Autism
Conditions
Brief summary
Evaluate the efficacy of one infusion of stem cells from autologous umbilical cord blood in patients with autism over six months after infusion as measured by changes in expressive and receptive language. Also demonstrate improved behavior, learning, and changes in Serum tumor necrosis factor alpha (TNF-α), tumor necrosis factor beta (TNF-β), interleukin 1-alpha (IL-1α), interleukin 1-beta (IL-1β), interleukin 6 (IL-6), interleukin 10 (IL-10), and interleukin 13 (IL-13).
Detailed description
This is a single-center, randomized, placebo-controlled, crossover outpatient study with 15 subjects receiving one infusion of autologous umbilical cord blood (AUCB) containing a minimum of 10 million total nucleated cells per kilogram (TNC/kg) and 15 subjects receiving an infusion of placebo (saline). After the 24-week follow-up testing is conducted, the groups will crossover so that patients who initially received AUCB will receive placebo and patients who received placebo at baseline will receive the cord blood. Both groups will be tested again 24-weeks after infusion. The neuropsychologist, PI, staff from Cord Blood Registry (CBR), and parents will be blinded as to the infusion sequence. The duration of participation for each study subject is approximately 55 weeks. This includes one screening visit over a period of approximately 6 weeks, one visit for baseline testing, one day for infusion of TNC (minimum 10 million/kg) or saline placebo followed by 24 weeks of follow-up. A second baseline visit is conducted at week-24 with the second infusion of TNC or saline placebo occurring 5-7 days after. Twenty-four additional weeks of follow-up occur after the second infusion.
Interventions
BIOLOGICALAutologous Cord Blood Stem Cells
One infusion of 60 ml syringe of study product
BIOLOGICALPlacebo
Saline
Sponsors
Sutter Health
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Years to 7 Years
Healthy volunteers
No
Inclusion criteria
* Age 2 to 7 years of age * Diagnosis of Autistic Disorder as diagnosed by the Diagnostic and Statistical Manual, 4th Edition, Text Revision (DSM-IV-TR) developmental delays, and ADOS * A sufficient quantity of autologous cord blood stored at Cord Blood Registry that was stored and processed using the Thermogenesis AutoXpress Platform * Stable on any current medications for at least 2 months prior to infusion of cord blood * Medical records indicating that patient does not have genetic conditions such as cerebral palsy, cystic fibrosis, muscular dystrophy, crohns disease, rheumatoid disease, fragile X, Retts Syndrome, Angelman Syndrome, tuberous sclerosis, epilepsy, or known genetic defects that overlap autism spectrum. * Results of an EEG within 12-months of baseline * English speaking
Exclusion criteria
* CNS infection * Extreme prematurity (\< 34 weeks gestation) * Severe Cognitive Disability IQ below 45 with autism * Clinical seizure activity within 6 months of baseline * Lennox Gastaut syndrome or infantile spasms * Dravet syndrome * HIV, renal or hepatic impairment * Prior hematological or malignant disease * Fever of 101 F within 2 weeks prior to infusion * Serious CNS infection or trauma * Unwilling to commit to follow-up * Mental illness including schizophrenia * Pervasive Developmental Disorder-Not Otherwise Specified * Asperger's Disorder * Cord blood unit is less than 85% viable, has a TNC of less than 10 million/kg, or sterility testing results are positive * Garlic allergy * Previous adverse reaction to Dimethyl Sulfoxide (DMSO) * Maternal medical records indicate communicable diseases including HIV, Hepatitis B or C, syphilis, cytomegalovirus (CMV) * Currently taking anti-inflammatory medications * History of asthma who may potentially require treatment with steroids * Inflammatory Disease * Renal/hepatic disease: serum Creatinine \> 1.5 mg/dl and total Bilirubin \> 1.5 mg/dl * Allergic to diphenhydramine (Benadryl) * Treatment with chelation therapy, hyperbaric oxygen therapy, pig worm therapy, or other alternative therapies the investigator deems clinically relevant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Language (Total Standard Score, Range 40 - 160) | Baseline and 6 months | Change in language as measured by the Receptive One-Word Vocabulary Test (ROWVT-4) and Expressive One-Word Vocabulary Test (EOWVT-4) at baseline and six months following infusion of stem cells from AUCB or infusion of placebo. The ROWPVT-4 and EOWPVT-4 were administered by a neuropsychologist and are norm-referenced assessments. The ROWPVT-4 tests an individual's ability to match a spoken word with an image of an object, action, or concept. The EOWPVT-4 tests an individual's ability to name, with one word, objects, actions, and concepts when presented with color illustrations. The tests target the ability to understand the meaning of words spoken and name what is depicted on a test plate without context. Scores of 85-115 are considered to be within the average range of functioning. