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IRCT20110628006907N15 IRCT 2020-03-17 Tehran University of Medical Sciences Effects of umbilical cord derived mesenchymal stem cells injection in the treatment of Spinal Muscular Atrophy (SMA) MSCSMA Evaluation of the effectiveness of intrathecal injection of allogeneic umbilical cord derived mesenchymal stem cells in the phenotypic changes of Spinal Muscular Atrophy type I, II and III in comparison with control group, A Clinical trial phase I, II 2020-04-20 anticipated 60 Complete https://irct.ir/trial/45840 interventional Randomization: Randomized, Blinding: Double blinded, Placebo: Used, Assignment: Parallel, Purpose: Treatment, Other design features: First study about intrathecal cell therapy in SMA disease in comparison with control group in IRAN - First study about cell therapy by using of mesenchymal stem cells in SMA disease in IRAN, Randomization description: The patients are randomly allocated using a balanced block randomization technique, into two groups of intervention and control (30 cases of intervention with injection of umbilical cord derived Mesenchymal cells, 10 cases in each type of disease and 30 cases of control group without injection, 10 cases in each type of disease) . Randomization will be done by using of blocks of 6 and 9. All subjects randomly allocated with online randomization software to generate random-number sequences. Coordinator of randomization and clinical evaluators will not be aware of patients of each group , Blinding description: This study is double blind therefore, in the control group after insertion of the needle into the skin with an appearance simulating lumbar puncture, needle will be removed without any injection. This technique will be repeated three times every two weeks, similar to intervention groups. Patients and their parents and clinical evaluators will not be aware of this subject. At the end of the study if safety and effectiveness of cell therapy will be proved in the intervention groups, for the ethical consideration stem cell injections will be performed for control groups . N/A Spinal Muscular Atrophy Type 1-2 3. Intervention 1: Intervention group 1: Type 1 SMA patients that will receive three intrathecal injections of mesenchymal stem cells derived from umbilical cord, prepared by Royan stem cell Technology Company and Cell Thec Pharmed company. Intrathecal injections will be done under anesthesia via lumbar puncture. After taking 2 milliliters of cerebrospinal fluid, 2 milliliters suspension that contains 20 million stem cells will be injected with a syringe. The patient will be admitted for one day of probable adverse reactions monitoring . One year followup and evaluations with regular and similar rehabilitative therapy will be done . Intervention 2: Intervention group 2 : Type 2 SMA patients that will receive three intrathecal injections of mesenchymal stem cells derived from umbilical cord, prepared by Royan stem cell Technology Company and Cell Thec Pharmed company. Intrathecal injections will be done under anesthesia via lumbar puncture. After taking 2 milliliters of cerebrospinal fluid, 2 milliliters suspension that contains 20 million stem cells will be injected with a syringe. The patient will be admitted for one day of probable adverse reactions monitoring . One year followup and evaluations with regular and similar rehabilitative therapy will be done . Intervention 3: Intervention group 3 : Type 3 SMA patients that will receive three intrathecal injections of mesenchymal stem cells, derived from umbilical cord prepared by Royan stem cell Technology Company and Cell Thec Pharmed company. Intrathecal injections will be done under anesthesia via lumbar puncture. After taking 2 milliliters of cerebrospinal fluid, 2 milliliters suspension that contains 20 million stem cells will be injected with a syringe. The patient will be admitted for one day of probable adverse reactions monitoring . One year followup and evaluations with regular and similar rehabilitative therapy will be done . Intervention 4: Control group 1:Type 1 SMA patients that after insertion of needle into the skin, without entrance to cerebrospinal fluid space, needle will be removed without any injection . In this group only intrathecal injection will be simulated, without patients or their parents awareness . The patient will be admitted for one day of probable adverse reactions monitoring . One year followup and evaluations with regular and similar rehabilitative therapy will be done . Intervention 5: Control group 2: Type 2 SMA patients that after insertion of needle into the skin, without entrance to cerebrospinal fluid space, needle will be removed without any injection . In this group only intrathecal injection will be simulated, without patients or their parents awareness . The patient will be admitted for one day of probable adverse reactions monitoring . One year followup and evaluations with regular and similar rehabilitative therapy will be done . Intervention 6: Control group 3:Type 3 SMA patients that after insertion of needle into the skin, without entrance to cerebrospinal fluid space, needle will be removed without any injection . In this group only intrathecal injection will be simulated, without patients or their parents awareness . The patient will be admitted for one day of probable adverse reactions monitoring . One year followup and evaluations with regular and similar rehabilitative therapy will be done . Yes - There is a plan to make this available What will be shared: All collected data deidentified can be shared When: Availability of data starting 6 months after publication,without time limitation To whom: Researchers working in academic institutions and people working in businesses Conditions: Documents will be shared for replication of study in other Medical universities Where to obtain: Email addresses How to obtain: Request by email addresses Comments:
public Morteza Heidari
Children's Medical Center Hospital, No 62, Gharib Street, End of Keshavarz Blvd
Tehran Iran (Islamic Republic of) 1419733151 +98 21 6612 9252 mortezah93@gmail.com Tehran University of Medical Sciences scientific Mahmoud Reza Ashrafi
Children's Medical Center Hospital, No 62, Gharib Street, End of Keshavarz Blvd
