Autologous Cord Blood Stem Cells for Autism

• ClinicalTrials.gov Identifier: NCT01638819
• Recruitment Status: Completed
• First Posted: July 12, 2012
• Results First Posted: August 20, 2018
• Last Update Posted: August 20, 2018
• Sponsor: Sutter Health
• Information provided by (Responsible Party): Michael Chez, MD, Sutter Health

Tracking Information

• First Submitted Date: June 26, 2012
• First Posted Date: July 12, 2012
• Results First Submitted Date: May 1, 2018
• Results First Posted Date: August 20, 2018
• Last Update Posted Date: August 20, 2018
• Study Start Date: August 2012
• Actual Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 14, 2018)

Change in Language (Total Standard Score, Range 40 - 160) [ Time Frame: 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.

Original Primary Outcome Measures (submitted: July 9, 2012)

Change in language [ Time Frame: Baseline and 6 months ]

Change in language as measured by the Receptive One-Word Vocabulary Test (ROWVT) and Expressive One-Word Vocabulary Test (EOWVT) at baseline and six months following infusion of stem cells from AUCB or infusion of placebo.

Current Secondary Outcome Measures (submitted: August 14, 2018)

• Change in Behavior/Learning (Standard Score, Range 40 - 160 for Each Subtest) [ Time Frame: 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) [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: July 9, 2012)

• Improved Behavior/Learning [ Time Frame: Baseline and 6 months ]
  Change in the Vineland Adaptive Behavior Scales between baseline and six months after infusion of AUCB containing stem cells
• Improved Behavior [ Time Frame: Baseline and 6 months ]
  Change in Pervasive Developmental Disorders Behavior Index (PDDBI) between baseline and six months after infusion of AUCB containing stem cells
• Change in Serum Values [ Time Frame: Baseline and 6 months ]
  Change in the following between baseline and six months after infusion of AUCB containing stem cells as measured by: • Serum (TNF) alpha, Interleukin 1-alpha (IL-1α), interleukin 13( IL-13), Interleukin -1β, Interleukins 6, 10, 13

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Autologous Cord Blood Stem Cells for Autism
• Official Title: A Randomized, Blinded, Placebo-controlled, Crossover Study to Assess the Efficacy of Stem Cells From Autologous Umbilical Cord Blood to Improve Language and Behavior in Children With Autism

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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Autism

Intervention

• Biological: Autologous Cord Blood Stem Cells
  One infusion of 60 ml syringe of study product
• Biological: Placebo
  Saline

Study Arms

• Experimental: Autologous Cord Blood Stem Cells
  Intervention: Biological: Autologous Cord Blood Stem Cells
• Placebo Comparator: Placebo
  Saline
  Intervention: Biological: Placebo

• Publications *: Mauron A. [Autism, stem cells, and magical powder]. Rev Med Suisse. 2012 Sep 19;8(354):1795. No abstract available. French.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 9, 2012): 30
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: December 2016
• Actual Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Years to 7 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01638819
• Other Study ID Numbers: CB2011Chez
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Michael Chez, MD, Sutter Health
• Original Responsible Party: Same as current
• Current Study Sponsor: Sutter Health
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Michael Chez, MD; Sutter Health

• PRS Account: Sutter Health
• Verification Date: August 2018