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Mechanism of Allogeneic UCB Therapy in Cerebral Palsy

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ClinicalTrials.gov Identifier: NCT03130816
Recruitment Status : Active, not recruiting
First Posted : April 27, 2017
Last Update Posted : March 12, 2019
Sponsor:
Information provided by (Responsible Party):
Min Young Kim, MD, PhD, Bundang CHA Hospital

Tracking Information
First Submitted Date  ICMJE April 20, 2017
First Posted Date  ICMJE April 27, 2017
Last Update Posted Date March 12, 2019
Actual Study Start Date  ICMJE July 29, 2015
Estimated Primary Completion Date July 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 23, 2017)
Change of GMFM [ Time Frame: Baseline before UCB administration, months 3, 6, and 12 after UCB treatment ]
Gross motor function measure measured at baseline before UCB administration is compared to the score measured at months 3, 6, and 12 after UCB treatment.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03130816 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 23, 2017)
  • Change of mRNA assay [ Time Frame: Change between the baseline level before UCB therapy and levels after UCB administration at 2 days, 1 week, 5 weeks, and 12 months ]
    Separate peripheral blood mononuclear cell (PBMC) from the patients' blood sample and screen for changes in protein enzymes including those related to DUB at the mRNA level after UCB therapy.
  • Change of GMPM [ Time Frame: Baseline before UCB administration, months 3, 6, and 12 after UCB treatment ]
    Dissociated Movement, Coordination, Alignment, Weight shift, and Stability are rated with GMPM (Gross Motor Performance Measure). Each raw score (1-5 point) and converted percent scores are evaluated. Total score is 100(%), higher scores indicate better function. GMPM measured at baseline before UCB administration is compared to the score measured at months 3, 6, and 12 after UCB treatment.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Mechanism of Allogeneic UCB Therapy in Cerebral Palsy
Official Title  ICMJE Mechanism of Allogeneic Umbilical Cord Blood Therapy in Cerebral Palsy
Brief Summary

In our prior study on the therapeutic mechanism of UCB, changes in cytokine levels were observed but the results are inconclusive and further studies on animal models and changes of protein expression before and after UCB therapy in the clinical settings are required.

The changes in protein expression will be assessed by multiplex RT-PCR mRNA assay. Clinical efficacy of UCB therapy will be evaluated with various functional assessment tools. Factors regarding UCB therapy (number of transplanted cells, HLA matching status, serum level of immunosuppressant, etc.) and patient factors (age, functional status, etc.) will be analyzed for correlation with protein expression after UCB therapy. Several target proteins for analysis are available. Pentraxin and toll-like receptor (TLR) 4 are receptors modulating intrinsic immune reaction and was shown to have a significant correlation with clinical efficacy of stem cell therapy. Ubiquitine is a regulatory protein that combines with the target protein and affects its degradation, interaction, localization and activation. The ubiquitine system controls total protein quantity for homeostasis and can be found in all tissues. Deubiquitination (DUB) enzyme down-regulates this ubiquitine and is known to modulate all cellular changes

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Intervention Model Description:
Patients diagnosed with cerebral palsy volunteered for participation in this study.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Cerebral Palsy
  • Child Development
Intervention  ICMJE Biological: allogeneic cord blood transplantation
UCB with total nucleated cell count ≤ 7x108/kg will be used for this clinical trial. Suitable UCB (i.e., containing total nucleated cell count ≥2x107/kg with three or less mismatch among HLA-A, -B, and -DR) will be selected. This criterion was selected upon the rationale that even though minimal HLA mismatch is preferred, prior studies indicate significant effects of UCB therapy for patients with 3 HLA mismatches.
Study Arms  ICMJE Experimental: allogeneic cord blood transplantation

Intravenous(IV) infusion will be done by the following method A. After 4 hours of fasting, subjects will be sedated with chloral hydrate (Pocral®) syrup B. Intravenous infusion will be conducted in stem cell center, CHA Bundang Medical Center and the therapy will be performed by the Principal Investigator or a physician delegated from the Principal Investigator. The physician conducting the infusion will not participate in the efficacy and result analysis of this study.

C. Oxygen saturation will be monitored during therapy.

Intervention: Biological: allogeneic cord blood transplantation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: April 23, 2017)
90
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2019
Estimated Primary Completion Date July 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Diagnosed with cerebral palsy
  2. Age of ≥10 months and ≤20 years
  3. Mismatch in HLA-A, B, and DR ≤3, and total nucleated cell count ≥2x107/kg. If the cell count is less than given values, more than 2 units may be used.
  4. Voluntary decision to participation in the study with informed consent agreed and obtained from the subject's representative.
  5. Patient and/or representatives are both willing and capable of being hospitalized according to the schedule specified in the protocol and continue the study for 12 months after study entry.
  6. If the patient has participated in another clinical trial, at least 3 months should have passed since end of the study.

Exclusion Criteria:

  1. Current aspiration pneumonia
  2. Known genetic disease
  3. History of hypersensitivity reaction to any study drugs pertinent to the study
  4. Patient with severe convulsion disease who has clinical convulsion despite combination therapy with 3 or more agents
  5. Uncontrolled hypertension defined as systolic blood pressure >115 mmHg and/or diastolic blood pressure >70 mmHg
  6. Hepatic impairment defined as asparate aminotransferase (AST) >55 IU/L and/or alanine aminotrasferase (ALT) >45 IU/L
  7. Renal impairment defined as creatinine (Cr) ≥1.3 mg/dL
  8. Presence of diagnosed or suspected malignant tumor and/or hematologic malignancy
  9. Non-compliance with study visits specified in the protocol or poor compliance of care-giver.
  10. Any factors not specified above that the principal investigator determines medically inadequate for participation in this study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 10 Months to 20 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Korea, Republic of
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03130816
Other Study ID Numbers  ICMJE 2015-06-093
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Min Young Kim, MD, PhD, Bundang CHA Hospital
Study Sponsor  ICMJE Bundang CHA Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: MinYoung Kim, MD, PhD CHA University
PRS Account Bundang CHA Hospital
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP