Efficacy of Intravenous Umbilical Cord Blood Infusion as Cell Therapy for Children With Autism Spectrum Disorder (ASD): Duke ACT
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 180
- 试验地点
- 2
- 主要终点
- Change in Social Communication as Measured by the Vineland Adaptive Behavior Scales, Third Edition (VABS-3)
研究概览
简要总结
This is a single site, prospective, randomized, double-blind study of a single intravenous autologous or allogeneic, unrelated cord blood (CB) infusion in children ages 2-7 years with Autism Spectrum Disorder (ASD). Participants will be randomly assigned to Sequence A, consisting of a single infusion of CB cells at baseline followed 6 months later by a single infusion of placebo, or Sequence B, consisting of an infusion of placebo at baseline followed 6 months later by an infusion of CB cells. All participants will ultimately be treated with CB cells at some point during the study. Participants with an available qualified autologous CB unit will receive autologous cells, and those without a suitable autologous CB unit available will receive cells from a ≥4/6 HLA-matched, ABO-matched allogeneic, unrelated donor CB unit from the Carolinas Cord Blood Bank. All infusions will be double-blinded. The primary outcomes will be assessed 6 months after the initial infusion in the sequence. Additional testing for secondary exploratory analyses will be performed at 12 months. Duration of study participation will be 12 months from the time of baseline infusion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 2 Years 至 7 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 2 years to ≤ 7 years (7 years, 364 days) at the time of visit 1
- •Confirmed clinical DSM-5 diagnosis of Autism Spectrum Disorder using the DSM-5 Checklist
- •Fragile X testing performed and negative
- •Available and qualified umbilical cord blood unit with a minimum banked total nucleated cell dose of ≥ 2.5 x 107 cells/kg that meets criteria outlined in Section 6.0, either:
- •Autologous umbilical cord blood unit OR
- •≥4/6 HLA-matched and ABO/Rh-matched allogeneic unrelated umbilical cord blood unit from the Carolinas Cord Blood Bank
- •Stable on current psychiatric medication regimen (dose and dosing schedule) for at least 2 months prior to infusion of study product
- •Normal absolute lymphocyte count (≥1500/uL)
- •Participant and parent/guardian are English speaking
- •Able to travel to Duke University two times (baseline and 6 months post-baseline), and parent/guardian is able to participate in interim surveys and interviews
- •Parental consent
排除标准
- •Review of medical records indicates ASD diagnosis not likely
- •Known diagnosis of any of the following coexisting psychiatric conditions: depression, bipolar disorder, schizophrenia, obsessive compulsive disorder, Tourette syndrome
- •Screening data suggests that participant would not be able to comply with the requirements of the study procedures, including study outcome measures, as assessed by the study team
- •Family is unwilling or unable to commit to participation in all study-related assessments, including follow up for approximately 12 months
- •Sibling is enrolled in this (DukeACT) study
- •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 b. Known pathogenic copy number variation (CNV) associated with ASD (e.g., 16p11.2, 15q13.2, 2q13.3)
- •Infectious:
- •Known active central nervous system infection
- •Evidence of uncontrolled infection based on records or clinical assessment
- •HIV positivity
- •Known metabolic disorder
- •Known mitochondrial dysfunction
- •History of unstable epilepsy or uncontrolled seizure disorder, infantile spasms, Lennox Gastaut syndrome, Dravet syndrome, or other similar chronic seizure disorder
- •Active malignancy or prior malignancy that was treated with chemotherapy
- •History of a primary immunodeficiency disorder
- •History of autoimmune cytopenias (i.e., ITP, AIHA)
- •Coexisting medical condition that would place the child at increased risk for complications of sedation or other study procedures
- •Concurrent genetic or acquired disease or comorbidity(ies) that could require a future stem cell transplant
- •Significant sensory (e.g., blindness, deafness, uncorrected hearing impairment) or motor (e.g., cerebral palsy) impairment
- •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
- •Significant hematologic abnormalities defined as: Hemoglobin <10.0 g/dL, White blood count < 3,000 cells/mL, absolute lymphocyte count <1000/uL, Platelets <150 x 10e9/uL
- •Evidence of clinically relevant physical dysmorphology indicative of a genetic syndrome as assessed by the PIs or other investigators, including a medical geneticist or psychiatrists trained in identifying dysmorphic features associated with neurodevelopmental conditions
- •Current/Prior Therapy:
- •History of prior cell therapy
- •Current or prior use of immune globulins or other anti-inflammatory medications with the exception of non steroidal anti-inflammatory medications
- •Current or prior immunosuppressive therapy
- •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.
