Efficacy of Allogeneic Umbilical Cord Derived Hematopoietic and Mesenchymal Stem Cells in Cerebral Palsy

NCT ID: NCT03795974

Last Updated: 2019-01-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 108 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-23
• Study Completion Date: 2019-12-31

Brief Summary

Cerebral palsy(CP) consisted of a group of developmental disability in the field of motor function and is one of the major problems of pediatric neurology and at the present time there is no standard curative medical or surgical treatment for it .Stem cell therapy is one of a new and hopeful therapeutic methods of therapy for CP .This double blind study designed for the evaluation of safety and therapeutic effects of intrathecal hematopoietic and mesenchymal stem cells derived from allogenic umbilical cord in change and probable improvement of developmental functions of spastic CP participants between 4-14 years old and comparing with control group of CP participants without cell therapy . 108 cases recruited and randomly divided to 3 groups of 36 cases : hematopoietic stem cells derived from allogenic umbilical cord , Mesenchymal cells derived from allogenic umbilical cord and control group without injection and appearance simulating lumbar puncture without awareness of the patients and evaluators . Developmental functions and spasticity evaluated before intervention and will be done 1 , 3 , 6 and 12 months after injection . During this period neuro rehabilitation will be continued . Brain neuroimaging were done at the recruitment time and will be repeated after 12 months .

Detailed Description

CP is characterized by aberrant control of movement or posture of a patient , appearing early in life , and not the result of a recognized progressive or degenerative brain disease . CP is an umbrella term and represents a group of conditions (not a single disorder) , has a broad range of expression with a static condition originally within the developing central nervous system . CP Is a disturbance of movement and or posture . At the present time there is no standard medical or surgical treatment for it .Stem cell therapy is a new and promising treatment .

150 cases of diparetic and quadiparetic spastic CP between 4-14 years old selected among the patients referred to the pediatric neurology outpatient department of Children's Medical Center Hospital (CMC) affiliated to Tehran University of Medical Sciences and had our inclusion criteria. HLA analysis were done for these patients and 36 cases of class 6 matched cases enrolled to the hematopoietic stem cells derived from allogenic umbilical cord (MNC) because of necessity of Human Leukocyte Antigen (HLA) matching in this type of cells and 72 cases among the remaining patients randomly divided to Mesenchymal stem cells derived from allogenic umbilical cord (MSC) and control group . Therefore 108 cases enrolled in 3 divided group of 36 patients .

Patients admitted to CMC hospital and intrathecal injection were done with sedation . Only one injection of stem cell was done for each patient . In the control group after insertion of the needle into the skin with an appearance of lumbar puncture simulation , no injection were done without the awareness of the patients or their parents. All of the patients admitted for one day and discharged the next day . As we wrote in the consent form for ethical consideration we are committed to perform stem cell injection for control participants free of charge after 12 months of the follow up . All of the participants will be referred for neurorehabilitation with a identical protocol .Both parents and clinical evaluators are not aware of the 3 divided groups and our study is double blind .Outcome measures will be evaluated 1, 3, 6. and 12 months after intervention .

Standard brain Magnetic Resonance Imaging (MRI) with Magnetic Resonance Spectroscopy (MRS) and Diffusion Tensor Imaging (DTI) were done before injection as baseline and will be repeated after 12 months of clinical follow up . This study designed for the evaluation of therapeutic effects of intrathecal MNC and MSC derived from allogenic umbilical cord in change and probable improvement of developmental functions of spastic CP patients between 4-14 years old in comparison with control group .Different scoring systems such as Gross Motor Functional Classification System (GMFCS) , Gross Motor Function Measure Score (GMFM66) , Manual Ability Classification System (MACS) , Pediatric Evaluation of Disability Inventory (PEDI) , CP QOL , Life Habits Questionnaire and Modified Ashworth scale for spasticity were done at baseline and then will be repeated in follow ups until 12 months of final evaluation .

Acute side effects and probable long term side effects will be reported and noted on our preformed questioners .

