Mechanism of Allogeneic UCB Therapy in Cerebral Palsy

NCT03130816 | Completed Phase 1

• 1 other identifier: 2015-06-093
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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

Keywords

Umbilical cord blood transplantation; Cytokine changes

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (2)

• 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

• Change of GMPM

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

Study Arms (1)

allogeneic cord blood transplantation

EXPERIMENTAL

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.

Biological: allogeneic cord blood transplantation

Interventions

allogeneic cord blood transplantation 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.

allogeneic cord blood transplantation

Eligibility Criteria

• Age: 10 Months - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bundang CHA Hospital: lead

Study Sites (1)

CHA Bundang Medical Center

Seongnam, Gyeonggido, 13496, South Korea

Location

Related Publications (1)

• 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.

  PMID: 38087394 DERIVED

MeSH Terms

Conditions

Cerebral Palsy

Condition Hierarchy (Ancestors)

Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• MinYoung Kim, MD, PhD

  CHA University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

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

Study Record Dates

• First Submitted: April 20, 2017
• First Posted: April 27, 2017
• Study Start: July 29, 2015
• Primary Completion: May 21, 2019
• Study Completion: May 21, 2019
• Last Updated: November 4, 2020

Record last verified: 2020-11

Locations

KR (1)