<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03795974</url>
  </required_header>
  <id_info>
    <org_study_id>IRCT201706176907N13</org_study_id>
    <nct_id>NCT03795974</nct_id>
  </id_info>
  <brief_title>Efficacy of Allogeneic Umbilical Cord Derived Hematopoietic and Mesenchymal Stem Cells in Cerebral Palsy</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tehran University of Medical Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hormozgan University of Medical Sciences</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Tehran University of Medical Sciences</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Cerebral palsy(CP) consisted of a group of developmental disability in the field of motor&#xD;
      function and is one of the major problems of pediatric neurology and at the present time&#xD;
      there is no standard curative medical or surgical treatment for it .Stem cell therapy is one&#xD;
      of a new and hopeful therapeutic methods of therapy for CP .This double blind study designed&#xD;
      for the evaluation of safety and therapeutic effects of intrathecal hematopoietic and&#xD;
      mesenchymal stem cells derived from allogenic umbilical cord in change and probable&#xD;
      improvement of developmental functions of spastic CP participants between 4-14 years old and&#xD;
      comparing with control group of CP participants without cell therapy . 108 cases recruited&#xD;
      and randomly divided to 3 groups of 36 cases : hematopoietic stem cells derived from&#xD;
      allogenic umbilical cord , Mesenchymal cells derived from allogenic umbilical cord and&#xD;
      control group without injection and appearance simulating lumbar puncture without awareness&#xD;
      of the patients and evaluators . Developmental functions and spasticity evaluated before&#xD;
      intervention and will be done 1 , 3 , 6 and 12 months after injection . During this period&#xD;
      neuro rehabilitation will be continued . Brain neuroimaging were done at the recruitment time&#xD;
      and will be repeated after 12 months .&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      CP is characterized by aberrant control of movement or posture of a patient , appearing early&#xD;
      in life , and not the result of a recognized progressive or degenerative brain disease . CP&#xD;
      is an umbrella term and represents a group of conditions (not a single disorder) , has a&#xD;
      broad range of expression with a static condition originally within the developing central&#xD;
      nervous system . CP Is a disturbance of movement and or posture . At the present time there&#xD;
      is no standard medical or surgical treatment for it .Stem cell therapy is a new and promising&#xD;
      treatment .&#xD;
&#xD;
      150 cases of diparetic and quadiparetic spastic CP between 4-14 years old selected among the&#xD;
      patients referred to the pediatric neurology outpatient department of Children's Medical&#xD;
      Center Hospital (CMC) affiliated to Tehran University of Medical Sciences and had our&#xD;
      inclusion criteria. HLA analysis were done for these patients and 36 cases of class 6 matched&#xD;
      cases enrolled to the hematopoietic stem cells derived from allogenic umbilical cord (MNC)&#xD;
      because of necessity of Human Leukocyte Antigen (HLA) matching in this type of cells and 72&#xD;
      cases among the remaining patients randomly divided to Mesenchymal stem cells derived from&#xD;
      allogenic umbilical cord (MSC) and control group . Therefore 108 cases enrolled in 3 divided&#xD;
      group of 36 patients .&#xD;
&#xD;
      Patients admitted to CMC hospital and intrathecal injection were done with sedation . Only&#xD;
      one injection of stem cell was done for each patient . In the control group after insertion&#xD;
      of the needle into the skin with an appearance of lumbar puncture simulation , no injection&#xD;
      were done without the awareness of the patients or their parents. All of the patients&#xD;
      admitted for one day and discharged the next day . As we wrote in the consent form for&#xD;
      ethical consideration we are committed to perform stem cell injection for control&#xD;
      participants free of charge after 12 months of the follow up . All of the participants will&#xD;
      be referred for neurorehabilitation with a identical protocol .Both parents and clinical&#xD;
      evaluators are not aware of the 3 divided groups and our study is double blind .Outcome&#xD;
      measures will be evaluated 1, 3, 6. and 12 months after intervention .&#xD;
&#xD;
      Standard brain Magnetic Resonance Imaging (MRI) with Magnetic Resonance Spectroscopy (MRS)&#xD;
      and Diffusion Tensor Imaging (DTI) were done before injection as baseline and will be&#xD;
      repeated after 12 months of clinical follow up . This study designed for the evaluation of&#xD;
      therapeutic effects of intrathecal MNC and MSC derived from allogenic umbilical cord in&#xD;
      change and probable improvement of developmental functions of spastic CP patients between&#xD;
      4-14 years old in comparison with control group .Different scoring systems such as Gross&#xD;
      Motor Functional Classification System (GMFCS) , Gross Motor Function Measure Score (GMFM66)&#xD;
      , Manual Ability Classification System (MACS) , Pediatric Evaluation of Disability Inventory&#xD;
      (PEDI) , CP QOL , Life Habits Questionnaire and Modified Ashworth scale for spasticity were&#xD;
      done at baseline and then will be repeated in follow ups until 12 months of final evaluation&#xD;
      .&#xD;
&#xD;
      Acute side effects and probable long term side effects will be reported and noted on our&#xD;
      preformed questioners .&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">July 23, 2017</start_date>
  <completion_date type="Anticipated">December 2019</completion_date>
  <primary_completion_date type="Anticipated">October 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <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 .</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
    <masking_description>only one of the investigators knows the type of cell therapy for intervention group and simulation of intrathecal injection for control group .</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline Gross Motor Function Classification System (GMFCS)</measure>
    <time_frame>Baseline</time_frame>
    <description>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.&#xD;
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 .</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Gross Motor Function Classification System (GMFCS)</measure>
    <time_frame>&quot;month&quot; 3</time_frame>
    <description>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.&#xD;
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 .</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Gross Motor Function Classification System (GMFCS)</measure>
    <time_frame>&quot;month&quot; 6</time_frame>
    <description>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.&#xD;
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 .</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Gross Motor Function Classification System (GMFCS)</measure>
    <time_frame>&quot;month&quot; 12</time_frame>
    <description>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.&#xD;
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 .</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline GROSS MOTOR FUNCTION MEASURE (GMFM66)</measure>
    <time_frame>Baseline</time_frame>
    <description>The GMFM is a standardized observational instrument designed and validated to measure change in gross motor function over time in children with cerebral palsy.&#xD;
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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline GROSS MOTOR FUNCTION MEASURE (GMFM66)</measure>
    <time_frame>&quot;month&quot; 1</time_frame>
    <description>The GMFM is a standardized observational instrument designed and validated to measure change in gross motor function over time in children with cerebral palsy.&#xD;
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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline GROSS MOTOR FUNCTION MEASURE (GMFM66)</measure>
    <time_frame>&quot;month&quot; 3</time_frame>
    <description>The GMFM is a standardized observational instrument designed and validated to measure change in gross motor function over time in children with cerebral palsy.&#xD;
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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline GROSS MOTOR FUNCTION MEASURE (GMFM66)</measure>
    <time_frame>&quot;month&quot; 6</time_frame>
    <description>The GMFM is a standardized observational instrument designed and validated to measure change in gross motor function over time in children with cerebral palsy.&#xD;
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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline GROSS MOTOR FUNCTION MEASURE (GMFM66)</measure>
    <time_frame>&quot;month&quot; 12</time_frame>
    <description>The GMFM is a standardized observational instrument designed and validated to measure change in gross motor function over time in children with cerebral palsy.&#xD;
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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Manual Ability Classification System for Children with Cerebral Palsy (MACS)</measure>
    <time_frame>Baseline</time_frame>
    <description>The Manual Ability Classification System (MACS)describes how children with cerebral palsy (CP)use their hands to handle objects in daily activities.&#xD;
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.&#xD;
Handle objects easily and successfully&#xD;
Handles most objects but with somewhat reduced quality and/or speed of achievement&#xD;
Handle objects with difficulty; needs help to prepare and/or modify activities&#xD;
Handles a limited selection of easily managed objects in adapted situations&#xD;
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.&#xD;
We are using validated Persian classification system.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Manual Ability Classification System for Children with Cerebral Palsy (MACS)</measure>
    <time_frame>&quot;month&quot; 3</time_frame>
    <description>The Manual Ability Classification System (MACS)describes how children with cerebral palsy (CP)use their hands to handle objects in daily activities.&#xD;
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.&#xD;
Handle objects easily and successfully&#xD;
Handles most objects but with somewhat reduced quality and/or speed of achievement&#xD;
Handle objects with difficulty; needs help to prepare and/or modify activities&#xD;
Handles a limited selection of easily managed objects in adapted situations&#xD;
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.&#xD;
We are using validated Persian classification system.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Manual Ability Classification System for Children with Cerebral Palsy (MACS)</measure>
    <time_frame>&quot;month&quot; 6</time_frame>
    <description>The Manual Ability Classification System (MACS)describes how children with cerebral palsy (CP)use their hands to handle objects in daily activities.&#xD;
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.&#xD;
Handle objects easily and successfully&#xD;
Handles most objects but with somewhat reduced quality and/or speed of achievement&#xD;
Handle objects with difficulty; needs help to prepare and/or modify activities&#xD;
Handles a limited selection of easily managed objects in adapted situations&#xD;
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.&#xD;
We are using validated Persian classification system.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Manual Ability Classification System for Children with Cerebral Palsy (MACS)</measure>
    <time_frame>&quot;month&quot; 12</time_frame>
    <description>The Manual Ability Classification System (MACS)describes how children with cerebral palsy (CP)use their hands to handle objects in daily activities.&#xD;
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.&#xD;
Handle objects easily and successfully&#xD;
Handles most objects but with somewhat reduced quality and/or speed of achievement&#xD;
Handle objects with difficulty; needs help to prepare and/or modify activities&#xD;
Handles a limited selection of easily managed objects in adapted situations&#xD;
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.&#xD;
We are using validated Persian classification system.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Pediatric Evaluation of Disability Inventory (PEDI)</measure>
    <time_frame>Baseline</time_frame>
    <description>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.&#xD;
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.&#xD;
We are using validated Persian version of this Questionnaire. Higher scores demonstrate better functional capability.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Pediatric Evaluation of Disability Inventory (PEDI)</measure>
    <time_frame>&quot;month&quot; 6</time_frame>
    <description>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.&#xD;
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.&#xD;
We are using validated Persian version of this Questionnaire. Higher scores demonstrate better functional capability.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Pediatric Evaluation of Disability Inventory (PEDI)</measure>
    <time_frame>&quot;month&quot; 12</time_frame>
    <description>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.&#xD;
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.&#xD;
We are using validated Persian version of this Questionnaire. Higher scores demonstrate better functional capability.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Modified Ashworth scale</measure>
    <time_frame>Baseline</time_frame>
    <description>Scoring (taken from Bohannon and Smith, 1987):&#xD;
0 No increase in muscle tone&#xD;
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&#xD;
More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved&#xD;
Considerable increase in muscle tone, passive movement difficult&#xD;
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&#xD;
ankle plantar flexion,knee flexion,hip flexion,wrist flexion,elbow flexion,Spasticity improvement of patients according to Modified Ashworth scale</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Modified Ashworth scale</measure>
    <time_frame>&quot;month&quot; 1</time_frame>
    <description>Scoring (taken from Bohannon and Smith, 1987):&#xD;
0 No increase in muscle tone&#xD;
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&#xD;
More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved&#xD;
Considerable increase in muscle tone, passive movement difficult&#xD;
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&#xD;
ankle plantar flexion,knee flexion,hip flexion,wrist flexion,elbow flexion,Spasticity improvement of patients according to Modified Ashworth scale</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Modified Ashworth scale</measure>
    <time_frame>&quot;month&quot; 3</time_frame>
    <description>Scoring (taken from Bohannon and Smith, 1987):&#xD;
0 No increase in muscle tone&#xD;
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&#xD;
More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved&#xD;
Considerable increase in muscle tone, passive movement difficult&#xD;
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&#xD;
ankle plantar flexion,knee flexion,hip flexion,wrist flexion,elbow flexion,Spasticity improvement of patients according to Modified Ashworth scale</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Modified Ashworth scale</measure>
    <time_frame>&quot;month&quot; 6</time_frame>
    <description>Scoring (taken from Bohannon and Smith, 1987):&#xD;
0 No increase in muscle tone&#xD;
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&#xD;
More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved&#xD;
Considerable increase in muscle tone, passive movement difficult&#xD;
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&#xD;
ankle plantar flexion,knee flexion,hip flexion,wrist flexion,elbow flexion,Spasticity improvement of patients according to Modified Ashworth scale</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline Modified Ashworth scale</measure>
    <time_frame>&quot;month&quot; 12</time_frame>
    <description>Scoring (taken from Bohannon and Smith, 1987):&#xD;
0 No increase in muscle tone&#xD;
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&#xD;
More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved&#xD;
Considerable increase in muscle tone, passive movement difficult&#xD;
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&#xD;
ankle plantar flexion,knee flexion,hip flexion,wrist flexion,elbow flexion,Spasticity improvement of patients according to Modified Ashworth scale</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline acquired Brain Magnetic Resonance Imaging (MRI) findings</measure>
    <time_frame>Baseline</time_frame>
    <description>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 .</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline acquired Brain Magnetic Resonance Imaging (MRI) findings</measure>
    <time_frame>&quot;month&quot; 12</time_frame>
    <description>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 .</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline Brain Magnetic Resonance Spectroscopy (MRS)</measure>
    <time_frame>Baseline</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline Brain Magnetic Resonance Spectroscopy (MRS)</measure>
    <time_frame>&quot;month&quot; 12</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline Diffuse Tensor Imaging (DTI) fiber count of periventricular white matter</measure>
    <time_frame>Baseline</time_frame>
    <description>DTI is a modiﬁcation 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 ﬁbers . Periventricular white matter injury is a major form of brain injury observed in CP . Signiﬁcant reduction in DTI ﬁber 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 ﬁber count would be expected due to Stem Cell therapy and will be followed 12 months after injection .</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline Diffuse Tensor Imaging (DTI) fiber count of periventricular white matter</measure>
    <time_frame>&quot;month&quot; 12</time_frame>
    <description>DTI is a modiﬁcation 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 ﬁbers . Periventricular white matter injury is a major form of brain injury observed in CP . Signiﬁcant reduction in DTI ﬁber 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 ﬁber count would be expected due to Stem Cell therapy and will be followed 12 months after injection .</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">108</enrollment>
  <condition>Cerebral Palsy, Spastic</condition>
  <arm_group>
    <arm_group_label>MNC &amp; MSC with Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>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</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MNC &amp; MSC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Comparison of effects of intrathecal injection of MNC and MSC on improvement of developmental functions and spasticity of CP patients</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>MNC</intervention_name>
    <description>Hematopoietic stem cells derived from allogenic umbilical cord</description>
    <arm_group_label>MNC &amp; MSC</arm_group_label>
    <arm_group_label>MNC &amp; MSC with Control</arm_group_label>
    <other_name>Hematopoietic stem cells</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>MSC</intervention_name>
    <description>Mesenchymal cells derived from allogenic umbilical cord</description>
    <arm_group_label>MNC &amp; MSC</arm_group_label>
    <arm_group_label>MNC &amp; MSC with Control</arm_group_label>
    <other_name>Mesenchymal stem cells</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Control</intervention_name>
    <description>control group without injection and appearance simulating lumbar puncture without awareness of the patients and evaluators , but rehabilitation continued .</description>
    <arm_group_label>MNC &amp; MSC with Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria :&#xD;
&#xD;
          -  Spastic cerebral palsy (Diparetic , Quadriparetic)&#xD;
&#xD;
          -  Ages between 4 - 14 years&#xD;
&#xD;
          -  Gross motor function classification ( GMFC) between 2 -5&#xD;
&#xD;
          -  No seizure disorder or with controlled seizures&#xD;
&#xD;
          -  Evidence of definite acquired abnormal imaging findings compatible with CP&#xD;
&#xD;
          -  Informed consent is taken from their parents&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Normal brain MRI&#xD;
&#xD;
          -  Progressive neurologic disorders&#xD;
&#xD;
          -  Congenital cortical malformations&#xD;
&#xD;
          -  TORCH infections (Toxoplasmosis,Other,Rubella,Cytomegalovirus and Herpes infections)&#xD;
&#xD;
          -  Other types of cerebral palsy including athetoid , atonic , ataxic , and mixed type&#xD;
&#xD;
          -  Acute intercurrent infections such as Hepatitis C Virus (HCV), Hepatitis B Virus&#xD;
             (HBV), Human Immunodeficiency Virus (HIV) Malignancies&#xD;
&#xD;
          -  Hemorrhagic diathesis&#xD;
&#xD;
          -  Severe anemia ( Hemoglobin less than 8 g/dl )&#xD;
&#xD;
          -  Ventilator dependent pulmonary diseases&#xD;
&#xD;
          -  Renal insufficiency&#xD;
&#xD;
          -  Severe liver dysfunction&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>4 Years</minimum_age>
    <maximum_age>14 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mahmoudreza Ashrafi, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Tehran University of Medical Sciences, Children's Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Amirali Hamidieh, MD</last_name>
    <role>Study Director</role>
    <affiliation>Tehran University of Medical Sciences , Children's Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Hadi Montazerlotfelahi, MD</last_name>
    <role>Study Director</role>
    <affiliation>Alborz University of Medical Sciences</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Anahita Majma, MD</last_name>
    <role>Study Director</role>
    <affiliation>Tehran University of Medical Sciences Children's Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Masood Ghahvechi akbari, MD</last_name>
    <role>Study Director</role>
    <affiliation>Tehran University of Medical Sciences ,Children's Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ali Reza Moaeidi, MD</last_name>
    <role>Study Director</role>
    <affiliation>Hormozgan University of Medical Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Tehran University of Medical Sciences , Growth and Development Research Center- Children's Medical Center</name>
      <address>
        <city>Tehran</city>
        <zip>1419733151</zip>
        <country>Iran, Islamic Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tehran University of Medical Sciences Chidren's Medical Center Radiology Department</name>
      <address>
        <city>Tehran</city>
        <zip>1419733151</zip>
        <country>Iran, Islamic Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tehran University of Medical Sciences, Department of Pediatric Neurology , Children's Medical Center</name>
      <address>
        <city>Tehran</city>
        <zip>1419733151</zip>
        <country>Iran, Islamic Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ROYAN Stem Cell Technology Co</name>
      <address>
        <city>Tehran</city>
        <zip>1665666311</zip>
        <country>Iran, Islamic Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Iran, Islamic Republic of</country>
  </location_countries>
  <reference>
    <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.</citation>
    <PMID>21335665</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>26236347</PMID>
  </reference>
  <reference>
    <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. doi: 10.1093/brain/awh600. Epub 2005 Jul 27.</citation>
    <PMID>16049045</PMID>
  </reference>
  <results_reference>
    <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 safety. Cytotherapy. 2015 Feb;17(2):232-41. doi: 10.1016/j.jcyt.2014.10.011. Epub 2014 Nov 1.</citation>
    <PMID>25593079</PMID>
  </results_reference>
  <results_reference>
    <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. doi: 10.1017/s001216220500112x.</citation>
    <PMID>16108461</PMID>
  </results_reference>
  <results_reference>
    <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.</citation>
    <PMID>19416339</PMID>
  </results_reference>
  <results_reference>
    <citation>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 with cerebral palsy: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2004 Mar 23;62(6):851-63. doi: 10.1212/01.wnl.0000117981.35364.1b.</citation>
    <PMID>15037681</PMID>
  </results_reference>
  <results_reference>
    <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):1549-62. doi: 10.1016/j.jcyt.2013.06.001. Epub 2013 Oct 5.</citation>
    <PMID>24100132</PMID>
  </results_reference>
  <results_reference>
    <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. doi: 10.1634/stemcells.21-1-105.</citation>
    <PMID>12529557</PMID>
  </results_reference>
  <results_reference>
    <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.</citation>
    <PMID>24909743</PMID>
  </results_reference>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>December 3, 2018</study_first_submitted>
  <study_first_submitted_qc>January 3, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 8, 2019</study_first_posted>
  <last_update_submitted>January 3, 2019</last_update_submitted>
  <last_update_submitted_qc>January 3, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 8, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Tehran University of Medical Sciences</investigator_affiliation>
    <investigator_full_name>Mahmoud Reza Ashrafi</investigator_full_name>
    <investigator_title>Professor of Pediatric Neurology</investigator_title>
  </responsible_party>
  <keyword>Quadriparetic CP, Diparetic CP, Spastic</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Muscle Spasticity</mesh_term>
    <mesh_term>Cerebral Palsy</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 18, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/74/NCT03795974/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03795974
org study id: IRCT201706176907N13
nct id: NCT03795974
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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 .
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 .
allocation: Randomized
intervention model: Parallel Assignment
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
masking: Triple (Participant, Care Provider, Outcomes Assessor)
masking description: only one of the investigators knows the type of cell therapy for intervention group and simulation of intrathecal injection for control group .
measure: Change from baseline Gross Motor Function Classification System (GMFCS)
time frame: Baseline
description: 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 .
measure: Change from baseline Gross Motor Function Classification System (GMFCS)
time frame: "month" 3
description: 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 .
measure: Change from baseline Gross Motor Function Classification System (GMFCS)
time frame: "month" 6
description: 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 .
measure: Change from baseline Gross Motor Function Classification System (GMFCS)
time frame: "month" 12
description: 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 .
measure: Change from baseline GROSS MOTOR FUNCTION MEASURE (GMFM66)
time frame: Baseline
description: 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.
measure: Change from baseline GROSS MOTOR FUNCTION MEASURE (GMFM66)
time frame: "month" 1
description: 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.
measure: Change from baseline GROSS MOTOR FUNCTION MEASURE (GMFM66)
time frame: "month" 3
description: 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.
measure: Change from baseline GROSS MOTOR FUNCTION MEASURE (GMFM66)
time frame: "month" 6
description: 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.
measure: Change from baseline GROSS MOTOR FUNCTION MEASURE (GMFM66)
time frame: "month" 12
description: 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.
measure: Change from baseline Manual Ability Classification System for Children with Cerebral Palsy (MACS)
time frame: Baseline
description: 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.
measure: Change from baseline Manual Ability Classification System for Children with Cerebral Palsy (MACS)
time frame: "month" 3
description: 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.
measure: Change from baseline Manual Ability Classification System for Children with Cerebral Palsy (MACS)
time frame: "month" 6
description: 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.
measure: Change from baseline Manual Ability Classification System for Children with Cerebral Palsy (MACS)
time frame: "month" 12
description: 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.
measure: Change from baseline Pediatric Evaluation of Disability Inventory (PEDI)
time frame: Baseline
description: 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.
measure: Change from baseline Pediatric Evaluation of Disability Inventory (PEDI)
time frame: "month" 6
description: 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.
measure: Change from baseline Pediatric Evaluation of Disability Inventory (PEDI)
time frame: "month" 12
description: 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.
measure: Change from baseline Modified Ashworth scale
time frame: Baseline
description: 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
measure: Change from baseline Modified Ashworth scale
time frame: "month" 1
description: 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
measure: Change from baseline Modified Ashworth scale
time frame: "month" 3
description: 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
measure: Change from baseline Modified Ashworth scale
time frame: "month" 6
description: 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
measure: Change from baseline Modified Ashworth scale
time frame: "month" 12
description: 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
measure: Change from baseline acquired Brain Magnetic Resonance Imaging (MRI) findings
time frame: Baseline
description: 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 .
measure: Change from baseline acquired Brain Magnetic Resonance Imaging (MRI) findings
time frame: "month" 12
description: 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 .