Conditions

Cerebral Palsy, Spastic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

MNC & MSC with Control

One intrathecal injection of Hematopoietic stem cells and Mesenchymal stem cells derived from allogenic umbilical cord for each group of 36 cases of spastic CP and neurorehabilitation during the 12 months of follow up of clinical evaluation of developmental functions and spasticity

Group Type: ACTIVE_COMPARATOR

MNC

Intervention Type: BIOLOGICAL

Hematopoietic stem cells derived from allogenic umbilical cord

MSC

Intervention Type: BIOLOGICAL

Mesenchymal cells derived from allogenic umbilical cord

Control

Intervention Type: PROCEDURE

control group without injection and appearance simulating lumbar puncture without awareness of the patients and evaluators , but rehabilitation continued .

MNC & MSC

Comparison of effects of intrathecal injection of MNC and MSC on improvement of developmental functions and spasticity of CP patients

Group Type: EXPERIMENTAL

MNC

Intervention Type: BIOLOGICAL

Hematopoietic stem cells derived from allogenic umbilical cord

MSC

Intervention Type: BIOLOGICAL

Mesenchymal cells derived from allogenic umbilical cord

Interventions

MNC

Hematopoietic stem cells derived from allogenic umbilical cord

Intervention Type: BIOLOGICAL

MSC

Mesenchymal cells derived from allogenic umbilical cord

Intervention Type: BIOLOGICAL

Control

control group without injection and appearance simulating lumbar puncture without awareness of the patients and evaluators , but rehabilitation continued .

Intervention Type: PROCEDURE

Other Intervention Names

Hematopoietic stem cells; Mesenchymal stem cells

Eligibility Criteria

Inclusion Criteria

• Spastic cerebral palsy (Diparetic , Quadriparetic)
• Ages between 4 - 14 years
• Gross motor function classification ( GMFC) between 2 -5
• No seizure disorder or with controlled seizures
• Evidence of definite acquired abnormal imaging findings compatible with CP
• Informed consent is taken from their parents

Exclusion Criteria

• Normal brain MRI
• Progressive neurologic disorders
• Congenital cortical malformations
• TORCH infections (Toxoplasmosis,Other,Rubella,Cytomegalovirus and Herpes infections)
• Other types of cerebral palsy including athetoid , atonic , ataxic , and mixed type
• Acute intercurrent infections such as Hepatitis C Virus (HCV), Hepatitis B Virus (HBV), Human Immunodeficiency Virus (HIV) Malignancies
• Hemorrhagic diathesis
• Severe anemia ( Hemoglobin less than 8 g/dl )
• Ventilator dependent pulmonary diseases
• Renal insufficiency
• Severe liver dysfunction

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 14 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hormozgan University of Medical Sciences

OTHER

Sponsor Role: collaborator

Tehran University of Medical Sciences

OTHER

Sponsor Role: lead

Responsible Party

Mahmoud Reza Ashrafi

Professor of Pediatric Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mahmoudreza Ashrafi, MD

Role: PRINCIPAL_INVESTIGATOR

Tehran University of Medical Sciences, Children's Medical Center

Amirali Hamidieh, MD

Role: STUDY_DIRECTOR

Tehran University of Medical Sciences , Children's Medical Center

Hadi Montazerlotfelahi, MD

Role: STUDY_DIRECTOR

Alborz University of Medical Sciences

Anahita Majma, MD

Role: STUDY_DIRECTOR

Tehran University of Medical Sciences Children's Medical Center

Masood Ghahvechi akbari, MD

Role: STUDY_DIRECTOR

Tehran University of Medical Sciences ,Children's Medical Center

Ali Reza Moaeidi, MD

Role: STUDY_DIRECTOR

Hormozgan University of Medical Sciences

Locations

Tehran University of Medical Sciences , Growth and Development Research Center- Children's Medical Center

Tehran, , Iran

Tehran University of Medical Sciences Chidren's Medical Center Radiology Department

Tehran, , Iran

Tehran University of Medical Sciences, Department of Pediatric Neurology , Children's Medical Center

Tehran, , Iran

ROYAN Stem Cell Technology Co

Tehran, , Iran

Countries

Iran

References

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Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRCT201706176907N13

Identifier Type: -

Identifier Source: org_study_id