Mechanism of Allogeneic UCB Therapy in Cerebral Palsy

Phase 1

Completed

• Conditions: Cerebral Palsy; Child Development
• Interventions: Biological: allogeneic cord blood transplantation

• Registration Number: NCT03130816
• Lead Sponsor: Bundang CHA Hospital

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 available

Study Timeline

• Study Start: 2015-07-29
• Study First Submitted: 2017-04-20
• Study First Submitted QC: 2017-04-23
• Study First Posted: 2017-04-27
• Primary Completion: 2019-05-21
• Study Completion: 2019-05-21
• Status Verified: 2020-11
• Last Update Submitted: 2020-11-02
• Last Update Posted: 2020-11-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 90

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
allogeneic cord blood transplantation	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.

Primary Outcome Measures

Name	Time	Method
Change of GMFM	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.

Secondary Outcome Measures

Name	Time	Method
Change of mRNA assay	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	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.

Trial Locations

Locations (1)

CHA Bundang Medical Center; 🇰🇷 Seongnam, Gyeonggido, Korea, Republic of