measure: Change from baseline Brain Magnetic Resonance Spectroscopy (MRS)
time frame: Baseline
description: 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.
measure: Change from baseline Brain Magnetic Resonance Spectroscopy (MRS)
time frame: "month" 12
description: 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.
measure: Change from baseline Diffuse Tensor Imaging (DTI) fiber count of periventricular white matter
time frame: Baseline
description: DTI is a modiﬁcation 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 ﬁbers . Periventricular white matter injury is a major form of brain injury observed in CP . Signiﬁcant reduction in DTI ﬁber 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 ﬁber count would be expected due to Stem Cell therapy and will be followed 12 months after injection .
measure: Change from baseline Diffuse Tensor Imaging (DTI) fiber count of periventricular white matter
time frame: "month" 12
description: DTI is a modiﬁcation 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 ﬁbers . Periventricular white matter injury is a major form of brain injury observed in CP . Signiﬁcant reduction in DTI ﬁber 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 ﬁber count would be expected due to Stem Cell therapy and will be followed 12 months after injection .
arm group label: MNC & MSC with Control
arm group type: Active Comparator
description: 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
arm group label: MNC & MSC
arm group type: Experimental
description: Comparison of effects of intrathecal injection of MNC and MSC on improvement of developmental functions and spasticity of CP patients
intervention type: Biological
intervention name: MNC
description: Hematopoietic stem cells derived from allogenic umbilical cord
arm group label: MNC & MSC
arm group label: MNC & MSC with Control
other name: Hematopoietic stem cells
intervention type: Biological
intervention name: MSC
description: Mesenchymal cells derived from allogenic umbilical cord
arm group label: MNC & MSC
arm group label: MNC & MSC with Control
other name: Mesenchymal stem cells
intervention type: Procedure
intervention name: Control
description: control group without injection and appearance simulating lumbar puncture without awareness of the patients and evaluators , but rehabilitation continued .
arm group label: MNC & MSC with Control
criteria: 
gender: All
minimum age: 4 Years
maximum age: 14 Years
healthy volunteers: No
last name: Mahmoudreza Ashrafi, MD
role: Principal Investigator
affiliation: Tehran University of Medical Sciences, Children's Medical Center
last name: Amirali Hamidieh, MD
role: Study Director
affiliation: Tehran University of Medical Sciences , Children's Medical Center
last name: Hadi Montazerlotfelahi, MD
role: Study Director
affiliation: Alborz University of Medical Sciences
last name: Anahita Majma, MD
role: Study Director
affiliation: Tehran University of Medical Sciences Children's Medical Center
last name: Masood Ghahvechi akbari, MD
role: Study Director
affiliation: Tehran University of Medical Sciences ,Children's Medical Center
last name: Ali Reza Moaeidi, MD
role: Study Director
affiliation: Hormozgan University of Medical Sciences
facility: 
facility: 
facility: 
facility: 
country: Iran, Islamic Republic of
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PMID: 21335665
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.
PMID: 26236347
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PMID: 16049045
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 safety. Cytotherapy. 2015 Feb;17(2):232-41. doi: 10.1016/j.jcyt.2014.10.011. Epub 2014 Nov 1.
PMID: 25593079
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. doi: 10.1017/s001216220500112x.
PMID: 16108461
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.
PMID: 19416339
citation: 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 with cerebral palsy: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2004 Mar 23;62(6):851-63. doi: 10.1212/01.wnl.0000117981.35364.1b.
PMID: 15037681
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):1549-62. doi: 10.1016/j.jcyt.2013.06.001. Epub 2013 Oct 5.
PMID: 24100132
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. doi: 10.1634/stemcells.21-1-105.
PMID: 12529557
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.
PMID: 24909743
responsible party type: Principal Investigator
investigator affiliation: Tehran University of Medical Sciences
investigator full name: Mahmoud Reza Ashrafi
investigator title: Professor of Pediatric Neurology
mesh term: Muscle Spasticity
mesh term: Cerebral Palsy
sharing ipd: Undecided
provided document: 