Cerebral Palsy, SpasticPhase 2NCT03795974
Efficacy of Allogeneic Umbilical Cord Derived Hematopoietic and Mesenchymal Stem Cells in Cerebral Palsy
A Phase 2 study testing MNC and MSC in people with Cerebral Palsy, Spastic, run by Tehran University of Medical Sciences at 4 sites in Iran.
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… Read more about this study
- Who is it for?
- Ages 4 to 14 years
- Conditions the study is for
- Cerebral Palsy, Spastic
- What is being tested?
- MNC and MSC
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 108 participants
- Where
- 4 sitesIran
- Study dates
- 23 Jul 2017to Dec 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 14 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
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- Hemorrhagic diathesis
- Severe anemia ( Hemoglobin less than 8 g/dl )
- Ventilator dependent pulmonary diseases
- Renal insufficiency
- Severe liver dysfunction
Trial locations and contacts
4 sites in 1 country.
Iran4 sites
Tehran University of Medical Sciences , Growth and Development Research Center- Children's Medical Center
Tehran, 1419733151
Tehran University of Medical Sciences Chidren's Medical Center Radiology Department
Tehran, 1419733151
Tehran University of Medical Sciences, Department of Pediatric Neurology , Children's Medical Center
Tehran, 1419733151
ROYAN Stem Cell Technology Co
Tehran, 1665666311
About this study
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
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 .
Read the detailed description
CP is characterized by aberrant control of movement or posture of a patient , appearing early in life , and not the result of a recognized progressive or degenerative brain disease . CP is an umbrella term and represents a group of conditions (not a single disorder) , has a broad range of expression with a static condition originally within the developing central nervous system . CP Is a disturbance of movement and or posture . At the present time there is no standard medical or surgical treatment for it .Stem cell therapy is a new and promising treatment .
150 cases of diparetic and quadiparetic spastic CP between 4-14 years old selected among the patients referred to the pediatric neurology outpatient department of Children's Medical Center Hospital (CMC) affiliated to Tehran University of Medical Sciences and had our inclusion criteria. HLA analysis were done for these patients and 36 cases of class 6 matched cases enrolled to the hematopoietic stem cells derived from allogenic umbilical cord (MNC) because of necessity of Human Leukocyte Antigen (HLA) matching in this type of cells and 72 cases among the remaining patients randomly divided to Mesenchymal stem cells derived from allogenic umbilical cord (MSC) and control group . Therefore 108 cases enrolled in 3 divided group of 36 patients .
Patients admitted to CMC hospital and intrathecal injection were done with sedation . Only one injection of stem cell was done for each patient . In the control group after insertion of the needle into the skin with an appearance of lumbar puncture simulation , no injection were done without the awareness of the patients or their parents. All of the patients admitted for one day and discharged the next day . As we wrote in the consent form for ethical consideration we are committed to perform stem cell injection for control participants free of charge after 12 months of the follow up . All of the participants will be referred for neurorehabilitation with a identical protocol .Both parents and clinical evaluators are not aware of the 3 divided groups and our study is double blind .Outcome measures will be evaluated 1, 3, 6. and 12 months after intervention .
Standard brain Magnetic Resonance Imaging (MRI) with Magnetic Resonance Spectroscopy (MRS) and Diffusion Tensor Imaging (DTI) were done before injection as baseline and will be repeated after 12 months of clinical follow up . This study designed for the evaluation of therapeutic effects of intrathecal MNC and MSC derived from allogenic umbilical cord in change and probable improvement of developmental functions of spastic CP patients between 4-14 years old in comparison with control group .Different scoring systems such as Gross Motor Functional Classification System (GMFCS) , Gross Motor Function Measure Score (GMFM66) , Manual Ability Classification System (MACS) , Pediatric Evaluation of Disability Inventory (PEDI) , CP QOL , Life Habits Questionnaire and Modified Ashworth scale for spasticity were done at baseline and then will be repeated in follow ups until 12 months of final evaluation .
Acute side effects and probable long term side effects will be reported and noted on our preformed questioners .
- Conditions
- Cerebral Palsy, Spastic
- Being tested
- MNC, MSC, Control
- Keywords
- Quadriparetic CP, Diparetic CP, Spastic
- Medical subject headings
- Cerebral Palsy, Muscle Spasticity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MNCBiological
Also called Hematopoietic stem cells
Hematopoietic stem cells derived from allogenic umbilical cord
MSCBiological
Also called Mesenchymal stem cells
Mesenchymal cells derived from allogenic umbilical cord
ControlProcedure or surgery
control group without injection and appearance simulating lumbar puncture without awareness of the patients and evaluators , but rehabilitation continued .
| Study group | Role | What they receive |
|---|---|---|
| MNC & MSC with Control | Active comparator | 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 Receives: Biological: MNC; Biological: MSC; Procedure: Control |
| MNC & MSC | Experimental | Comparison of effects of intrathecal injection of MNC and MSC on improvement of developmental functions and spasticity of CP patients Receives: Biological: MNC; Biological: MSC |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 .
