Precise Transplantation of Human Amniotic Epithelial Stem Cells Into Lateral Ventricle for Parkinson's Disease

Study Overview
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Brief Summary
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This is a single-center, single-arm, dose escalation study, to explore the safety, tolerability and efficacy of human amniotic epithelial stem cells (hAESCs) for idiopathic Parkinson's disease (PD).

Detailed Description
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hAESCs will be administration through the Ommaya reservoir implanted into the lateral ventricle of subjects with idiopathic PD. This dose escalation will be followed by an exploratory expansion phase in 3 cohorts. Dose A (5×10^7 cells/dose) Dose B (1.0×10^8 cells/dose) Dose C (1.5×10^8 cells/dose).

Official Title
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Precise Transplantation of Human Amniotic Epithelial Stem Cells Into Lateral Ventricle for Parkinson's Disease

Conditions
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Idiopathic Parkinson's Disease

Intervention / Treatment
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* Biological: hAESCs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 40-70 years old, with more than 5 years of idiopathic PD history UPDRS-III off-time scores ≤49 MMSE scores ≥24 HAMD-17 scores < 25 H-Y on-time scores ≤4 reactive to levodopa or dopa agonists PD medication dose is stable for more than 2 months no general anesthesia contraindications, no stereotactic surgery contraindications or other conditions that interfere with clinical evaluation no abnormalities affecting cell transplantation by cranial MRI no participation of other clinical trials 3 months before signing the informed consent Exclusion Criteria: secondary PD or Parkinson's syndrome subcutaneous apomorphine treatment scoring ≥ 2 on UPDRS-I item 2, or ≥ 2 on UPDRS-II item 13; or ≥ 3 on UPDRS-II item14 history of intracranial surgery or device implantation, including deep brain stimulation, within 2 years prior to signing informed consent history of seizures or prophylactic application of antiepileptic drugs other serious central nervous system disorders history of stem cell therapy subject who had undergone a major surgery within 3 months and will undergo a major surgery within the next 6 months prior to signing informed consent autoimmune disease or current use of Immunosuppressants subjects with comorbid cardiac disease, for example, but not limited to, ischemic heart disease, congestive heart failure, significant arrhythmias or cardiac conduction block poorly controlled hypertension, diabetes mellitus, or comorbid endocrine system disorders, pulmonary disorders, gastrointestinal system disorders, serious infections, malignancies, etc. positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies, human immunodeficiency virus (HIV) antibodies, or Treponema pallidum antibody abnormalities in liver or kidney function tests, including alanine aminotransferase (ALT), aspartate aminotransferase (AST) is less than 2.5 times the upper limit of normal, blood urea nitrogen (BUN) or creatinine(Cr) are less than 1.5 times the upper limit of normal, or serum albumin < 30.0 g/L abnormalities in hematologic test: coagulation disorders or ongoing anticoagulation therapy; moderate to severe anemia; platelet count < 80 × 10^9/L inability to undergo MRI and positron emission tomography (PET) examinations subject with severe allergies women of childbearing potential (WOCBP) or subject is a man with a WOCBP partner, who are unwilling to take contraception during the trial pregnant or lactating females other conditions deemed by the investigator to be inappropriate for enrollment.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: hAESCs treatment<br>hAESCs will be administration through Ommaya reservoir implanted into the lateral ventricle. The tolerability, safety, and efficacy will be examined of 4 monthly doses of hAESCs for 3 months followed by 2 doses every 3 months in dose escalation through 3 cohorts. Dose A (5×10^7 cells/dose) Dose B (1.0×10^8 cells/dose) Dose C (1.5×10^8 cells/dose). | Biological: hAESCs<br>* human Amniotic Epithelial Stem Cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicity (DLT) | The occurrence of DLT. | 12 months | 
| Number of participants with adverse event (AE), serious adverse event(SAE) and adverse events of special interest (AESI) | According to CTCAE V5.0, AE, SAE and AESI evaluated by laboratory examination, measurement of vital signs, physical examination, and subjects' symptoms to detect new abnormalities and/or deterioration of previous conditions. AESI is defined as intracranial infection, hemorrhage, rejection, edema, as well as acute allergic reactions and ectopic mass formation associated with the therapy. | 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the UPDRS-III (Unified Parkinson's Rating Scale part III/motor part) scores | UPDRS is used for evaluating the impairment and disability associated with PD. It consists of 4 sections: I Mentation, behavior, and mood; II Activities of daily living (ADLs); III Motor; and IV Complications.The UPDRS score ranges from 0 to 199, with higher score indicating greater disability | 12 months | 
| Change from baseline in the UPDRS off-time total scores | UPDRS is used for evaluating the impairment and disability associated with PD. It consists of 4 sections: I Mentation, behavior, and mood; II Activities of daily living (ADLs); III Motor; and IV Complications.The UPDRS score ranges from 0 to 199, with higher score indicating greater disability | 12 months | 
| Change from baseline in the UPDRS on-time total scores | UPDRS is used for evaluating the impairment and disability associated with PD. It consists of 4 sections: I Mentation, behavior, and mood; II Activities of daily living (ADLs); III Motor; and IV Complications.The UPDRS score ranges from 0 to 199, with higher score indicating greater disability | 12 months | 
| Change from baseline in sum of the UPDRS-II and UPDRS-III scores | UPDRS is used for evaluating the impairment and disability associated with PD. It consists of 4 sections: I Mentation, behavior, and mood; II Activities of daily living (ADLs); III Motor; and IV Complications.The UPDRS score ranges from 0 to 199, with higher score indicating greater disability | 12 months | 
| Changes from baseline in the Parkinson's Disease Questionnaire (PDQ-39) scores | The PDQ-39 is a self-completed questionnaire assessing how often people with Parkinson's experience difficulties across 8 dimensions of daily living with 39 questions . Questions are answered using a 5-point ordinal scoring system: 0 = never, 1 = occasionally, 2 = sometimes, 3 = often, 4 = always. Each scores range from 0 = never have difficulty to 100 = always have difficulty.The higher the score, the lower the quality of life of PD patients. | 12 months | 
| Changes in the Hamilton Depression-17 (HAMD-17) Scale scores | The HAMD-17 Scale is the most widely used scale in clinical evaluation of depression in PD patients. This project takes 8 points as the critical value of depression, and the total score over 35 points is considered as severe depression, more than 20 points is likely to be diagnosed with depression, less than 8 points is not depressed. | 12 months | 
| Change from baseline in the Parkinson's Disease Sleep Scale (PDSS) scores | The PDSS is a visual analogue scale addressing 15 commonly reported symptoms associated with sleep disturbance overall quality of night's sleep (item 1), sleep onset and maintenance insomnia (items 2 and 3), nocturnal restlessness (items 4 and 5), nocturnal psychosis (items 6 and 7), nocturia (items 8 and 9), nocturnal motor symptoms (items 10-13), sleep refreshment (item 14) and daytime dozing (item 15). Scores range from 0 (poorly or often) to 10 (very good or never), with a total score of <90 indicating sleep disturbance, with higher scores indicating better sleep quality. | 12 months | 
| Changes from baseline in the Hoehn and Yahr scale (H-Y) | The Hoehn and Yahr scale is used to provide a general estimate of clinical function of PD patients, combining functional deficits (disability) and objective signs (impairment). The Hoehn and Yahr score ranges from 0 to 5, with higher score indicating higher dysfunction of PD patients. | 12 months | 
| Changes from baseline in the Mini-Mental State Examination (MMSE) | The total score of tne MMSE ranges from 0 to 30, with a higher score indicating better function for Cognitive assessment. | 12 months |