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Behavior/Learning (Standard Score, Range 40 - 160 for Each Subtest) | Baseline and 6 months | Change in the Vineland Adaptive Behavior and Socialization Scales (2nd edition) between baseline and six months after infusion of AUCB containing stem cells. Vineland Adaptive Behavior and Socialization Scales consist of the following subparts: Daily Living Skills, Socialization, and Adaptive Behavior Composite (ABC). These are questionnaires completed by a parent or caregiver. Scores above 80 are classified using approximately the same ranges as IQ tests. Scores below 80 are categorized as borderline adaptive functioning (70-80); mildly deficient adaptive functioning (51-69); moderately deficient adaptive behavior (36-50); severely deficient adaptive behavior; (20-35); and markedly or profoundly deficient adaptive behavior (\<20). |
| Change in Knowledge and Fluid Reasoning (Scaled Score, Range 1-19 for Each Subtest) | Baseline and 6 months | The Stanford Binet, version 5, was used to assess the brain function. It can assess the level of intelligence across several age spans and ability levels. The Stanford-Binet looks at intelligence in five areas. In this study 2 areas were looked at: Knowledge and Fluid Reasoning that were age and condition appropriate. Each sub-test has a mean of 10 and a standard deviation of 3. The standard deviation indicates how far above or below the norm the subject's score is. Scores of 7 to 13 are considered to be within the average range of functioning. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Autologous Cord Blood Stem Cells First/Placebo Second Autologous Cord Blood Stem Cells: One infusion of 60 ml syringe of study product
Placebo: Saline | 14 |
| Placebo First/Autologous Cord Blood Stem Cells Second Autologous Cord Blood Stem Cells: One infusion of 60 ml syringe of study product
Placebo: Saline | 15 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Autologous Cord Blood Stem Cells First/Placebo Second | Total | Placebo First/Autologous Cord Blood Stem Cells Second |
|---|---|---|---|
| Abnormal EEG at baseline | 5 Participants | 9 Participants | 4 Participants |
| Age, Continuous | 4.50 years | 4.53 years | 4.57 years |
| Autism Diagnostic Observation Schedule (ADOS) | 7.93 units on a scale STANDARD_DEVIATION 1.39 | 7.24 units on a scale STANDARD_DEVIATION 2.5 | 6.60 units on a scale STANDARD_DEVIATION 3.14 |
| Compartment infused Large compartment (80%) | 9 Participants | 21 Participants | 12 Participants |
| Compartment infused Small compartment (20%) | 5 Participants | 8 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 5 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 24 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Percent viability post-thaw, (flow cytometry 7-AAD) | 51.36 Percent viable cells STANDARD_DEVIATION 11.36 | 53.73 Percent viable cells STANDARD_DEVIATION 11.37 | 55.75 Percent viable cells STANDARD_DEVIATION 11.38 |
| Percent viable CD34 (cluster of differentiation) - post-thaw | 49.54 Percent viable cells STANDARD_DEVIATION 36.66 | 47.30 Percent viable cells STANDARD_DEVIATION 36.41 | 45.06 Percent viable cells STANDARD_DEVIATION 37.46 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 12 Participants | 24 Participants | 12 Participants |
| Region of Enrollment United States | 14 participants | 29 participants | 15 participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 1 Participants |
| Sex: Female, Male Male | 11 Participants | 25 Participants | 14 Participants |
| TNC dose infused x 10^6/kg | 14.49 Number of cells infused x 10^6/kg STANDARD_DEVIATION 6.12 | 16.16 Number of cells infused x 10^6/kg STANDARD_DEVIATION 7.26 | 18.17 Number of cells infused x 10^6/kg STANDARD_DEVIATION 8.3 |
| Viable total nucleated cell (vTNC) count infused | 314.88 number of alive cells x 10^6/kg STANDARD_DEVIATION 236.52 | 335.09 number of alive cells x 10^6/kg STANDARD_DEVIATION 203.06 | 359.34 number of alive cells x 10^6/kg STANDARD_DEVIATION 163.22 |
| Weight | 19.79 kilograms (kg) STANDARD_DEVIATION 4.44 | 19.21 kilograms (kg) STANDARD_DEVIATION 3.75 | 18.67 kilograms (kg) STANDARD_DEVIATION 3.02 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 29 |
| other Total, other adverse events | 28 / 29 |
| serious Total, serious adverse events | 0 / 29 |
Outcome results
Primary
Change in Language (Total Standard Score, Range 40 - 160)
Change in language as measured by the Receptive One-Word Vocabulary Test (ROWVT-4) and Expressive One-Word Vocabulary Test (EOWVT-4) at baseline and six months following infusion of stem cells from AUCB or infusion of placebo. The ROWPVT-4 and EOWPVT-4 were administered by a neuropsychologist and are norm-referenced assessments. The ROWPVT-4 tests an individual's ability to match a spoken word with an image of an object, action, or concept. The EOWPVT-4 tests an individual's ability to name, with one word, objects, actions, and concepts when presented with color illustrations. The tests target the ability to understand the meaning of words spoken and name what is depicted on a test plate without context. Scores of 85-115 are considered to be within the average range of functioning.
