Clinical trial NCT03130816: Mechanism of Allogeneic UCB Therapy in Cerebral Palsy
Official title: Mechanism of Allogeneic Umbilical Cord Blood Therapy in Cerebral Palsy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Cerebral Palsy
Child Development
Keywords: Umbilical cord blood transplantation
Cytokine changes
Lead sponsor: Bundang CHA Hospital
Sponsor class: OTHER
First posted: 2017-04-27
Enrollment: 90
Sex: ALL
Minimum age (years): 10
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Patients diagnosed with cerebral palsy volunteered for participation in this study.
Primary purpose: TREATMENT

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


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.

Primary outcomes:
measure: Change of GMFM
timeFrame: Baseline before UCB administration, months 3, 6, and 12 after UCB treatment
Secondary outcomes:
measure: Change of mRNA assay
timeFrame: Change between the baseline level before UCB therapy and levels after UCB administration at 2 days, 1 week, 5 weeks, and 12 months
measure: Change of GMPM
timeFrame: Baseline before UCB administration, months 3, 6, and 12 after UCB treatment
Other outcomes:
Locations:
city: Seongnam
country: Korea, Republic of
facility: CHA Bundang Medical Center
state: Gyeonggido
Study officials:
affiliation: CHA University
name: MinYoung Kim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: