Mechanism of Allogeneic UCB Therapy in Cerebral Palsy

NCT ID: NCT03130816

Last Updated: 2020-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-29
• Study Completion Date: 2019-05-21

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

Conditions

Cerebral Palsy; Child Development

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

allogeneic cord blood transplantation

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

• Minimum Eligible Age: 10 Months
• Maximum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bundang CHA Hospital

OTHER

Sponsor Role: lead

Responsible Party

MinYoung Kim, MD, PhD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

MinYoung Kim, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

CHA University

Locations

CHA Bundang Medical Center

Seongnam, Gyeonggido, South Korea

Countries

South Korea

References

Suh MR, Min K, Cho KH, Kim J, Lim I, Park M, Noh EM, Kim MY. Maintenance of the synergistic effects of cord blood cells and erythropoietin combination therapy after additional cord blood infusion in children with cerebral palsy: 1-year open-label extension study of randomized placebo-controlled trial. Stem Cell Res Ther. 2023 Dec 12;14(1):362. doi: 10.1186/s13287-023-03600-4.

Reference Type: DERIVED

PMID: 38087394 (View on PubMed)

Other Identifiers

2015-06-093

Identifier Type: -

Identifier Source: org_study_id