Tehran Iran (Islamic Republic of) 1419733151 +98 21 6612 9252 mr_ashrafi@yahoo.com Tehran University of Medical Sciences Iran (Islamic Republic of) Genetically confirmed deletion of SMN1 gene for the diagnosis of SMA disease, SMN2 gene copy number count for the diagnostic classification of disease type, Minimum age of 6 months in type I, Ventilator independent patients at the beginning of treatment in type I, Maximum age of 16 years in type II and III, Ventilator independent patients in type II and III, Absence of brain damage, Absence of liver disease, Absence of renal disease, Absence of hematological disease, Informed consent of patients and their parents 6 months 16 years Both Acquired brain damage including hypoxia, ُStructural and functional brain disorders, Acute infections such as( HCV, HIV,HBV), Malignancies, Hemorrhagic diathesis, Severe anemia ( Hb less than 8 gram/dl), Renal dysfunction, Hepatic dysfunction G12 Spinal muscular atrophy and related syndromes Treatment - Drugs Treatment - Drugs Treatment - Drugs Placebo Placebo Placebo Intervention group 1: Type 1 SMA patients that will receive three intrathecal injections of mesenchymal stem cells derived from umbilical cord, prepared by Royan stem cell Technology Company and Cell Thec Pharmed company. Intrathecal injections will be done under anesthesia via lumbar puncture. After taking 2 milliliters of cerebrospinal fluid, 2 milliliters suspension that contains 20 million stem cells will be injected with a syringe. The patient will be admitted for one day of probable adverse reactions monitoring . One year followup and evaluations with regular and similar rehabilitative therapy will be done . Intervention group 2 : Type 2 SMA patients that will receive three intrathecal injections of mesenchymal stem cells derived from umbilical cord, prepared by Royan stem cell Technology Company and Cell Thec Pharmed company. Intrathecal injections will be done under anesthesia via lumbar puncture. After taking 2 milliliters of cerebrospinal fluid, 2 milliliters suspension that contains 20 million stem cells will be injected with a syringe. The patient will be admitted for one day of probable adverse reactions monitoring . One year followup and evaluations with regular and similar rehabilitative therapy will be done . Intervention group 3 : Type 3 SMA patients that will receive three intrathecal injections of mesenchymal stem cells, derived from umbilical cord prepared by Royan stem cell Technology Company and Cell Thec Pharmed company. Intrathecal injections will be done under anesthesia via lumbar puncture. After taking 2 milliliters of cerebrospinal fluid, 2 milliliters suspension that contains 20 million stem cells will be injected with a syringe. The patient will be admitted for one day of probable adverse reactions monitoring . One year followup and evaluations with regular and similar rehabilitative therapy will be done . Control group 1:Type 1 SMA patients that after insertion of needle into the skin, without entrance to cerebrospinal fluid space, needle will be removed without any injection . In this group only intrathecal injection will be simulated, without patients or their parents awareness . The patient will be admitted for one day of probable adverse reactions monitoring . One year followup and evaluations with regular and similar rehabilitative therapy will be done . Control group 2: Type 2 SMA patients that after insertion of needle into the skin, without entrance to cerebrospinal fluid space, needle will be removed without any injection . In this group only intrathecal injection will be simulated, without patients or their parents awareness . The patient will be admitted for one day of probable adverse reactions monitoring . One year followup and evaluations with regular and similar rehabilitative therapy will be done . Control group 3:Type 3 SMA patients that after insertion of needle into the skin, without entrance to cerebrospinal fluid space, needle will be removed without any injection . In this group only intrathecal injection will be simulated, without patients or their parents awareness . The patient will be admitted for one day of probable adverse reactions monitoring . One year followup and evaluations with regular and similar rehabilitative therapy will be done . Evaluation of effectiveness of umbilical cord derived mesenchymal stem cells in increasing life expectancy of SMA type 1. Timepoint: Before intervention and then every 2 months till 1 year. Method of measurement: Questionnaire and clinical exams. Evaluation of effectiveness of umbilical cord derived mesenchymal stem cells in increasing muscle strength of SMA type 1. Timepoint: Before intervention and then every 2 months till 1 year. Method of measurement: Hammersmith Infant Neurological Examinations (HINE) ,Children's Hospital of Philadelphia Questionnaire (CHOP intent ). Evaluation of effectiveness of umbilical cord derived mesenchymal stem cells in increasing muscle strength of SMA type 2. Timepoint: Before intervention and then every 4 months till 1 year. Method of measurement: Expanded Hammersmith Functional Motor Scale(HFMSE) WHO Motor Mile stones (WMM) questionnaire , Upper limb Module Scale (ULMS). Evaluation of effectiveness of umbilical cord derived mesenchymal stem cells in increasing muscle strength of SMA type 3. Timepoint: Before intervention and then every 4 months till 1 year. Method of measurement: Expanded Hammersmith Functional Motor Scale(HFMSE) WHO Motor Mile stones (WMM) questionnaire, Upper limb Module Scale (ULMS) questionnaire, 6 Minute Walk Test (6MWT). Improvement of Electrodiagnosic evaluative indexes of SMA patients. Timepoint: Before intervention , 2 months after last injection and then every 4 months till 1 year of first injection. Method of measurement: Motor unit number estimation (CMAP scan). Number of participants experiencing adverse effects and serious adverse effects. Timepoint: First 24 hours after injection and then any time if occurred. Method of measurement: Questionnaire , parents report and periodic planned clinical evaluations. ROYAN stem cell technology Co Tehran University of Medical Sciences ROYAN stem cell technology Co Approved 2020-02-04 Tehran University of Medical Sciences No 226, Central organization of Tehran University of Medical Sciences, Ghods Street, Keshavarz Blvd Tehran Tehran Iran (Islamic Republic of)