Protocol summary
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Study aim
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This study designed for the evaluation of safety and therapeutic effects of intrathecal hematopoietic (MNC) and mesenchymal stem cells (MSC) derived from allogenic umbilical cord in change of developmental functions of spastic cerebral Palsy (CP) in comparison with control group .
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Design
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Two arm parallel group , double blind , randomized controlled trial
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Settings and conduct
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108 cases of Spastic CP patients between 4-14 years that have our inclusion criteria will be selected and randomly divided in 3 groups of MNC and MSC derived from umbilical cord and control of no injection .The trial is double blind and the participants and clinical evaluators are unaware of study groups .
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Participants/Inclusion and exclusion criteria
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Inclusion criteria:Diparetic and quadriparetic spastic CP between 4-14 years old and Gross motor function classification ( GMFC) between 2 -5
ٍExclusion criteria : Other types of CP
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Intervention groups
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Intervention group 1: one intrathecal injection(ITI) of MNC . Intervention group 2: one ITI of MSC.
Control group: without injection ,that after insertion of needle into the skin without entrance to CSF space needle withdrawn and only simulation of ITI without the awareness of the participants . All of the participants had a baseline brain neuroimaging , that will be repeated after 12 months . Patients will be evaluated by predicted scales during the 12 months and will be followed for similar rehabilitation protocol .
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Main outcome variables
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Motor development alteration with GMFM 66 score
Change of motor function with GMFCS score
Spasticity change of patients according to Ashworth scale
Developmental status according to Stanford Binet test
General information
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Reason for update
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Acronym
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IRCT registration information
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IRCT registration number:
IRCT201706176907N13
Registration date:
2017-07-12, 1396/04/21
Registration timing:
prospective
Last update:
2019-05-18, 1398/02/28
Update count:
1
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Registration date
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2017-07-12, 1396/04/21
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Registrant information
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Recruitment status
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Recruitment complete
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Funding source
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Tehran University of Medical Sciences , Social welfare organization of Iran,Royan stem cell Technology , Hormozgn University of Medical Sciences, Stem cell iranian science and technolgy institute
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Expected recruitment start date
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2017-11-22, 1396/09/01
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Expected recruitment end date
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2018-10-23, 1397/08/01
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Actual recruitment start date
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empty
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Actual recruitment end date
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empty
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Trial completion date
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empty
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Scientific title
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Evaluation of the efficacy of allogeneic umbilical cord derived hematopoietic and mesenchymal stem cells on developmental functions of spastic cerebral palsy patients between 4-14 years old in comparison with control group , A Clinical trial phase II
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Public title
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Effects of umbilical cord derived stem cells injection in the treatment of children with cerebral palsy
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Purpose
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Treatment
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Inclusion/Exclusion criteria
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Inclusion criteria:
Spastic cerebral palsy (Diparetic , Quadriparetic)
Ages between 4 - 14 years
Gross motor function classification (GMFC) between 2 -5
No seizure disorder or with controlled seizure
Evidence of definite acquired abnormal imaging findings compatible with Cerebral Palsy
Informed consent taken from their parents
Exclusion criteria:
Normal brain MRI
Progressive neurological diseases ( for example leukodystrophy or neurometabolic disorders)
Congenital Cortical malformations
Toxoplasmosis Others Rubella Cytomegalovirus Hepatitis (TORCH) 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)
Hemorrhagic diathesis
Severe anemia ( Hemoglobin less than 8 )
Ventilator dependent pulmonary diseases
Renal insufficiency
Severe liver dysfunction
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Age
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From 4 years old to 14 years old
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Gender
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Both
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Phase
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2
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Groups that have been masked
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- Participant
- Care provider
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Sample size
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Target sample size:
108
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Randomization (investigator's opinion)
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Randomized
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Randomization description
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The patients are randomly allocated into three groups of intervention and control using a balanced block randomization technique. To do that, they were divided into blocks of 6 and 9. All subjects randomly allocated with online randomization software to generate random-number sequences. {Sealed Envelope Ltd. 2015. Create a blocked randomization list. [Online] Available from: https://www.sealedenvelope.com/simple-randomiser/v1/lists [Accessed 15 Dec 2015]}. Coordinator and Physician responsible for assessing inclusion / exclusion criteria and registering individuals are blind.
Due to necessity of HLA matching of hematopoietic stem cells derived from allogenic umbilical cord (MNC) group we selected 150 cases of referred patients with our inclusion criteria and HLA analysis were done for these patients and then 36 cases of class 6 matched patients enrolled to the MNC group 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 .
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Blinding (investigator's opinion)
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Double blinded
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Blinding description
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As this study designed as double blind , In the control group after insertion of the needle into the skin with an appearance of simulation of lumbar puncture no injection were done without the awareness of the patients or their parents and clinical evaluators . at the end of the study if safety and effectiveness of cell therapy will be proved , for ethical consideration cell therapy will be performed for control group .
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Placebo
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Not used
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Assignment
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Parallel
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Other design features
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For the first time in our country , intrathecal injection of mesenchymal stem cells derived from umbilical cord for the treatment of CP applied .
