hCT-MSC Infusion in Adults With Autism Spectrum Disorder (AIMs)
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|ClinicalTrials.gov Identifier: NCT04484077|
Recruitment Status : Not yet recruiting
First Posted : July 23, 2020
Last Update Posted : November 13, 2020
|Condition or disease||Intervention/treatment||Phase|
|Autism Spectrum Disorder Autism||Biological: hCT-MSC||Phase 1|
This is a prospective, open label, phase one study to determine the safety and tolerability of a single intravenous dose of Human Umbilical Cord Tissue Derived Mesenchymal Stromal Cells (hCT-MSC) in adults with autism spectrum disorder (ASD). hCT-MSCs are manufactured from umbilical cord tissue donated by healthy mothers delivering full term babies via Cesarean Section. The cells are extracted from the cord tissue, expanded and cryopreserved (frozen). One dose of 2x10^6 cells/kg (maximum of 10 x 10^7) will be administered intravenously to each participant in this study.
It is hypothesized that immune dysregulation and/or abnormal neuronal connectivity that adversely affects normal brain development may cause core symptomatology observed in individuals with ASD. Mesenchymal stromal cells (MSC) have demonstrated a multitude of immunomodulatory effects which are thought to be carried out via paracrine and trophic signaling. While MSCs modulate the immune response, MSCs themselves have low immunogenicity (the body does not have a strong immune reaction against them) and they do not permanently engraft in the recipient.
Adults ages 18 to 35 years with ASD will be eligible to participate. All participants will have a screening visit that includes clinical evaluation to verify the diagnosis of ASD, cognitive abilities, ASD symptom level, and confirmation of eligibility.
One dose of 2x10^6 cells/kg (maximum of 10 x 10^7) will be administered intravenously to each participant at a baseline visit. Participants will be admitted to the infusion center on the day of their baseline visit and vital signs (heart rate, blood pressure, temperature, respiratory rate) will be measured. Participants may require some sedation prior to IV placement if they are unable to remain still or cooperate. A peripheral IV will be placed and prior to the infusion, premedications (Benadryl, Solumedrol, 0.5mg/kg each) will be administered. The hCT-MSCs product will be administered intravenously over 30-60 minutes. Pulse oximetry will be monitored continuously throughout the infusion and IV fluid maintenance will be given. Participants will be discharged after 1 hour, providing all vital signs are at their baseline and they are asymptomatic with no evidence of toxicity. Participants will be evaluated the day after the infusion to assess for any infusion-related adverse reactions or complications. A phone call or email to the participant or legally authorized representative to assess safety of the infusion will occur 7-10 days after the infusion. Remote follow up will occur 3 months and one year after infusion. Participants will return to Duke six months after infusion for repeated testing and safety follow-up. The Medical and Behavioral History Questionnaire assessing adverse events will be obtained at baseline, 3, 6 and 12-months.
The main endpoint is safety, for which acute infusion reactions, incidence of infections, and markers of alloimmunization will be assessed. Key secondary endpoints will include ASD-specific outcome measures to describe any changes in autism symptoms after product administration. Exploratory analyses will include measures obtained by EEG, eye-tracking, pupillary light reflex, computer vision analysis, and tactile stimulation.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A PHASE I STUDY OF hCT-MSC, AN UMBILICAL CORD-DERIVED MESENCHYMAL STROMAL CELL PRODUCT, IN ADULTS WITH AUTISM SPECTRUM DISORDER|
|Estimated Study Start Date :||January 2021|
|Estimated Primary Completion Date :||March 2023|
|Estimated Study Completion Date :||March 2023|
Experimental: hCT-MSC infusion
A single, intravenous infusion of hCT-MSCs. Targeted dose is 2x10^6 cells/kg with a maximum dose of 10 x 10^7 cells/kg.
2x10^6 hCT-MSC/kg suspended in plasmalyte-A, 5% HSA, and residual DMSO/dextran administered intravenously over 30-60 minutes via syringe pump
- Incidence of infusion reactions [ Time Frame: Baseline through 10 days post infusion ]cumulative incidence as measured by clinical examination and patient interview
- Incidence of product-related infections [ Time Frame: Baseline through 12 months ]cumulative incidence as measured by patient interview and questionnaire
- Evidence of formation of anti-HLA antibodies [ Time Frame: Baseline, 6 months, 12 months ]change from baseline to 6 and 12 months post infusion as measured by PRA testing
- Incidence of graft vs. host disease [ Time Frame: Baseline through 12 months ]cumulative incidence as measured by patient interview and questionnaire
- Incidence of unexpected adverse events, by severity and relation to study [ Time Frame: Baseline through 12 months ]cumulative incidence as measured by patient questionnaire and clinical labs
- The Vineland Adaptive Behavior Scale Interview, 3rd Edition, Comprehensive interview form [ Time Frame: Baseline and 6 months ]Change from baseline to six months in the Combined Socialization Standard Score based on parent report. Scores range from 20 to 140. Higher scores indicate a higher functioning level
- Social Responsiveness Scale, Second Edition (SRS-2) [ Time Frame: Baseline and 6 months ]Change from baseline to six months of the Communication Score calculated from the parent/guardian questionnaire. The SRS-2 provides a continuous measure of social ability. Scores range from 40 to >= 90, with higher scores indicating greater social impairment.
- Social Withdrawal Subscale of the Aberrant Behavior Checklist, Community Edition (ABC-C) [ Time Frame: Baseline and 6 months ]Change from baseline to six months based on parent/guardian questionnaire. Scores range from 0-48. Higher scores indicate that behaviors in the subscale occur with higher frequency.
- Repetitive Behavior Scale Revised - parent/guardian questionnaire [ Time Frame: Baseline and 6 months ]
Change from baseline to six months based on parent report.
- Stereotyped Behavior Subscale: 0 to 18
- Self-Injurious behavior subscale: 0 to 24
- Compulsive Behavior subscale: 0 to 24
- Ritualistic behavior subscale: 0 to 19
- Sameness Behavior subscale: 0 to 33
- Restricted Behavior subscale: 0 to 12
The higher the score the more the behavior occurs and the greater a problem it is.
- Pediatric Quality of Life Inventory General Core Scales [ Time Frame: Baseline and 6 months ]Change from baseline to six months based on parent report. Scores range from 0 to 100 and higher scores indicate a better Health-Related Quality of Life, or better functioning.
- Pediatric Quality of Life Inventory Family Impact Measure [ Time Frame: Baseline and 6 months ]Change from baseline to six months based on parent report. Scores range from 0-100 and higher scores indicate better functioning.
- Pediatric Quality of Life Inventory General Core Scales - Adult Version [ Time Frame: Baseline and 6 months ]Change from baseline to six months based on self report. Scores range from 0-100 and higher scores indicate a better Health-Related Quality of Life or better functioning.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04484077
|Contact: Sydney Crane, RNfirstname.lastname@example.org|
|Contact: Lettie Mooreemail@example.com|
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Contact: Jessica Sun, RN 919-684-3401 firstname.lastname@example.org|
|Principal Investigator:||Jessica Sun, MD||Duke University|
|Principal Investigator:||Joanne Kurtzberg, MD||Duke University|
|Principal Investigator:||Geraldine Dawson, PhD||Duke Health|