Estimation of the Safety and Efficiency Transfusion of HLA Matched CBU in Patients With CP

NCT04098029 | Unknown Phase 2

• 1 other identifier: CP-HLA2019
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Cerebral palsy is a disorder of movement and posture resulted from a non-progressive lesion or injury of the immature brain. It is a leading cause of childhood-onset disability. Many experimental animal studies have revealed that umbilical cord blood is useful to repair neurological injury in the brain. Based on many experimental studies, umbilical cord blood is suggested as a potential therapy for cerebral palsy. This protocol was developed based on the results of the previously approved protocol of the center NCT03826498 (Allogeneic cord blood transfusion in patients with infantile cerebral palsy), which showed high efficiency in the rehabilitation of patients. The present protocol is intended for revealing the dependence of the clinical effect on the degree of tissue compatibility of umbilical cord blood samples and the recipient

Conditions

Cerebral Palsy

Keywords

Cerebral palsy; CP; Cord Blood; Stem cells; HLA

Outcome Measures

Primary Outcomes (5)

• Number of participants with non-serious and serious adverse events

  Safety assessment such as adverse events will be registered. Adverse events will be monitored during all trial.

  1 year

• Gross Motor Function Classification System (GMFCS - ER) scale severity change

  Evaluation of the overall dynamics of treatment. GMFCS is a 5 level clinical classification system that describes the gross motor function of people with cerebral palsy on the basis of self-initiated movement abilities. Distinctions between levels are based on functional abilities; the need for walkers, crutches, wheelchairs, or canes/walking sticks; and to a much lesser extent, the actual quality of movement: Level I: Walks without Limitations Level II: Walks with Limitations Level III: Walks Using a Hand-Held Mobility Device Level IV: Self-Mobility with Limitations; May Use Powered Mobility Level V: Transported in a Manual Wheelchair The Evaluation of the results is carried out by comparing the primary and subsequent indications. Information will be collected from parents.

  Baseline, 6 month after first infusion, 6 month after second infusion (3 times)

• Changes in Standardized Gross Motor Function 66 (GMFM-66) Score for all child.

  GMFM (Gross Motor Function Measure) as a standardized measurement tool for assessing Gross Motor Function consisting of sub-scales; lying \& rolling, sitting, crawling \& kneeling, standing, walking, running \& jumping (range: 0\~100, a Higher value means better gross motor function). We reported changes in GMFM between each assessment time point. Categories of outcome table are baseline and values of just subtracting the latter raw scores from the former ones. This test will be acquired for all children.

  Baseline, 6 month after first infusion, 6 month after second infusion (3 times)

• Changes in The Infant Toddler Quality of Life Questionnaire for child above 3yrs.

  ITQOL - the 47-item short-form (ITQOL-SF47) developed for use in infants and toddlers from 2-months-to-5 years of age. Form scores physical, mental and social well being/ For each concept, item responses are scored, summed, and transformed on a scale from 0 (worst health) to 100 (best health). Changes in the completed questionnaire will be assessed. This test will be acquired for the child above 3yrs.

  Baseline, 6 month after first infusion, 6 month after second infusion (3 times)

• Changes in Ashworth scale score for all child.

  The Ashworth scale (AS) measures resistance during passive soft-tissue stretching and is used as a simple measure of spasticity scoring, where: 0\. No increase in tone; 1. A slight increase in tone giving catch when the limb is moved in flexion and extension; 2. A more marked increase in tone, but the limb is easily flexed; 3. Considerable increases in tone, passive movement difficult; 4. Limb rigid in flexion or extension. This test will be acquired for the child above 3yrs.

  Baseline, 6 month after first infusion, 6 month after second infusion (3 times)

Secondary Outcomes (3)

• Number of Participants with Chimerism (longevity) of infused cell

  Baseline, 6 month after first infusion

• The correlation between the concentration of CD14+ cells in the sample of UCB and the treatment effectiveness degree.

  1, 6 months (At each infusion)

• The correlation between the concentration of CD34+ cells in the UCB and the treatment effectiveness degree

  1, 6 months (At each infusion)

Study Arms (3)

Group 1 Low HLA compatibility

EXPERIMENTAL

The patients in the first group will receive two CBU of low-level HLA matched infusions within a 6-month interval. The low-level match is 3 or less HLA compatibility degree by A, B, DRB1 loci.

Biological: Low HLA group CBU infusion

Group 2 High HLA compatibility

EXPERIMENTAL

The patients in the second group will receive two CBU of high-level HLA matched infusions within a 6-month interval. The high-level match is 4 or more HLA compatibility degree by A, B, DRB1 loci.

Biological: High HLA group CBU infusion

Standard therapy

OTHER

Patients with standard therapy as a control group

Other: Standard therapy

Interventions

Low HLA group CBU infusion BIOLOGICAL

CB-MNC (Cord Blood Mononuclear Cells) infusion from different donors. One dose consists of 2-15х10\^7 cells per 1 kg of patient weight for each infusion. The protocol includes 2 infusions with an interval of 6-x months. HLA compatibility of CB is 3 or fewer by A, B, DRB1 loci.

Group 1 Low HLA compatibility

High HLA group CBU infusion BIOLOGICAL

CB-MNC (Cord Blood Mononuclear Cells) infusion from different donors. One dose consists of 2-15х10\^7 cells per 1 kg of patient weight for each infusion. The protocol includes 2 infusions with an interval of 6-x months. HLA compatibility of CB is 4 or more by A, B, DRB1 loci.

Group 2 High HLA compatibility

Standard therapy OTHER

The standard therapy can include drugs, special psychology training, etc.

Also known as: Control group

Standard therapy

Eligibility Criteria

• Age: 1 Year - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may not qualify if:

• Patient age up to 1 year, older than 12 years;
• The presence of the following diseases in history: heart failure in the stage of decompensation, anemia and other blood diseases;
• Decompensation of chronic and endocrinological diseases;
• Acute viral and bacterial infections during the acute clinical phase of the disease;
• HIV infection, hepatitis of B and C types;
• Oncological diseases, chemotherapy in the anamnesis;
• Tuberculosis;
• Confirmed genetic disorders;
• A severe form of intellectual disability as a concomitant disease (diagnosis can be ignored, according to the decision of the Medical Committee of the Center);

Sponsors & Collaborators

• State-Financed Health Facility "Samara Regional Medical Center Dinasty": lead
• INBIO, LLC: collaborator

Study Sites (1)

Medical Centre Dinasty

Samara, 443095, Russia

RECRUITING

MeSH Terms

Conditions

Cerebral Palsy

Interventions

Standard of Care; Control Groups

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Officials

• STANISLAV VOLCHKOV, MD, PhD

  Medical Centre Dinasty

  PRINCIPAL INVESTIGATOR

Central Study Contacts

STANISLAV VOLCHKOV, MD, PhD

CONTACT

+79608159408; ct@cordbank.ru

Olga Tyumina, M.D, PhD

CONTACT

centr123@bk.ru

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy director, Quality assurance director

Model Details: In total, the study will involve 150 patients in three groups. The first and second groups will receive infusions of umbilical cord blood hematopoietic cells, with varying degrees of selection for the genes of the HLA system. The third group will be the control group. In the control group, 50 patients with similar pathology will be examined, comparable in age, sex and degree of disorder of the type of "paracopies" against the background of standard therapy.

Study Record Dates

• First Submitted: September 17, 2019
• First Posted: September 20, 2019
• Study Start: September 1, 2019
• Primary Completion: December 26, 2023
• Study Completion: May 26, 2024
• Last Updated: January 18, 2023

Record last verified: 2023-01

Locations

RU (1)