Time frame: Baseline and 6 months
Population: Please note that endpoints for only the first 24 weeks were recorded due to the fact that the placebo second group may not be a true placebo group (stem cell infusion does not necessarily wash out like a drug).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Autologous Cord Blood Stem Cells | Change in Language (Total Standard Score, Range 40 - 160) | ROWPVT-4 baseline | 79.62 units on a scale | Standard Deviation 25.85 |
| Autologous Cord Blood Stem Cells | Change in Language (Total Standard Score, Range 40 - 160) | ROWPVT-4 6 months | 80.45 units on a scale | Standard Deviation 22.07 |
| Autologous Cord Blood Stem Cells | Change in Language (Total Standard Score, Range 40 - 160) | EOWPVT-4 baseline | 74.55 units on a scale | Standard Deviation 23.23 |
| Autologous Cord Blood Stem Cells | Change in Language (Total Standard Score, Range 40 - 160) | EOWPVT-4 6 months | 74.03 units on a scale | Standard Deviation 22 |
| Placebo | Change in Language (Total Standard Score, Range 40 - 160) | EOWPVT-4 6 months | 75.38 units on a scale | Standard Deviation 23.22 |
| Placebo | Change in Language (Total Standard Score, Range 40 - 160) | ROWPVT-4 baseline | 79.66 units on a scale | Standard Deviation 21.21 |
| Placebo | Change in Language (Total Standard Score, Range 40 - 160) | EOWPVT-4 baseline | 73.10 units on a scale | Standard Deviation 20.88 |
| Placebo | Change in Language (Total Standard Score, Range 40 - 160) | ROWPVT-4 6 months | 80.59 units on a scale | Standard Deviation 26.33 |
Secondary
Change in Behavior/Learning (Standard Score, Range 40 - 160 for Each Subtest)
Change in the Vineland Adaptive Behavior and Socialization Scales (2nd edition) between baseline and six months after infusion of AUCB containing stem cells. Vineland Adaptive Behavior and Socialization Scales consist of the following subparts: Daily Living Skills, Socialization, and Adaptive Behavior Composite (ABC). These are questionnaires completed by a parent or caregiver. Scores above 80 are classified using approximately the same ranges as IQ tests. Scores below 80 are categorized as borderline adaptive functioning (70-80); mildly deficient adaptive functioning (51-69); moderately deficient adaptive behavior (36-50); severely deficient adaptive behavior; (20-35); and markedly or profoundly deficient adaptive behavior (\<20).
Time frame: Baseline and 6 months
Population: Please note that endpoints for only the first 24 weeks were recorded due to the fact that the placebo second group may not be a true placebo group (stem cell infusion does not necessarily wash out like a drug).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Autologous Cord Blood Stem Cells | Change in Behavior/Learning (Standard Score, Range 40 - 160 for Each Subtest) | ABC - baseline | 66.00 units on a scale | Standard Deviation 12.2 |
| Autologous Cord Blood Stem Cells | Change in Behavior/Learning (Standard Score, Range 40 - 160 for Each Subtest) | ABC - 6 month | 67.57 units on a scale | Standard Deviation 16.52 |
| Autologous Cord Blood Stem Cells | Change in Behavior/Learning (Standard Score, Range 40 - 160 for Each Subtest) | Communication - baseline | 66.00 units on a scale | Standard Deviation 15.56 |
| Autologous Cord Blood Stem Cells | Change in Behavior/Learning (Standard Score, Range 40 - 160 for Each Subtest) | Communication - 6 month | 68.00 units on a scale | Standard Deviation 18.82 |
| Autologous Cord Blood Stem Cells | Change in Behavior/Learning (Standard Score, Range 40 - 160 for Each Subtest) | Motor - baseline | 73.86 units on a scale | Standard Deviation 13.17 |
| Autologous Cord Blood Stem Cells | Change in Behavior/Learning (Standard Score, Range 40 - 160 for Each Subtest) | Motor - 6 month | 69.71 units on a scale | Standard Deviation 15.1 |
| Autologous Cord Blood Stem Cells | Change in Behavior/Learning (Standard Score, Range 40 - 160 for Each Subtest) | Daily - baseline | 68.14 units on a scale | Standard Deviation 15.55 |
| Autologous Cord Blood Stem Cells | Change in Behavior/Learning (Standard Score, Range 40 - 160 for Each Subtest) | Daily - 6 month | 70.36 units on a scale | Standard Deviation 17.73 |
| Placebo | Change in Behavior/Learning (Standard Score, Range 40 - 160 for Each Subtest) | Daily - 6 month | 77.33 units on a scale | Standard Deviation 15.3 |
| Placebo | Change in Behavior/Learning (Standard Score, Range 40 - 160 for Each Subtest) | ABC - baseline | 74.27 units on a scale | Standard Deviation 16 |
| Placebo | Change in Behavior/Learning (Standard Score, Range 40 - 160 for Each Subtest) | Motor - baseline | 77.67 units on a scale | Standard Deviation 13.57 |
| Placebo | Change in Behavior/Learning (Standard Score, Range 40 - 160 for Each Subtest) | ABC - 6 month | 75.00 units on a scale | Standard Deviation 11.6 |
| Placebo | Change in Behavior/Learning (Standard Score, Range 40 - 160 for Each Subtest) | Daily - baseline | 77.13 units on a scale | Standard Deviation 16.61 |
| Placebo | Change in Behavior/Learning (Standard Score, Range 40 - 160 for Each Subtest) | Communication - baseline | 79.60 units on a scale | Standard Deviation 17.18 |
| Placebo | Change in Behavior/Learning (Standard Score, Range 40 - 160 for Each Subtest) | Motor - 6 month | 76.67 units on a scale | Standard Deviation 7.61 |
| Placebo | Change in Behavior/Learning (Standard Score, Range 40 - 160 for Each Subtest) | Communication - 6 month | 83.33 units on a scale | Standard Deviation 15.46 |
Secondary
Change in Knowledge and Fluid Reasoning (Scaled Score, Range 1-19 for Each Subtest)
The Stanford Binet, version 5, was used to assess the brain function. It can assess the level of intelligence across several age spans and ability levels. The Stanford-Binet looks at intelligence in five areas. In this study 2 areas were looked at: Knowledge and Fluid Reasoning that were age and condition appropriate. Each sub-test has a mean of 10 and a standard deviation of 3. The standard deviation indicates how far above or below the norm the subject's score is. Scores of 7 to 13 are considered to be within the average range of functioning.
Time frame: Baseline and 6 months
Population: Please note that endpoints for only the first 24 weeks were recorded due to the fact that the placebo second group may not be a true placebo group (stem cell infusion does not necessarily wash out like a drug).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Autologous Cord Blood Stem Cells | Change in Knowledge and Fluid Reasoning (Scaled Score, Range 1-19 for Each Subtest) | Fluid Reasoning - baseline | 5.86 units on a scale | Standard Deviation 5.46 |
| Autologous Cord Blood Stem Cells | Change in Knowledge and Fluid Reasoning (Scaled Score, Range 1-19 for Each Subtest) | Fluid Reasoning - 6 months | 6.79 units on a scale | Standard Deviation 5.75 |
| Autologous Cord Blood Stem Cells | Change in Knowledge and Fluid Reasoning (Scaled Score, Range 1-19 for Each Subtest) | Knowledge - baseline | 3.97 units on a scale | Standard Deviation 3.46 |
| Autologous Cord Blood Stem Cells | Change in Knowledge and Fluid Reasoning (Scaled Score, Range 1-19 for Each Subtest) | Knowledge - 6 months | 4.62 units on a scale | Standard Deviation 3.75 |
| Placebo | Change in Knowledge and Fluid Reasoning (Scaled Score, Range 1-19 for Each Subtest) | Knowledge - 6 months | 4.41 units on a scale | Standard Deviation 3.7 |
| Placebo | Change in Knowledge and Fluid Reasoning (Scaled Score, Range 1-19 for Each Subtest) | Fluid Reasoning - baseline | 5.97 units on a scale | Standard Deviation 5.28 |
| Placebo | Change in Knowledge and Fluid Reasoning (Scaled Score, Range 1-19 for Each Subtest) | Knowledge - baseline | 4.45 units on a scale | Standard Deviation 3.63 |
| Placebo | Change in Knowledge and Fluid Reasoning (Scaled Score, Range 1-19 for Each Subtest) | Fluid Reasoning - 6 months | 6.41 units on a scale | Standard Deviation 5.69 |