结局指标
主要结局
Change in Social Communication as Measured by the Vineland Adaptive Behavior Scales, Third Edition (VABS-3)
时间窗: Baseline, 6 months
The Vineland Adaptive Behavior Scales, Third Edition (VABS-3) Socialization domain standard score has mean=100 and standard deviation=15 (range: 20-140). Higher scores indicate better developed adaptive social behavior. The change in the Socialization domain standard score was calculated for each participant from Baseline to Month 6. Changes in the Socialization standard score are indicative of skill acquisition relative to chronologically aged peers of the same sex. Thus, a zero (no change) represents change consistent with what is expected. An increase represents acquisition of more skills over time than would be expected. Participants who experience a decrease in Socialization standard score may still have acquired skills although not at the rate expected based on their age and sex.
次要结局
- Change in Pervasive Developmental Disorder Behavior Inventory (PDD-BI) Composite Standard Score (Parent Questionnaire)(Baseline, 6 months)
- Change in Clinical Global Impressions - Severity of Illness (CGI-S) Score, Clinician Assessment(Baseline, 6 months)
- Change in Expressive One-Word Picture Vocabulary Test (Clinician Assessment)(Baseline, 6 months)
- Clinical Global Impressions - Global Improvement (CGI-I) Score, Clinician Assessment(Baseline, 6 months)
- Change in Pervasive Developmental Disorder Behavior Inventory (PDD-BI) Repetitive, Ritualistic and Pragmatic Problems T-Score(Baseline, Month 6)
- Change in PDD-BI Sensory/Perceptual Approach Behaviors T-Score(Baseline, Month 6)
- Change in PDD-BI Ritualisms/Resistance to Change T-Score(Baseline, Month 6)
- Number of Participants With Infusion Reactions(12 months)
- Severity of Product-related Infections(12 months)
- Change in Vineland Socialization Domain Raw Score(Baseline, 6 months)
- Change in Vineland Socialization Domain Age Equivalent(Baseline, 6 months)
- Change in Vineland Adaptive Behavior Scales II (VABS-II) Communication Subscale Standard Score(Baseline, 6 months)
- Change in PDD-BI Social Pragmatic Problems T-Score(Baseline, Month 6)
- Change in PDD-BI Semantic/Pragmatic Problems T-Score(Baseline, Month 6)
- Change in Vineland Adaptive Behavior Scales II (VABS-II) Composite Score(Baseline, 6 months)
- Change in PDD-BI Arousal Regulation Problems T-Score(Baseline, Month 6)
- Change in PDD-BI Receptive/Expressive Social Communication Ability T-Score(Baseline, Month 6)
- Number of Participants With Product-related Infections(12 months)
- Evidence of Alloimmunization Via Anti-HLA (Human Leukocyte Antigen) and Anti-RBC (Red Blood Cell) Antibodies and Nonspecific Markers of Systemic Inflammation (ESR, CRP)(12 months)
- Severity of Graft vs. Host Disease(12 months)
- Incidence of Unexpected Adverse Events, by Relation to Study Product(6 months,12 months)
- Change in Vineland Adaptive Behavior Scales II (VABS-II) Daily Living Subscale Standard Score(Baseline, 6 months)
- Change in PDD-BI Approach/Withdrawal Problems T-Score(Baseline, Month 6)
- Change in PDD-BI Specific Fears T-Score(Baseline, Month 6)
- Incidence of Graft vs. Host Disease(12 months)
- Change in PDD-BI Aggressiveness T-Score(Baseline, Month 6)
- Change in PDD-BI Expressive Social Communication Abilities T-Score(Baseline, Month 6)
- Change in PDD-BI Social Approach Behaviors T-Score(Baseline, Month 6)
- Severity of Infusion Reactions(12 months)
- Change in PDD-BI Expressive Language T-Score(Baseline, Month 6)
- Change in PDD-BI Learning, Memory, and Receptive Language T-Score(Baseline, Month 6)
- Severity of Unexpected Adverse Events, by Relation to Study Product(6 months, 12 months)
研究者
Joanne Kurtzberg, MD
Chief Scientific Officer, Robertson Clinical and Translational Cell Therapy Program; Director, Pediatric Blood and Marrow Transplant Program and Carolinas Cord Blood Bank
Duke University