Secondary Ids
1
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Registry name
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Clinical trials.gov
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Secondary trial Id
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NCT03795974
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Registration date
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2019-01-08, 1397/10/18
Ethics committees
1
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Ethics committee
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Approval date
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2017-06-06, 1396/03/16
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Ethics committee reference number
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IR.TUMS.VCRREC.1996.2506
Health conditions studied
1
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Description of health condition studied
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Spastic Cerebral Palsy
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ICD-10 code
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G80.9
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ICD-10 code description
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Cerebral Palsy , Unspecified
Primary outcomes
1
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Description
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Motor development alteration with GMFM 66 score
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Timepoint
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Before intervention , 1 month after intervention , 3 months after intervention ,6 months after intervention , 12 months after intervention
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Method of measurement
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questionairre
2
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Description
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Change of motor function with GMFCS score
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Timepoint
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Before intervention , 1 month after intervention , 3 months after intervention ,6 months after intervention , 12 months after intervention
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Method of measurement
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questionairre
3
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Description
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Spasticity change of patients according to Ashworth scale
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Timepoint
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Before intervention , 1 month after intervention , 3 months after intervention ,6 months after intervention , 12 months after intervention
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Method of measurement
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questionairre
4
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Description
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Developmental status according to Stanford Binet test
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Timepoint
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Before intervention , 1 month after intervention , 3 months after intervention ,6 months after intervention , 12 months after intervention
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Method of measurement
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questionairre
Secondary outcomes
1
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Description
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Probable Change of brain lesions
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Timepoint
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Before intervention , 1 year after intervention
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Method of measurement
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Brain Magnetic Resonance Imaging (MRI) , Brain Magnetic Resonance Spectroscopy (MRS) , Brain Deep Tensor Imaging (DTI)
2
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Description
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Fever
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Timepoint
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24 hours after intervention , 48 hours after intervention , 72 hours after intervention
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Method of measurement
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Axillary thermometer
3
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Description
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Meningitis
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Timepoint
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First 3 days after intervention or any time after intervention
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Method of measurement
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Lumbar Puncture
4
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Description
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Hyper sensitivity reactions
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Timepoint
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First week after intervention
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Method of measurement
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Physical exam
Intervention groups
1
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Description
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Intervention group 1 one intrathecal injection of hematopoietic stem cell derived from umbilical cord ( 5 millions per Kg ) prepared by Royan stem cell Technology Company . Intrathecal injection will be done under anesthesia via lumbar puncture . After taking 5 milliliter of cerebrospinal fluid prepared stem cells will be injected with a syringe . The patient will be admitted for one day of probable adverse reaction observation . One year followup and evaluation with regular similar rehabilitative therapy will be done .
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Category
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Treatment - Drugs
2
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Description
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Intervention group 2 one intrathecal injection of mesenchymal stem cellls derived from umbilical cord ( 1 million per kg) prepared by Cell Thec Pharmed Company. Intrathecal injection will be done under anesthesia via lumbar puncture . After taking 5 milliliter of cerebrospinal fluid prepared stem cells will be injected with a syringe . The patient will be admitted for one day of probable adverse reaction observation . One year followup and evaluation with regular similar rehabilitative therapy will be done .
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Category
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Treatment - Drugs
3
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Description
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Control group without injection , that after insertion of needle into the skin without entering into the cerebrospinal fluid space , needle will be withdrawn without any injection and only with an appearance of simulation of lumbar puncture without the awareness of the patient or their parents. The patient will be admitted for one day of probable adverse reaction observation . One year followup and evaluation with regular similar rehabilitative therapy will be done .
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Category
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Treatment - Other
1
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Sponsor
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Grant name
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Grant code / Reference number
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Is the source of funding the same sponsor organization/entity?
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Yes
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Title of funding source
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Tehran University of Medical Sciences
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Proportion provided by this source
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40
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Public or private sector
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Public
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Academic
2
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Sponsor
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Grant name
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Grant code / Reference number
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Is the source of funding the same sponsor organization/entity?
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Yes
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Title of funding source
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ROYAN stem cell technology Co
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Proportion provided by this source
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30
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Public or private sector
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Private
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Industry
3
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Sponsor
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Grant name
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Grant code / Reference number
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Is the source of funding the same sponsor organization/entity?
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Yes
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Title of funding source
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Welfare Organization of Iran
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Proportion provided by this source
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20
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Public or private sector
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Public
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Other
4
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Sponsor
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Grant name
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Grant code / Reference number
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Is the source of funding the same sponsor organization/entity?
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Yes
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Title of funding source
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Hormozgan University of Medical Sciences
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Proportion provided by this source
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10
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Public or private sector
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Public
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Academic
Sharing plan
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Deidentified Individual Participant Data Set (IPD)
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Yes - There is a plan to make this available
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Study Protocol
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Yes - There is a plan to make this available
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Statistical Analysis Plan
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Undecided - It is not yet known if there will be a plan to make this available
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Informed Consent Form
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Yes - There is a plan to make this available
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Clinical Study Report
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Yes - There is a plan to make this available
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Analytic Code
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No - There is not a plan to make this available
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Data Dictionary
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Not applicable
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Title and more details about the data/document
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IPD collected for the primary outcomes and secondary outcome measures
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When the data will become available and for how long
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Dec 2019
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To whom data/document is available
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people working in academic institutions , people working in businesses and patients
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Under which criteria data/document could be used
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Publications of study
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From where data/document is obtainable
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Contact persons
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What processes are involved for a request to access data/document
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Telephone or email
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Comments
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