A New Method to Treat Hereditary Cerebellar Ataxia - Umbilical Cord Mesenchymal Stem Cells Transplantation

Study Overview
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Brief Summary
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Hereditary cerebellar ataxia is a type of autosomal dominant genetic disease, lesions mainly involving the cerebellum, but the spinal cord and cranial nerves may also be some involvement. A total of 20 molecularly diagnosed SCA1 patients divided in two groups. One group accepted for the treatment of stem cell transplantation,the other group will be the control. Purpose of this project to prove that allogeneic umbilical cord mesenchymal stem cells are applied to clinical safely, and in the treatment of hereditary cerebellar ataxia is valid.

Detailed Description
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After admission the patients accepted transplantation would receive physical examination, blood and urine tests, electrocardiogram, electrophysiologic study;evaluation of SCA1 symptoms (balance, walking, dexterity, tremor, memory, mood and concentration),then stem cell therapy：after stem cell prepared, the patients accepted 4 times stem cell transplantations through lumbar puncture, the time is 3-5days between two treatments. The control only receive evaluation of SCA1 symptoms .

Official Title
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The Safety and Efficacy of Umbilical Cord Mesenchymal Stem Cells Transplantation in Hereditary Cerebellar Ataxia Patients

Conditions
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Hereditary Cerebellar Ataxia.

Intervention / Treatment
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* Other: stem cell transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-65 years of age Molecularly diagnosed SCA1 Exclusion Criteria: Cognitively impaired individuals Schizophrenics Patients with severe kidney and liver disease, epilepsy, heart disease, pulmonary disease, cardiac arrhythmia, diabetes insipidus, leukemia and some other central neural disease (such as Parkinson disease, accidence of brain vascular et al) Age less than 18 years, age greater than 65 years