Measured: Baseline
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 .
Measured: "month" 3
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 .
Measured: "month" 6
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 .
Measured: "month" 12
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.
Measured: Baseline
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.
Measured: "month" 1
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.
Measured: "month" 3
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.
Measured: "month" 6
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.
Measured: "month" 12
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.
Measured: Baseline
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.
Measured: "month" 3
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.
Measured: "month" 6
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.
Measured: "month" 12
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.
Measured: Baseline
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.
Measured: "month" 6
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.
Measured: "month" 12
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
Measured: Baseline
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
Measured: "month" 1
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
Measured: "month" 3
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
Measured: "month" 6
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
Measured: "month" 12
Secondary outcomes (6)
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 .
Measured: Baseline
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 .
Measured: "month" 12
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.
Measured: Baseline
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.
Measured: "month" 12
Change from baseline Diffuse Tensor Imaging (DTI) fiber count of periventricular white matter
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 .
Measured: Baseline
Change from baseline Diffuse Tensor Imaging (DTI) fiber count of periventricular white matter
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 .
Measured: "month" 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2019
- Study start23 Jul 2017
- Primary completionOct 2019 (estimated)
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Cerebral Palsy, SpasticStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 .
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 108 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tehran University of Medical Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Hormozgan University of Medical Sciences
- Responsible party
- Principal investigator, Mahmoud Reza Ashrafi, Tehran University of Medical Sciences
- Investigators
- Mahmoudreza Ashrafi, MD, Principal investigator, Tehran University of Medical Sciences, Children's Medical CenterAmirali Hamidieh, MD, Study director, Tehran University of Medical Sciences , Children's Medical CenterHadi Montazerlotfelahi, MD, Study director, Alborz University of Medical SciencesAnahita Majma, MD, Study director, Tehran University of Medical Sciences Children's Medical CenterMasood Ghahvechi akbari, MD, Study director, Tehran University of Medical Sciences ,Children's Medical CenterAli Reza Moaeidi, MD, Study director, Hormozgan University of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03795974
- Sponsor's protocol ID
- IRCT201706176907N13
- Status last verified
- Jan 2019
- First submitted
- 3 Dec 2018
- Last updated
- 8 Jan 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 21335665Feng 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.
PubMed 26236347Thomas 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.
PubMed 16049045Zali 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.
PubMed 25593079Bax 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.
PubMed 16108461Shevell 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.
PubMed 19416339Ashwal 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 [RETIRED]: 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.
PubMed 15037681Wang 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.
PubMed 24100132Romanov 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.
PubMed 12529557Crompton 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.
PubMed 24909743Jameie M, Pak N, Mozafar M, Farazmand H, Khodadoust E, Majmaa A, Amanollahi M, Zarrabi M, Nouri M, Ghahvechi Akbari M, Moaiedi AR, Shervin Badv R, Vosough M, Hamidieh AA, Montazerlotfelahi H, Tavasoli AR, Heidari M, Masoomi S, Zamani F, Ashrafi MR. Impact of stem cell therapy on brain metabolic profile in cerebral palsy assessed by magnetic resonance spectroscopy in a randomized clinical trial. Sci Rep. 2026 May 19. doi: 10.1038/s41598-026-50051-x. Online ahead of print.
PubMed 42156830Zarrabi M, Akbari MG, Amanat M, Majmaa A, Moaiedi AR, Montazerlotfelahi H, Nouri M, Hamidieh AA, Badv RS, Karimi H, Rabbani A, Mohebbi A, Rahimi-Dehgolan S, Rahimi R, Dehghan E, Vosough M, Abroun S, Shamsabadi FM, Tavasoli AR, Alizadeh H, Pak N, Zamani GR, Mohammadi M, Javadzadeh M, Ghofrani M, Hassanpour SH, Heidari M, Taghdiri MM, Mohseni MJ, Noparast Z, Masoomi S, Goudarzi M, Mohamadpour M, Shodjaee R, Samimi S, Mohammad M, Gholami M, Vafaei N, Koochakzadeh L, Valizadeh A, Malamiri RA, Ashrafi MR. The safety and efficacy of umbilical cord blood mononuclear cells in individuals with spastic cerebral palsy: a randomized double-blind sham-controlled clinical trial. BMC Neurol. 2022 Mar 29;22(1):123. doi: 10.1186/s12883-022-02636-y.
