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

Cerebral Palsy, Spastic Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03795974
• Other study ID #: IRCT201706176907N13
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 23, 2017
• Est. completion date: December 2019

Study information

• Verified date: January 2019
• Source: Tehran University of Medical Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 .

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 .

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 108
• Est. completion date: December 2019
• Est. primary completion date: October 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 14 Years

Eligibility

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

Related Conditions & MeSH terms

• Cerebral Palsy
• Cerebral Palsy, Spastic
• Muscle Spasticity

Intervention

Biological:
• MNC
Hematopoietic stem cells derived from allogenic umbilical cord
• MSC
Mesenchymal cells derived from allogenic umbilical cord

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

Locations

Country	Name	City	State
Iran, Islamic Republic of	ROYAN Stem Cell Technology Co	Tehran
Iran, Islamic Republic of	Tehran University of Medical Sciences , Growth and Development Research Center- Children's Medical Center	Tehran
Iran, Islamic Republic of	Tehran University of Medical Sciences Chidren's Medical Center Radiology Department	Tehran
Iran, Islamic Republic of	Tehran University of Medical Sciences, Department of Pediatric Neurology , Children's Medical Center	Tehran

Sponsors (2)

Lead Sponsor	Collaborator
Tehran University of Medical Sciences	Hormozgan University of Medical Sciences

Country where clinical trial is conducted

Iran, Islamic Republic of, 

References & Publications (10)

Ashwal S, Russman BS, Blasco PA, Miller G, Sandler A, Shevell M, Stevenson R; Quality Standards Subcommittee of the American Academy of Neurology; Practice Committee of the Child Neurology Society. Practice parameter: diagnostic assessment of the child wi — View Citation

Bax M, Goldstein M, Rosenbaum P, Leviton A, Paneth N, Dan B, Jacobsson B, Damiano D; Executive Committee for the Definition of Cerebral Palsy. Proposed definition and classification of cerebral palsy, April 2005. Dev Med Child Neurol. 2005 Aug;47(8):571-6 — View Citation

Crompton KE, Elwood N, Kirkland M, Clark P, Novak I, Reddihough D. Feasibility of trialling cord blood stem cell treatments for cerebral palsy in Australia. J Paediatr Child Health. 2014 Jul;50(7):540-4. doi: 10.1111/jpc.12618. Epub 2014 Jun 9. — View Citation

Feng M, Lu A, Gao H, Qian C, Zhang J, Lin T, Zhao Y. Safety of Allogeneic Umbilical Cord Blood Stem Cells Therapy in Patients with Severe Cerebral Palsy: A Retrospective Study. Stem Cells Int. 2015;2015:325652. doi: 10.1155/2015/325652. Epub 2015 Jul 8. — View Citation

Papadopoulos KI, Low SS, Aw TC, Chantarojanasiri T. Safety and feasibility of autologous umbilical cord blood transfusion in 2 toddlers with cerebral palsy and the role of low dose granulocyte-colony stimulating factor injections. Restor Neurol Neurosci. 2011;29(1):17-22. doi: 10.3233/RNN-2011-0572. — View Citation

Romanov YA, Svintsitskaya VA, Smirnov VN. Searching for alternative sources of postnatal human mesenchymal stem cells: candidate MSC-like cells from umbilical cord. Stem Cells. 2003;21(1):105-10. — View Citation

Shevell MI, Dagenais L, Hall N; REPACQ CONSORTIUM*. The relationship of cerebral palsy subtype and functional motor impairment: a population-based study. Dev Med Child Neurol. 2009 Nov;51(11):872-7. doi: 10.1111/j.1469-8749.2009.03269.x. Epub 2009 Mar 11. — View Citation

Thomas B, Eyssen M, Peeters R, Molenaers G, Van Hecke P, De Cock P, Sunaert S. Quantitative diffusion tensor imaging in cerebral palsy due to periventricular white matter injury. Brain. 2005 Nov;128(Pt 11):2562-77. Epub 2005 Jul 27. — View Citation

Wang X, Cheng H, Hua R, Yang J, Dai G, Zhang Z, Wang R, Qin C, An Y. Effects of bone marrow mesenchymal stromal cells on gross motor function measure scores of children with cerebral palsy: a preliminary clinical study. Cytotherapy. 2013 Dec;15(12):1549-6 — View Citation

Zali A, Arab L, Ashrafi F, Mardpour S, Niknejhadi M, Hedayati-Asl AA, Halimi-Asl A, Ommi D, Hosseini SE, Baharvand H, Aghdami N. Intrathecal injection of CD133-positive enriched bone marrow progenitor cells in children with cerebral palsy: feasibility and — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline Gross Motor Function Classification System (GMFCS)	The Gross Motor Function Classification System (GMFCS) for cerebral palsy is based on self-initiated movement, with emphasis on sitting, transfers, and mobility. When defining a five-level classification system, our primary criterion has been that the distinctions between levels must be meaningful in daily life. Distinctions are based on functional limitations, the need for hand-held mobility devices (such as walkers, crutches, or canes) or wheeled mobility, and to a much lesser extent, 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 We enrolled the patients with GMFCS more than class II and evaluate for change of this scale during the follow up period . Lower scores demonstrate better gross motor function of children .	Baseline
Primary	Change from baseline Gross Motor Function Classification System (GMFCS)	The Gross Motor Function Classification System (GMFCS) for cerebral palsy is based on self-initiated movement, with emphasis on sitting, transfers, and mobility. When defining a five-level classification system, our primary criterion has been that the distinctions between levels must be meaningful in daily life. Distinctions are based on functional limitations, the need for hand-held mobility devices (such as walkers, crutches, or canes) or wheeled mobility, and to a much lesser extent, 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 We enrolled the patients with GMFCS more than class II and evaluate for change of this scale during the follow up period . Lower scores demonstrate better gross motor function of children .	"month" 3
Primary	Change from baseline Gross Motor Function Classification System (GMFCS)	The Gross Motor Function Classification System (GMFCS) for cerebral palsy is based on self-initiated movement, with emphasis on sitting, transfers, and mobility. When defining a five-level classification system, our primary criterion has been that the distinctions between levels must be meaningful in daily life. Distinctions are based on functional limitations, the need for hand-held mobility devices (such as walkers, crutches, or canes) or wheeled mobility, and to a much lesser extent, 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 We enrolled the patients with GMFCS more than class II and evaluate for change of this scale during the follow up period . Lower scores demonstrate better gross motor function of children .	"month" 6
Primary	Change from baseline Gross Motor Function Classification System (GMFCS)	The Gross Motor Function Classification System (GMFCS) for cerebral palsy is based on self-initiated movement, with emphasis on sitting, transfers, and mobility. When defining a five-level classification system, our primary criterion has been that the distinctions between levels must be meaningful in daily life. Distinctions are based on functional limitations, the need for hand-held mobility devices (such as walkers, crutches, or canes) or wheeled mobility, and to a much lesser extent, 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 We enrolled the patients with GMFCS more than class II and evaluate for change of this scale during the follow up period . Lower scores demonstrate better gross motor function of children .	"month" 12
Primary	Change from baseline GROSS MOTOR FUNCTION MEASURE (GMFM66)	The GMFM is a standardized observational instrument designed and validated to measure change in gross motor function over time in children with cerebral palsy.; GMFM 66 contained 66 item and each item include 4 score (0-3) SCORING KEY 0 = does not initiate 1 = initiates 2 = partially completes 3 = completes We are using validated Persian version of GMFM 66 in this research. Higher scores demonstrate better gross motor function of children.	Baseline
Primary	Change from baseline GROSS MOTOR FUNCTION MEASURE (GMFM66)	The GMFM is a standardized observational instrument designed and validated to measure change in gross motor function over time in children with cerebral palsy.; GMFM 66 contained 66 item and each item include 4 score (0-3) SCORING KEY 0 = does not initiate 1 = initiates 2 = partially completes 3 = completes We are using validated Persian version of GMFM 66 in this research. Higher scores demonstrate better gross motor function of children.	"month" 1
Primary	Change from baseline GROSS MOTOR FUNCTION MEASURE (GMFM66)	The GMFM is a standardized observational instrument designed and validated to measure change in gross motor function over time in children with cerebral palsy.; GMFM 66 contained 66 item and each item include 4 score (0-3) SCORING KEY 0 = does not initiate 1 = initiates 2 = partially completes 3 = completes We are using validated Persian version of GMFM 66 in this research. Higher scores demonstrate better gross motor function of children.	"month" 3
Primary	Change from baseline GROSS MOTOR FUNCTION MEASURE (GMFM66)	The GMFM is a standardized observational instrument designed and validated to measure change in gross motor function over time in children with cerebral palsy.; GMFM 66 contained 66 item and each item include 4 score (0-3) SCORING KEY 0 = does not initiate 1 = initiates 2 = partially completes 3 = completes We are using validated Persian version of GMFM 66 in this research. Higher scores demonstrate better gross motor function of children.	"month" 6
Primary	Change from baseline GROSS MOTOR FUNCTION MEASURE (GMFM66)	The GMFM is a standardized observational instrument designed and validated to measure change in gross motor function over time in children with cerebral palsy.; GMFM 66 contained 66 item and each item include 4 score (0-3) SCORING KEY 0 = does not initiate 1 = initiates 2 = partially completes 3 = completes We are using validated Persian version of GMFM 66 in this research. Higher scores demonstrate better gross motor function of children.	"month" 12
Primary	Change from baseline Manual Ability Classification System for Children with Cerebral Palsy (MACS)	The Manual Ability Classification System (MACS)describes how children with cerebral palsy (CP)use their hands to handle objects in daily activities.; MACS describes five levels. The levels are based on the children's self-initiated ability to handle objects and their need for assistance or adaptation to perform manual activities in everyday life.; Handle objects easily and successfully; Handles most objects but with somewhat reduced quality and/or speed of achievement; Handle objects with difficulty; needs help to prepare and/or modify activities; Handles a limited selection of easily managed objects in adapted situations; Does not handle objects and has severely limited ability to perform even simple actions Level I include children with minor limitations, while children with severe functional limitations will usually be found at levels IV and V.; We are using validated Persian classification system.	Baseline
Primary	Change from baseline Manual Ability Classification System for Children with Cerebral Palsy (MACS)	The Manual Ability Classification System (MACS)describes how children with cerebral palsy (CP)use their hands to handle objects in daily activities.; MACS describes five levels. The levels are based on the children's self-initiated ability to handle objects and their need for assistance or adaptation to perform manual activities in everyday life.; Handle objects easily and successfully; Handles most objects but with somewhat reduced quality and/or speed of achievement; Handle objects with difficulty; needs help to prepare and/or modify activities; Handles a limited selection of easily managed objects in adapted situations; Does not handle objects and has severely limited ability to perform even simple actions Level I include children with minor limitations, while children with severe functional limitations will usually be found at levels IV and V.; We are using validated Persian classification system.	"month" 3
Primary	Change from baseline Manual Ability Classification System for Children with Cerebral Palsy (MACS)	The Manual Ability Classification System (MACS)describes how children with cerebral palsy (CP)use their hands to handle objects in daily activities.; MACS describes five levels. The levels are based on the children's self-initiated ability to handle objects and their need for assistance or adaptation to perform manual activities in everyday life.; Handle objects easily and successfully; Handles most objects but with somewhat reduced quality and/or speed of achievement; Handle objects with difficulty; needs help to prepare and/or modify activities; Handles a limited selection of easily managed objects in adapted situations; Does not handle objects and has severely limited ability to perform even simple actions Level I include children with minor limitations, while children with severe functional limitations will usually be found at levels IV and V.; We are using validated Persian classification system.	"month" 6
Primary	Change from baseline Manual Ability Classification System for Children with Cerebral Palsy (MACS)	The Manual Ability Classification System (MACS)describes how children with cerebral palsy (CP)use their hands to handle objects in daily activities.; MACS describes five levels. The levels are based on the children's self-initiated ability to handle objects and their need for assistance or adaptation to perform manual activities in everyday life.; Handle objects easily and successfully; Handles most objects but with somewhat reduced quality and/or speed of achievement; Handle objects with difficulty; needs help to prepare and/or modify activities; Handles a limited selection of easily managed objects in adapted situations; Does not handle objects and has severely limited ability to perform even simple actions Level I include children with minor limitations, while children with severe functional limitations will usually be found at levels IV and V.; We are using validated Persian classification system.	"month" 12
Primary	Change from baseline Pediatric Evaluation of Disability Inventory (PEDI)	The PEDI contains items to measure functional capability, and also items to measure the performance in three content domains: Self Care (SC), Mobility (M) and Social Function (SF), Capability is measured by the assessment of the functional skills of which the child has shown mastery.; The items in the FSS are discrete and are accompanied by scoring criteria and sometimes examples of behavior to help clarify scoring decisions. The items can be scored 0 or 1. 0 = unable or limited in capability to perform item in most situations 1 = capable of performing item in most situations, or item has been previously mastered and functional skills have progressed beyond this level.; We are using validated Persian version of this Questionnaire. Higher scores demonstrate better functional capability.	Baseline
Primary	Change from baseline Pediatric Evaluation of Disability Inventory (PEDI)	The PEDI contains items to measure functional capability, and also items to measure the performance in three content domains: Self Care (SC), Mobility (M) and Social Function (SF), Capability is measured by the assessment of the functional skills of which the child has shown mastery.; The items in the FSS are discrete and are accompanied by scoring criteria and sometimes examples of behavior to help clarify scoring decisions. The items can be scored 0 or 1. 0 = unable or limited in capability to perform item in most situations 1 = capable of performing item in most situations, or item has been previously mastered and functional skills have progressed beyond this level.; We are using validated Persian version of this Questionnaire. Higher scores demonstrate better functional capability.	"month" 6
Primary	Change from baseline Pediatric Evaluation of Disability Inventory (PEDI)	The PEDI contains items to measure functional capability, and also items to measure the performance in three content domains: Self Care (SC), Mobility (M) and Social Function (SF), Capability is measured by the assessment of the functional skills of which the child has shown mastery.; The items in the FSS are discrete and are accompanied by scoring criteria and sometimes examples of behavior to help clarify scoring decisions. The items can be scored 0 or 1. 0 = unable or limited in capability to perform item in most situations 1 = capable of performing item in most situations, or item has been previously mastered and functional skills have progressed beyond this level.; We are using validated Persian version of this Questionnaire. Higher scores demonstrate better functional capability.	"month" 12
Primary	Change from baseline Modified Ashworth scale	Scoring (taken from Bohannon and Smith, 1987): 0 No increase in muscle tone; Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension 1+ Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM; More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved; Considerable increase in muscle tone, passive movement difficult; Affected part(s) rigid in flexion or extension ankle plantar flexion ,knee flexion ,hip flexion , wrist flexion , elbow flexion will be exam-ed by Modified Ashwotth scale and change in severity of spasticity; ankle plantar flexion,knee flexion,hip flexion,wrist flexion,elbow flexion,Spasticity improvement of patients according to Modified Ashworth scale	Baseline
Primary	Change from baseline Modified Ashworth scale	Scoring (taken from Bohannon and Smith, 1987): 0 No increase in muscle tone; Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension 1+ Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM; More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved; Considerable increase in muscle tone, passive movement difficult; Affected part(s) rigid in flexion or extension ankle plantar flexion ,knee flexion ,hip flexion , wrist flexion , elbow flexion will be exam-ed by Modified Ashwotth scale and change in severity of spasticity; ankle plantar flexion,knee flexion,hip flexion,wrist flexion,elbow flexion,Spasticity improvement of patients according to Modified Ashworth scale	"month" 1
Primary	Change from baseline Modified Ashworth scale	Scoring (taken from Bohannon and Smith, 1987): 0 No increase in muscle tone; Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension 1+ Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM; More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved; Considerable increase in muscle tone, passive movement difficult; Affected part(s) rigid in flexion or extension ankle plantar flexion ,knee flexion ,hip flexion , wrist flexion , elbow flexion will be exam-ed by Modified Ashwotth scale and change in severity of spasticity; ankle plantar flexion,knee flexion,hip flexion,wrist flexion,elbow flexion,Spasticity improvement of patients according to Modified Ashworth scale	"month" 3
Primary	Change from baseline Modified Ashworth scale	Scoring (taken from Bohannon and Smith, 1987): 0 No increase in muscle tone; Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension 1+ Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM; More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved; Considerable increase in muscle tone, passive movement difficult; Affected part(s) rigid in flexion or extension ankle plantar flexion ,knee flexion ,hip flexion , wrist flexion , elbow flexion will be exam-ed by Modified Ashwotth scale and change in severity of spasticity; ankle plantar flexion,knee flexion,hip flexion,wrist flexion,elbow flexion,Spasticity improvement of patients according to Modified Ashworth scale	"month" 6
Primary	Change from baseline Modified Ashworth scale	Scoring (taken from Bohannon and Smith, 1987): 0 No increase in muscle tone; Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension 1+ Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM; More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved; Considerable increase in muscle tone, passive movement difficult; Affected part(s) rigid in flexion or extension ankle plantar flexion ,knee flexion ,hip flexion , wrist flexion , elbow flexion will be exam-ed by Modified Ashwotth scale and change in severity of spasticity; ankle plantar flexion,knee flexion,hip flexion,wrist flexion,elbow flexion,Spasticity improvement of patients according to Modified Ashworth scale	"month" 12
Secondary	Change from baseline acquired Brain Magnetic Resonance Imaging (MRI) findings	One of our inclusion criteria for enrollment of the cases was evidence of definite acquired abnormal imaging findings compatible with CP such as periventricular leukomalacia (PVL) , cystic encephalomalacia ,periventricular gliosis , porencephalic cyst , basal ganglia involvement and brain atrophy . Decrements in size or improvement of Brain imaging findings would be expected due to Stem Cell therapy and will be followed 12 months after injection .	Baseline
Secondary	Change from baseline acquired Brain Magnetic Resonance Imaging (MRI) findings	One of our inclusion criteria for enrollment of the cases was evidence of definite acquired abnormal imaging findings compatible with CP such as periventricular leukomalacia (PVL) , cystic encephalomalacia ,periventricular gliosis , porencephalic cyst , basal ganglia involvement and brain atrophy . Decrements in size or improvement of Brain imaging findings would be expected due to Stem Cell therapy and will be followed 12 months after injection .	"month" 12
Secondary	Change from baseline Brain Magnetic Resonance Spectroscopy (MRS)	MRS allows noninvasive detection and measurement of normal and abnormal metabolites and biochemical changes in the brain . The frequency of different metabolites is measured in units called parts per million (PPM) and plotted on a graph as peaks of varying height . The metabolites normally detected in the brain, regardless of the adopted echo time, include Nacetyl aspartate (NAA),a neuronal marker, choline (Cho), a membrane marker, and creatine (Cr), an energy metabolism marker. Increase in NAA /Cr and NAA/Cho ratios expected as baseline and would be expected to have a change after Stem Cell therapy in favor of neuroglia cells load or number increase at the site of previous brain damage.	Baseline
Secondary	Change from baseline Brain Magnetic Resonance Spectroscopy (MRS)	MRS allows noninvasive detection and measurement of normal and abnormal metabolites and biochemical changes in the brain . The frequency of different metabolites is measured in units called parts per million (PPM) and plotted on a graph as peaks of varying height . The metabolites normally detected in the brain, regardless of the adopted echo time, include Nacetyl aspartate (NAA),a neuronal marker, choline (Cho), a membrane marker, and creatine (Cr), an energy metabolism marker. Increase in NAA /Cr and NAA/Cho ratios expected as baseline and would be expected to have a change after Stem Cell therapy in favor of neuroglia cells load or number increase at the site of previous brain damage.	"month" 12
Secondary	Change from baseline Diffuse Tensor Imaging (DTI) fiber count of periventricular white matter	DTI is a modi?cation of the MRI technique that is sensitive to the Brownian motion of water molecules in biological tissues and is a new clinical method that can demonstrate the orientation and integrity of white matter ?bers . Periventricular white matter injury is a major form of brain injury observed in CP . Signi?cant reduction in DTI ?ber count on the periventricular or other regions of cerebral white matter injury involving corticospinal tract , corticobulbar tract and superior thalamic radiation expected as baseline . Increase in DTI ?ber count would be expected due to Stem Cell therapy and will be followed 12 months after injection .	Baseline
Secondary	Change from baseline Diffuse Tensor Imaging (DTI) fiber count of periventricular white matter	DTI is a modi?cation of the MRI technique that is sensitive to the Brownian motion of water molecules in biological tissues and is a new clinical method that can demonstrate the orientation and integrity of white matter ?bers . Periventricular white matter injury is a major form of brain injury observed in CP . Signi?cant reduction in DTI ?ber count on the periventricular or other regions of cerebral white matter injury involving corticospinal tract , corticobulbar tract and superior thalamic radiation expected as baseline . Increase in DTI ?ber count would be expected due to Stem Cell therapy and will be followed 12 months after injection .	"month" 12