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control group<br>Ten patients in the group only receive nerve functional evaluation and electrophysiology examination before and 1,3,6,12 months after recruit. They will not accept cell therapy. | |
| Experimental: Stem cell transplantation<br>10 patients in the group accept stem cell transplantation. | Other: stem cell transplantation<br>* The patients accepted 4 times stem cell transplantations through lumbar puncture, the time is 3-5days between two treatments and the dose is about 2 ml(including 1×10'7 cells).<br>* Other names: Cell therapy.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| blood test | white blood cell、neutrophilic granulocyte、leukomonocyte；glutamic pyruvic transaminase(GPT)、glutamic oxalacetic transaminase、lactate dehydrogenase(LDH)、;hydroxybutyrate dehydrogenase(HBDH)、phosphocreatine kinase(CK)；acidum uricum(UA)、creatinine(Cr)、α1- microglobulin、β2- microglobulin；lymphotoxin(LCT). Tumor markers(AFP,CEA,CA125,CA15-3,CA19-9,CA72-4CY21-1,NSE) ,Lymphocytes classification | within one week before transplantation | 
| Nerve functional evaluation | Timed-up-and-go test ,5 minutes down-and-up test ICARS score Modified Falls Efficacy Scale Berg balance assessment Tremor Rating Scale: Part A - Tremor location/severity rating Part B -Handwriting and drawings Part C - Functional disabilities resulting from tremor Questionnaires related to sleep, depression (Beck Depression Inventory) (BDI), alertness (Computerized Continuous Performing Tasks) and memory (Mini Mental State Examination) | within one week before transplantation | 
| blood test | white blood cell、neutrophilic granulocyte、leukomonocyte；glutamic pyruvic transaminase(GPT)、glutamic oxalacetic transaminase、lactate dehydrogenase(LDH)、;hydroxybutyrate dehydrogenase(HBDH)、phosphocreatine kinase(CK)；acidum uricum(UA)、creatinine(Cr)、α1- microglobulin、β2- microglobulin；lymphotoxin(LCT). Tumor markers(AFP,CEA,CA125,CA15-3,CA19-9,CA72-4CY21-1,NSE) ,Lymphocytes classification | 1 month after transplantation | 
| blood test | white blood cell、neutrophilic granulocyte、leukomonocyte；glutamic pyruvic transaminase(GPT)、glutamic oxalacetic transaminase、lactate dehydrogenase(LDH)、;hydroxybutyrate dehydrogenase(HBDH)、phosphocreatine kinase(CK)；acidum uricum(UA)、creatinine(Cr)、α1- microglobulin、β2- microglobulin；lymphotoxin(LCT). Tumor markers(AFP,CEA,CA125,CA15-3,CA19-9,CA72-4CY21-1,NSE) ,Lymphocytes classification | 3 months after transplantation | 
| blood test | white blood cell、neutrophilic granulocyte、leukomonocyte；glutamic pyruvic transaminase(GPT)、glutamic oxalacetic transaminase、lactate dehydrogenase(LDH)、;hydroxybutyrate dehydrogenase(HBDH)、phosphocreatine kinase(CK)；acidum uricum(UA)、creatinine(Cr)、α1- microglobulin、β2- microglobulin；lymphotoxin(LCT). Tumor markers(AFP,CEA,CA125,CA15-3,CA19-9,CA72-4CY21-1,NSE) ,Lymphocytes classification | 6 months after transplantation | 
| blood test | white blood cell、neutrophilic granulocyte、leukomonocyte；glutamic pyruvic transaminase(GPT)、glutamic oxalacetic transaminase、lactate dehydrogenase(LDH)、;hydroxybutyrate dehydrogenase(HBDH)、phosphocreatine kinase(CK)；acidum uricum(UA)、creatinine(Cr)、α1- microglobulin、β2- microglobulin；lymphotoxin(LCT). Tumor markers(AFP,CEA,CA125,CA15-3,CA19-9,CA72-4CY21-1,NSE) ,Lymphocytes classification | 12 months after transplantation | 
| Nerve functional evaluation | Timed-up-and-go test ,5 minutes down-and-up test ICARS score Modified Falls Efficacy Scale Berg balance assessment Tremor Rating Scale: Part A - Tremor location/severity rating Part B -Handwriting and drawings Part C - Functional disabilities resulting from tremor Questionnaires related to sleep, depression (Beck Depression Inventory) (BDI), alertness (Computerized Continuous Performing Tasks) and memory (Mini Mental State Examination) | 1 month after transplantation | 
| Nerve functional evaluation | Timed-up-and-go test ,5 minutes down-and-up test ICARS score Modified Falls Efficacy Scale Berg balance assessment Tremor Rating Scale: Part A - Tremor location/severity rating Part B -Handwriting and drawings Part C - Functional disabilities resulting from tremor Questionnaires related to sleep, depression (Beck Depression Inventory) (BDI), alertness (Computerized Continuous Performing Tasks) and memory (Mini Mental State Examination) | 3 months after transplantation | 
| Nerve functional evaluation | Timed-up-and-go test ,5 minutes down-and-up test ICARS score Modified Falls Efficacy Scale Berg balance assessment Tremor Rating Scale: Part A - Tremor location/severity rating Part B -Handwriting and drawings Part C - Functional disabilities resulting from tremor Questionnaires related to sleep, depression (Beck Depression Inventory) (BDI), alertness (Computerized Continuous Performing Tasks) and memory (Mini Mental State Examination) | 6 months after transplantation | 
| Nerve functional evaluation | Timed-up-and-go test ,5 minutes down-and-up test ICARS score Modified Falls Efficacy Scale Berg balance assessment Tremor Rating Scale: Part A - Tremor location/severity rating Part B -Handwriting and drawings Part C - Functional disabilities resulting from tremor Questionnaires related to sleep, depression (Beck Depression Inventory) (BDI), alertness (Computerized Continuous Performing Tasks) and memory (Mini Mental State Examination) | 12 months after transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinal test | proteinum、akaryocyte、α1- microglobulin、β2- microglobulin | within one week before transplantation | 
| Electrophysiology examination | somatosensory evoked potential(SEP)、brain stem auditory evoked potential(BAEP) | within one week before transplantation | 
| Urinal test | proteinum、akaryocyte、α1- microglobulin、β2- microglobulin | 1 month after transplantation | 
| Urinal test | proteinum、akaryocyte、α1- microglobulin、β2- microglobulin | 3 months after transplantation | 
| Urinal test | proteinum、akaryocyte、α1- microglobulin、β2- microglobulin | 6 months after transplantation | 
| Urinal test | proteinum、akaryocyte、α1- microglobulin、β2- microglobulin | 12 months after transplantation | 
| Electrophysiology examination | somatosensory evoked potential(SEP)、brain stem auditory evoked potential(BAEP) | 1 month after transplantation | 
| Electrophysiology examination | somatosensory evoked potential(SEP)、brain stem auditory evoked potential(BAEP) | 3 months after transplantation | 
| Electrophysiology examination | somatosensory evoked potential(SEP)、brain stem auditory evoked potential(BAEP) | 6 months after transplantation | 
| Electrophysiology examination | somatosensory evoked potential(SEP)、brain stem auditory evoked potential(BAEP) | 12 months after transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cerebellar ataxia, hereditary disease, stem cell