL, Wang PP, Willgoss T, Bolognani F. Adaptive behavior in autism: Minimal clinically important differences on the Vineland-II. Autism Res. 2018 Feb;11(2):270-283. doi: 10.1002/aur.1874. Epub 2017 Sep 21.

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2020
• Primary Completion (Actual): May 2, 2023
• Study Completion (Actual): February 1, 2024

Study Registration Dates

• First Submitted: September 12, 2019
• First Submitted That Met QC Criteria: September 12, 2019
• First Posted (Actual): September 13, 2019

Study Record Updates

• Last Update Posted (Actual): June 24, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Autism; Autism Spectrum Disorder; Stem cell; Mesenchymal Stromal Cells
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; Autistic Disorder
• Other Study ID Numbers: Pro00113011; Pro00102894 (Other Identifier: Duke IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No