Clinical trial NCT03795974: Efficacy of Allogeneic Umbilical Cord Derived Hematopoietic and Mesenchymal Stem Cells in Cerebral Palsy
Official title: Evaluation of the Efficacy of Allogeneic Umbilical Cord Derived Hematopoietic Stem Cells and Mesenchymal Stromal Cells in Patients With Spastic Cerebral Palsy on Developmental Function , A Clinical Trial phase2
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Cerebral Palsy, Spastic
Keywords: Quadriparetic CP, Diparetic CP, Spastic
Lead sponsor: Tehran University of Medical Sciences
Sponsor class: OTHER
Collaborators: name: Hormozgan University of Medical Sciences
First posted: 2019-01-08
Enrollment: 108
Sex: ALL
Minimum age (years): 4
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: HLA typing were done for 150 cases of spastic CP with our inclusion criteria and 36 cases of class 6 matching of HLA selected for hematopoietic stem cells derived from allogenic umbilical cord and 72 cases were randomly divided to Mesenchymal cells derived from allogenic umbilical cord and control group .
Primary purpose: TREATMENT

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 .

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

Primary outcomes:
measure: Change from baseline Gross Motor Function Classification System (GMFCS)
timeFrame: Baseline
measure: Change from baseline Gross Motor Function Classification System (GMFCS)
timeFrame: "month" 3
measure: Change from baseline Gross Motor Function Classification System (GMFCS)
timeFrame: "month" 6
measure: Change from baseline Gross Motor Function Classification System (GMFCS)
timeFrame: "month" 12
measure: Change from baseline GROSS MOTOR FUNCTION MEASURE (GMFM66)
timeFrame: Baseline
measure: Change from baseline GROSS MOTOR FUNCTION MEASURE (GMFM66)
timeFrame: "month" 1
measure: Change from baseline GROSS MOTOR FUNCTION MEASURE (GMFM66)
timeFrame: "month" 3
measure: Change from baseline GROSS MOTOR FUNCTION MEASURE (GMFM66)
timeFrame: "month" 6
measure: Change from baseline GROSS MOTOR FUNCTION MEASURE (GMFM66)
timeFrame: "month" 12
measure: Change from baseline Manual Ability Classification System for Children with Cerebral Palsy (MACS)
timeFrame: Baseline
measure: Change from baseline Manual Ability Classification System for Children with Cerebral Palsy (MACS)
timeFrame: "month" 3
measure: Change from baseline Manual Ability Classification System for Children with Cerebral Palsy (MACS)
timeFrame: "month" 6
measure: Change from baseline Manual Ability Classification System for Children with Cerebral Palsy (MACS)
timeFrame: "month" 12
measure: Change from baseline Pediatric Evaluation of Disability Inventory (PEDI)
timeFrame: Baseline
measure: Change from baseline Pediatric Evaluation of Disability Inventory (PEDI)
timeFrame: "month" 6
measure: Change from baseline Pediatric Evaluation of Disability Inventory (PEDI)
timeFrame: "month" 12
measure: Change from baseline Modified Ashworth scale
timeFrame: Baseline
measure: Change from baseline Modified Ashworth scale
timeFrame: "month" 1
measure: Change from baseline Modified Ashworth scale
timeFrame: "month" 3
measure: Change from baseline Modified Ashworth scale
timeFrame: "month" 6
measure: Change from baseline Modified Ashworth scale
timeFrame: "month" 12
Secondary outcomes:
measure: Change from baseline acquired Brain Magnetic Resonance Imaging (MRI) findings
timeFrame: Baseline
measure: Change from baseline acquired Brain Magnetic Resonance Imaging (MRI) findings
timeFrame: "month" 12
measure: Change from baseline Brain Magnetic Resonance Spectroscopy (MRS)
timeFrame: Baseline
measure: Change from baseline Brain Magnetic Resonance Spectroscopy (MRS)
timeFrame: "month" 12
measure: Change from baseline Diffuse Tensor Imaging (DTI) fiber count of periventricular white matter
timeFrame: Baseline
measure: Change from baseline Diffuse Tensor Imaging (DTI) fiber count of periventricular white matter
timeFrame: "month" 12
Other outcomes:
Locations:
city: Tehran
country: Iran, Islamic Republic of
facility: Tehran University of Medical Sciences , Growth and Development Research Center- Children's Medical Center
city: Tehran
country: Iran, Islamic Republic of
facility: Tehran University of Medical Sciences Chidren's Medical Center Radiology Department
city: Tehran
country: Iran, Islamic Republic of
facility: Tehran University of Medical Sciences, Department of Pediatric Neurology , Children's Medical Center
city: Tehran
country: Iran, Islamic Republic of
facility: ROYAN Stem Cell Technology Co
Study officials:
affiliation: Tehran University of Medical Sciences, Children's Medical Center
name: Mahmoudreza Ashrafi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tehran University of Medical Sciences , Children's Medical Center
name: Amirali Hamidieh, MD
role: STUDY_DIRECTOR
affiliation: Alborz University of Medical Sciences
name: Hadi Montazerlotfelahi, MD
role: STUDY_DIRECTOR
affiliation: Tehran University of Medical Sciences Children's Medical Center
name: Anahita Majma, MD
role: STUDY_DIRECTOR
affiliation: Tehran University of Medical Sciences ,Children's Medical Center
name: Masood Ghahvechi akbari, MD
role: STUDY_DIRECTOR
affiliation: Hormozgan University of Medical Sciences
name: Ali Reza Moaeidi, MD
role: STUDY_DIRECTOR
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