Safety and Efficacy Study of Human ESC-derived Neural Precursor Cells in the Treatment of Parkinson's Disease

Study Overview
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Brief Summary
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This study will evaluate the safety and efficacy of intracerebral transplantation of human embryonic stem cells-derived neural precursor cells in patients with Parkinson's Disease.

Detailed Description
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This study is a Phase I/II, open-label, non randomized clinical trial. The study will enroll 50 patients for cell injection, administering a single dose of neural precursor cells by stereotaxic intra-striatal injection.

Official Title
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A Phase I/II, Open-Label Study to Assess the Safety and Efficacy of Striatum Transplantation of Human Embryonic Stem Cells-derived Neural Precursor Cells in Patients With Parkinson's Disease

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Biological: NPC transplantation
* Drug: Levodopa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary Parkinson's disease patients，a history over 5 years，females or males; Cannot effectively control the PD or tolerate the side effects of drugs; Hoehn and Yahr Stage 3 or 4 in the off state at screening Age between 50 and 80 years; Dopamine is effective or once; Sign the informed consent Exclusion Criteria: Atypical Parkinsonian syndrome or only having tremor syndrome; Having been done pallidotomy, DBS, striatum or extrapyramidal surgery; Subjects are using apomorphine or anticoagulant; Subjects used immunosuppressant or antipsychotic drugs in last 3 months; Subjects used botulinum toxin, phenol, or other drugs for the treatment of dystonia or muscle cramps in last 6 months; During the period of active epilepsy preventing epilepsy with antiepileptic; Coagulant function abnormality or other obviously abnormal laboratory test results; Having skin basal cell carcinoma or cervical cancer and other pre-cancerous lesions; Subject has a history of chronic alcohol or drug abuse ; Pregnancy or lactation; Subjects participated in other clinical trials in recent 3 months; Subject is considered as dementia, a serious mental disorder (depression or mania), and personality or behavioral disorders through cognitive and behavioral test; Cannot cooperate on the research; Severe brain atrophy, or existing brain injury such as cerebral infarction, cerebral vascular malformation or trauma; Severe systemic diseases; Severe dyskinesia or frequent OFF or ON states Severe infectious diseases (eg HIV, HCV, HBV, syphilis positive) Not suitable to participate in this clinical trial assessed by other physicians

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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 |
| --- | --- |
| Experimental: NPC transplantation<br>The patients will receive Levodopa combined with a regular neural precursor cell (NPC) transplantation | Biological: NPC transplantation<br>* The cells are stereotactically implanted in the striatum.<br>Drug: Levodopa<br>* Levodopa is used depending on the patient's condition<br>|
| Experimental: HLA-matched NPC transplantation<br>The patients will receive Levodopa combined with a HLA-matched neural precursor cell (NPC) transplantation | Biological: NPC transplantation<br>* The cells are stereotactically implanted in the striatum.<br>Drug: Levodopa<br>* Levodopa is used depending on the patient's condition<br>|
| Experimental: HLA-non-matched NPC transplantation<br>The patients will receive Levodopa combined with a HLA-non-matched neural precursor cell (NPC) transplantation | Biological: NPC transplantation<br>* The cells are stereotactically implanted in the striatum.<br>Drug: Levodopa<br>* Levodopa is used depending on the patient's condition<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events (TEAEs), severe TEAEs as assessed by head MRI and blood examination | Number of subjects with adverse events such as the evidence of graft failure or rejection | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Unified Parkinson's Disease Rating Scale (UPDRS) score from baseline | The total Unified Parkinson's Disease Rating Scale (UPDRS) score is derived from Part I (Mentation, Behavior and Mood), Part II (Activities of Daily Living) and Part III (Motor Examination). Part I assesses 4 functions; Part II assesses 13 activities of daily living; Part III assesses 14 motor symptoms. Each item is rated on a scale from 0 (normal) to 4 (severe). The minimum total score possible is 0 and the maximum total score possible is 176. Each subject was independently rated by two observers at each study visit and a mean score was calculated for analysis. | Baseline and 12 months | 
| Change in DATscan from baseline | DATscan is an imaging technology that uses small amounts of a radioactive drug to help determine how much dopamine is available in a person's brain.Its principle is based on using of radiopharmaceutical, which bind to dopamine transporters (DAT). | Baseline and 12 months | 
| Change in Hoehn and Yahr Stage from baseline | The Hoehn and Yahr scale is a commonly used system for describing how the symptoms of Parkinson's disease progress mainly by observing balance and walk. | Baseline and 12 months |