PubMed 35351020Amanat M, Majmaa A, Zarrabi M, Nouri M, Akbari MG, Moaiedi AR, Ghaemi O, Zamani F, Najafi S, Badv RS, Vosough M, Hamidieh AA, Salehi M, Montazerlotfelahi H, Tavasoli AR, Heidari M, Mohebi H, Fatemi A, Garakani A, Ashrafi MR. Clinical and imaging outcomes after intrathecal injection of umbilical cord tissue mesenchymal stem cells in cerebral palsy: a randomized double-blind sham-controlled clinical trial. Stem Cell Res Ther. 2021 Aug 6;12(1):439. doi: 10.1186/s13287-021-02513-4.
PubMed 34362453
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03795974
- Acronym / sponsor ID
- IRCT201706176907N13
- Conditions
- Cerebral Palsy, Spastic
- Keywords
- Quadriparetic CP, Diparetic CP, Spastic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 108 participants (actual)
- Lead sponsor
- Tehran University of Medical SciencesUniversity, hospital or other
- Collaborators
- Hormozgan University of Medical Sciences
- Study start
- 23 Jul 2017 (actual)
- Primary completion
- Oct 2019 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 8 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cerebral palsy(CP) consisted of a group of developmental disability in the field of motor function and is one of the major problems of pediatric neurology and at the present time there is no standard curative medical or surgical treatment for it .Stem cell therapy is one of a new and hopeful therapeutic methods of therapy for CP .This double blind study designed for the evaluation of safety and therapeutic effects of intrathecal hematopoietic and mesenchymal stem cells derived from allogenic umbilical cord in change and probable improvement of developmental functions of spastic CP participants between 4-14 years old and comparing with control group of CP participants without cell therapy . 108 cases recruited and randomly divided to 3 groups of 36 cases : hematopoietic stem cells derived from allogenic umbilical cord , Mesenchymal cells derived from allogenic umbilical cord and control group without injection and appearance simulating lumbar puncture without awareness of the patients and evaluators . Developmental functions and spasticity evaluated before intervention and will be done 1 , 3 , 6 and 12 months after injection . During this period neuro rehabilitation will be continued . Brain neuroimaging were done at the recruitment time and will be repeated after 12 months .
Detailed description
CP is characterized by aberrant control of movement or posture of a patient , appearing early in life , and not the result of a recognized progressive or degenerative brain disease . CP is an umbrella term and represents a group of conditions (not a single disorder) , has a broad range of expression with a static condition originally within the developing central nervous system . CP Is a disturbance of movement and or posture . At the present time there is no standard medical or surgical treatment for it .Stem cell therapy is a new and promising treatment .
150 cases of diparetic and quadiparetic spastic CP between 4-14 years old selected among the patients referred to the pediatric neurology outpatient department of Children's Medical Center Hospital (CMC) affiliated to Tehran University of Medical Sciences and had our inclusion criteria. HLA analysis were done for these patients and 36 cases of class 6 matched cases enrolled to the hematopoietic stem cells derived from allogenic umbilical cord (MNC) because of necessity of Human Leukocyte Antigen (HLA) matching in this type of cells and 72 cases among the remaining patients randomly divided to Mesenchymal stem cells derived from allogenic umbilical cord (MSC) and control group . Therefore 108 cases enrolled in 3 divided group of 36 patients .
Patients admitted to CMC hospital and intrathecal injection were done with sedation . Only one injection of stem cell was done for each patient . In the control group after insertion of the needle into the skin with an appearance of lumbar puncture simulation , no injection were done without the awareness of the patients or their parents. All of the patients admitted for one day and discharged the next day . As we wrote in the consent form for ethical consideration we are committed to perform stem cell injection for control participants free of charge after 12 months of the follow up . All of the participants will be referred for neurorehabilitation with a identical protocol .Both parents and clinical evaluators are not aware of the 3 divided groups and our study is double blind .Outcome measures will be evaluated 1, 3, 6. and 12 months after intervention .
Standard brain Magnetic Resonance Imaging (MRI) with Magnetic Resonance Spectroscopy (MRS) and Diffusion Tensor Imaging (DTI) were done before injection as baseline and will be repeated after 12 months of clinical follow up . This study designed for the evaluation of therapeutic effects of intrathecal MNC and MSC derived from allogenic umbilical cord in change and probable improvement of developmental functions of spastic CP patients between 4-14 years old in comparison with control group .Different scoring systems such as Gross Motor Functional Classification System (GMFCS) , Gross Motor Function Measure Score (GMFM66) , Manual Ability Classification System (MACS) , Pediatric Evaluation of Disability Inventory (PEDI) , CP QOL , Life Habits Questionnaire and Modified Ashworth scale for spasticity were done at baseline and then will be repeated in follow ups until 12 months of final evaluation .
Acute side effects and probable long term side effects will be reported and noted on our preformed questioners .
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
- 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 .
| Arm | Type | Receives |
|---|---|---|
| MNC & MSC with Control | Active comparator | Biological: MNC, Biological: MSC, Procedure: ControlOne 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 |
| MNC & MSC | Experimental | Biological: MNC, Biological: MSCComparison of effects of intrathecal injection of MNC and MSC on improvement of developmental functions and spasticity of CP patients |
Who may qualify
- Ages
- 4 to 14 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MNCAlso: Hematopoietic stem cellsHematopoietic stem cells derived from allogenic umbilical cord | Biological | MNC & MSC, MNC & MSC with Control |
| MSCAlso: Mesenchymal stem cellsMesenchymal cells derived from allogenic umbilical cord | Biological | MNC & MSC, MNC & MSC with Control |
| Controlcontrol group without injection and appearance simulating lumbar puncture without awareness of the patients and evaluators , but rehabilitation continued . | Procedure or surgery | MNC & MSC with Control |
Primary outcome
Change from baseline Gross Motor Function Classification System (GMFCS)
Time frame: Baseline
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 .
Change from baseline Gross Motor Function Classification System (GMFCS)
Time frame: "month" 3
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 .
Change from baseline Gross Motor Function Classification System (GMFCS)
Time frame: "month" 6
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 .
Change from baseline Gross Motor Function Classification System (GMFCS)
Time frame: "month" 12
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 .
Change from baseline GROSS MOTOR FUNCTION MEASURE (GMFM66)
Time frame: Baseline
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.
Change from baseline GROSS MOTOR FUNCTION MEASURE (GMFM66)
Time frame: "month" 1
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.
Change from baseline GROSS MOTOR FUNCTION MEASURE (GMFM66)
Time frame: "month" 3
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.
Change from baseline GROSS MOTOR FUNCTION MEASURE (GMFM66)
Time frame: "month" 6
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.
Change from baseline GROSS MOTOR FUNCTION MEASURE (GMFM66)
Time frame: "month" 12
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.
Change from baseline Manual Ability Classification System for Children with Cerebral Palsy (MACS)
Time frame: Baseline
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. 1. Handle objects easily and successfully 2. Handles most objects but with somewhat reduced quality and/or speed of achievement 3. Handle objects with difficulty; needs help to prepare and/or modify activities 4. Handles a limited selection of easily managed objects in adapted situations 5. 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.
Change from baseline Manual Ability Classification System for Children with Cerebral Palsy (MACS)
Time frame: "month" 3
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. 1. Handle objects easily and successfully 2. Handles most objects but with somewhat reduced quality and/or speed of achievement 3. Handle objects with difficulty; needs help to prepare and/or modify activities 4. Handles a limited selection of easily managed objects in adapted situations 5. 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.
Change from baseline Manual Ability Classification System for Children with Cerebral Palsy (MACS)
Time frame: "month" 6
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. 1. Handle objects easily and successfully 2. Handles most objects but with somewhat reduced quality and/or speed of achievement 3. Handle objects with difficulty; needs help to prepare and/or modify activities 4. Handles a limited selection of easily managed objects in adapted situations 5. 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.
Change from baseline Manual Ability Classification System for Children with Cerebral Palsy (MACS)
Time frame: "month" 12
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. 1. Handle objects easily and successfully 2. Handles most objects but with somewhat reduced quality and/or speed of achievement 3. Handle objects with difficulty; needs help to prepare and/or modify activities 4. Handles a limited selection of easily managed objects in adapted situations 5. 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.
Change from baseline Pediatric Evaluation of Disability Inventory (PEDI)
Time frame: Baseline
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.
Change from baseline Pediatric Evaluation of Disability Inventory (PEDI)
Time frame: "month" 6
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.
Change from baseline Pediatric Evaluation of Disability Inventory (PEDI)
Time frame: "month" 12
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.
