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Mechanism of Allogeneic UCB Therapy in Cerebral Palsy

Primary Purpose

Cerebral Palsy, Child Development

Status

Completed

Phase

Phase 1

Locations

Korea, Republic of

Study Type

Interventional

Intervention

allogeneic cord blood transplantation

About this trial

This is an interventional treatment trial for Cerebral Palsy focused on measuring Umbilical cord blood transplantation, Cytokine changes

Eligibility Criteria

10 Months - 20 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Diagnosed with cerebral palsy
Age of ≥10 months and ≤20 years
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.
Voluntary decision to participation in the study with informed consent agreed and obtained from the subject's representative.
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.
If the patient has participated in another clinical trial, at least 3 months should have passed since end of the study.

Exclusion Criteria:

Current aspiration pneumonia
Known genetic disease
History of hypersensitivity reaction to any study drugs pertinent to the study
Patient with severe convulsion disease who has clinical convulsion despite combination therapy with 3 or more agents
Uncontrolled hypertension defined as systolic blood pressure >115 mmHg and/or diastolic blood pressure >70 mmHg
Hepatic impairment defined as asparate aminotransferase (AST) >55 IU/L and/or alanine aminotrasferase (ALT) >45 IU/L
Renal impairment defined as creatinine (Cr) ≥1.3 mg/dL
Presence of diagnosed or suspected malignant tumor and/or hematologic malignancy
Non-compliance with study visits specified in the protocol or poor compliance of care-giver.
Any factors not specified above that the principal investigator determines medically inadequate for participation in this study.

Sites / Locations

CHA Bundang Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

allogeneic cord blood transplantation

Arm Description

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.

Outcomes

Primary Outcome Measures

Change of GMFM

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

Change of mRNA assay

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

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.

Full Information

NCT ID

NCT03130816

First Posted

April 20, 2017

Last Updated

November 2, 2020

Sponsor

Bundang CHA Hospital

1. Study Identification

Unique Protocol Identification Number

NCT03130816

Brief Title

Mechanism of Allogeneic UCB Therapy in Cerebral Palsy

Official Title

Mechanism of Allogeneic Umbilical Cord Blood Therapy in Cerebral Palsy

Study Type

Interventional

2. Study Status

Record Verification Date

November 2020

Overall Recruitment Status

Completed

Study Start Date

July 29, 2015 (Actual)

Primary Completion Date

May 21, 2019 (Actual)

Study Completion Date

May 21, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Bundang CHA Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cerebral Palsy, Child Development

Keywords

Umbilical cord blood transplantation, Cytokine changes

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Model Description

Patients diagnosed with cerebral palsy volunteered for participation in this study.

Masking

None (Open Label)

Allocation

N/A

Enrollment

90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

allogeneic cord blood transplantation

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

allogeneic cord blood transplantation

Intervention Description

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.

Primary Outcome Measure Information:

Title

Change of GMFM

Description

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.

Time Frame

Baseline before UCB administration, months 3, 6, and 12 after UCB treatment

Secondary Outcome Measure Information:

Title

Change of mRNA assay

Description

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.

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

Title

Change of GMPM

Description

Time Frame

Baseline before UCB administration, months 3, 6, and 12 after UCB treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

10 Months

Maximum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Diagnosed with cerebral palsy Age of ≥10 months and ≤20 years 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. Voluntary decision to participation in the study with informed consent agreed and obtained from the subject's representative. 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. If the patient has participated in another clinical trial, at least 3 months should have passed since end of the study. Exclusion Criteria: Current aspiration pneumonia Known genetic disease History of hypersensitivity reaction to any study drugs pertinent to the study Patient with severe convulsion disease who has clinical convulsion despite combination therapy with 3 or more agents Uncontrolled hypertension defined as systolic blood pressure >115 mmHg and/or diastolic blood pressure >70 mmHg Hepatic impairment defined as asparate aminotransferase (AST) >55 IU/L and/or alanine aminotrasferase (ALT) >45 IU/L Renal impairment defined as creatinine (Cr) ≥1.3 mg/dL Presence of diagnosed or suspected malignant tumor and/or hematologic malignancy Non-compliance with study visits specified in the protocol or poor compliance of care-giver. Any factors not specified above that the principal investigator determines medically inadequate for participation in this study.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

MinYoung Kim, MD, PhD

Organizational Affiliation

CHA University

Official's Role

Principal Investigator

Facility Information:

Facility Name

CHA Bundang Medical Center

City

Seongnam

State/Province

Gyeonggido

ZIP/Postal Code

13496

Country

Korea, Republic of

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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Mechanism of Allogeneic UCB Therapy in Cerebral Palsy

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