Change from baseline Modified Ashworth scale
Time frame: Baseline
Scoring (taken from Bohannon and Smith, 1987): 0 No increase in muscle tone 1. 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 2. More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved 3. Considerable increase in muscle tone, passive movement difficult 4. 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
Change from baseline Modified Ashworth scale
Time frame: "month" 1
Scoring (taken from Bohannon and Smith, 1987): 0 No increase in muscle tone 1. 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 2. More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved 3. Considerable increase in muscle tone, passive movement difficult 4. 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
Change from baseline Modified Ashworth scale
Time frame: "month" 3
Scoring (taken from Bohannon and Smith, 1987): 0 No increase in muscle tone 1. 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 2. More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved 3. Considerable increase in muscle tone, passive movement difficult 4. 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
Change from baseline Modified Ashworth scale
Time frame: "month" 6
Scoring (taken from Bohannon and Smith, 1987): 0 No increase in muscle tone 1. 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 2. More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved 3. Considerable increase in muscle tone, passive movement difficult 4. 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
Change from baseline Modified Ashworth scale
Time frame: "month" 12
Scoring (taken from Bohannon and Smith, 1987): 0 No increase in muscle tone 1. 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 2. More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved 3. Considerable increase in muscle tone, passive movement difficult 4. 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
6 secondary outcomes
Change from baseline acquired Brain Magnetic Resonance Imaging (MRI) findings
Time frame: Baseline
Change from baseline acquired Brain Magnetic Resonance Imaging (MRI) findings
Time frame: "month" 12
Change from baseline Brain Magnetic Resonance Spectroscopy (MRS)
Time frame: Baseline
Change from baseline Brain Magnetic Resonance Spectroscopy (MRS)
Time frame: "month" 12
Change from baseline Diffuse Tensor Imaging (DTI) fiber count of periventricular white matter
Time frame: Baseline
Change from baseline Diffuse Tensor Imaging (DTI) fiber count of periventricular white matter
Time frame: "month" 12
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2019.
- Background: PubMed 21335665Papadopoulos 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.
- Background: PubMed 26236347Feng 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.
- Background: PubMed 16049045Thomas 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.
- Results publication: PubMed 25593079Zali 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.
- Results publication: PubMed 16108461Bax 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.
- Results publication: PubMed 19416339Shevell 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.
- Results publication: PubMed 15037681Ashwal 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 [RETIRED]: 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.
- Results publication: PubMed 24100132Wang 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.
- Results publication: PubMed 12529557Romanov 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.
- Results publication: PubMed 24909743Crompton 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.
- Derived from this study: PubMed 42156830Jameie M, Pak N, Mozafar M, Farazmand H, Khodadoust E, Majmaa A, Amanollahi M, Zarrabi M, Nouri M, Ghahvechi Akbari M, Moaiedi AR, Shervin Badv R, Vosough M, Hamidieh AA, Montazerlotfelahi H, Tavasoli AR, Heidari M, Masoomi S, Zamani F, Ashrafi MR. Impact of stem cell therapy on brain metabolic profile in cerebral palsy assessed by magnetic resonance spectroscopy in a randomized clinical trial. Sci Rep. 2026 May 19. doi: 10.1038/s41598-026-50051-x. Online ahead of print.
- Derived from this study: PubMed 35351020Zarrabi M, Akbari MG, Amanat M, Majmaa A, Moaiedi AR, Montazerlotfelahi H, Nouri M, Hamidieh AA, Badv RS, Karimi H, Rabbani A, Mohebbi A, Rahimi-Dehgolan S, Rahimi R, Dehghan E, Vosough M, Abroun S, Shamsabadi FM, Tavasoli AR, Alizadeh H, Pak N, Zamani GR, Mohammadi M, Javadzadeh M, Ghofrani M, Hassanpour SH, Heidari M, Taghdiri MM, Mohseni MJ, Noparast Z, Masoomi S, Goudarzi M, Mohamadpour M, Shodjaee R, Samimi S, Mohammad M, Gholami M, Vafaei N, Koochakzadeh L, Valizadeh A, Malamiri RA, Ashrafi MR. The safety and efficacy of umbilical cord blood mononuclear cells in individuals with spastic cerebral palsy: a randomized double-blind sham-controlled clinical trial. BMC Neurol. 2022 Mar 29;22(1):123. doi: 10.1186/s12883-022-02636-y.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mahmoudreza Ashrafi, MD principal investigator
Tehran University of Medical Sciences, Children's Medical Center
Amirali Hamidieh, MD study director
Tehran University of Medical Sciences , Children's Medical Center
Hadi Montazerlotfelahi, MD study director
Alborz University of Medical Sciences
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MNC and MSC in people with Cerebral Palsy, Spastic, run by Tehran University of Medical Sciences at 4 sites in Iran.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Iran. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline Gross Motor Function Classification System (GMFCS) (time frame: Baseline). The study lists 21 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03795974, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2019.